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Trial registered on ANZCTR


Registration number
ACTRN12620000402943
Ethics application status
Approved
Date submitted
20/12/2019
Date registered
25/03/2020
Date last updated
27/04/2023
Date data sharing statement initially provided
25/03/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Radiation Therapy With Concomitant and Adjuvant Temozolomide Versus Radiation Therapy With Adjuvant PCV Chemotherapy in Patients With Anaplastic Glioma or Low Grade Glioma
Scientific title
Phase III Intergroup Study of Radiotherapy With Concomitant and Adjuvant Temozolomide Versus Radiotherapy With Adjuvant PCV Chemotherapy in Patients With 1p/19q Co-deleted Anaplastic Glioma or Low Grade Glioma
Secondary ID [1] 299783 0
NCT00887146
Secondary ID [2] 299784 0
NCI-2011-01915
Secondary ID [3] 299785 0
N0577
Universal Trial Number (UTN)
U1111-1243-3114
Trial acronym
CODEL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Brain and Central Nervous System Tumors 315150 0
Condition category
Condition code
Cancer 313466 313466 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The different treatment combinations in this study are radiotherapy plus a drug called temozolomide (both during and following radiation) or radiotherapy followed by a combination of three drugs procarbazine, lomustine and vincristine. At the present time, although both approaches are active treatments in these conditions, we do not know which treatment is best. This is the first study directly comparing the two treatments.
The prescribed radiation dose will be 59.4 Gy, using 1.8 Gy per fractions, 5 fractions per week over 6.5 weeks. The overall treatment time should not exceed 52 days.

Experimental: Arm A (Radiotherapy, procarbazine, lomustine, vincristine) - Patients undergo three-dimensional conformal radiation therapy or Intensity modulated radiation therapy on days 1-5 for 5-7 weeks. Patients also receive procarbazine hydrochloride by mouth on days 8-21, lomustine by mouth on day 1 and vincristine sulfate IV on days 8 and 29 of courses 3-8. Treatment repeats every 6-7 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Experimental: Arm B (Radiotherapy, temozolomide) - Patients undergo radiotherapy as in arm I and receive temozolomide by mouth daily on days 1-5 for 5-7 weeks. Beginning 4 weeks after completion of concurrent chemoradiotherapy, patients receive adjuvant temozolomide by mouth daily days 1-5. Treatment with adjuvant temozolomide repeats every 4 weeks for 6-12 courses in the absence of disease progression and unacceptable toxicity.


Treatment: Drugs: concomitant temozolomide (TMZ)
75 mg/m^2, orally daily

Treatment: Other: radiotherapy


Treatment: Drugs: procarbazine
Days 8-21: 60 mg/m^2 orally

Treatment: Drugs: adjuvant temozolomide (TMZ)
150 or 200 mg/m^2 orally (200mg in the absence of toxicity)

Treatment: Drugs: lomustine
Day 1: 110 mg/m^2 orally

Treatment: Drugs: vincristine
Days 8 and 29: 1.4 mg/m^2 Intravenous
Intervention code [1] 316037 0
Treatment: Drugs
Intervention code [2] 316038 0
Treatment: Other
Comparator / control treatment
At the present time, although both approaches are active treatments in these conditions, we do not know which treatment is best. This is the first study directly comparing the two treatments.
Control group
Active

Outcomes
Primary outcome [1] 321936 0
Progression-free survival - The distribution of progression free survival for Arms A and B will be estimated using the Kaplan-Meier method. The hazard ratios and median progression free survival (PFS) will be estimated with their confidence intervals. The Cox proportional hazards model will be used to assess whether the distributions of progression survival times differ with respect to treatment regimen having adjusted for all stratification factors (cooperative groups, age, and performance score). Both non-inferiority and superiority will be tested in this trial for the primary goal and no multiple-comparison adjustment will be considered. Data to be used for the Kaplan meier method will be sourced from scan results as well as evidence of clinical progression from investigator assessment/medical records.
Timepoint [1] 321936 0
Time from study registration to time of tumor progression or death due to any cause, whichever comes first, assessed up to 16 years
Secondary outcome [1] 376742 0
Time to progression - Estimated by Kaplan-Meier method and analyzed by Cox regression model adjusting all stratification factors. Correlations among baseline neurocognitive test scores and progression free survival will be analyzed using Cox proportional hazards model.
Neurocognitive testing is comprised of:
- Memory (5 minutes): Hopkins Verbal Learning Test – Revised (HVLT-R)
- Fluency (5 minutes):Controlled Oral Word Association test from the Multilingual Aphasia Examination (COWA)
- General Mental Ability (10 minutes): Trail Making Test A and B
- Delayed Memory (5 minutes): Recall and Recognition of Word List encoded from the HVLT-R
Timepoint [1] 376742 0
Time from study registration to the earliest evidence of clinical progression, radiographic progression or neurocognitive progression, assessed up to 16 years
Secondary outcome [2] 376743 0
Time to neurocognitive progression, assessed using the Hopkins Verbal Learning Test-Revised for Free Recall, Delayed Recall, and Delayed Recognition; the Controlled Oral Word Association test; and the Trail Making Test Part A or B - Estimated by Kaplan-Meier method and analyzed by Cox regression model adjusting all stratification factors. For each test in the battery, a standard error of measurement will be used to derive the Reliable Change Index (RCI) which will be used to represent the 90% confidence interval for the difference in raw scores from baseline to follow-up assessment will be coded as 1 (deterioration), 2 (no change), and 3 (improved) according to the RCI. This is a composite secondary outcome.
Timepoint [2] 376743 0
Time from study registration to the first cognitive failure, assessed up to 16 years
Secondary outcome [3] 376744 0
Overall survival - The Cox proportional hazards model will be used to assess whether the distributions of overall survival times differ with respect to treatment regimen having adjusted for all stratification factors (cooperative groups, age, and Performance Score). The distribution of overall survival for Arm A and B will be estimated using the Kaplan-Meier method. The hazard ratios and median survivals will be estimated with their 95% confidence intervals.
Timepoint [3] 376744 0
Time from study registration to time of death due to any cause, assessed up to 16 years
Secondary outcome [4] 376745 0
Objective tumor response defined as a complete response or partial response - Summarized for each arm and compared between the arms using the Chi square test.
Tumor response will be assessed at the treating site, using contrast and non-contrast brain magnetic resonance imaging (MRI) and based on the Response Assessment in Neuro Oncology, at scheduled intervals until progression of disease or lost to follow up. For patients who do not progress or die, Progression Free Survival will be censored at the time of initiation of alternative anticancer therapy, date of last radiologic assessment, or time of last contact (or whichever comes first).
Timepoint [4] 376745 0
Up to 16 years
Secondary outcome [5] 376746 0
Treatment-related adverse events according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. The maximum grade for each type of treatment related adverse event will be recorded for each patient, and frequency tables for each arm will be reviewed to determine patterns. In addition, will review all adverse event data that is graded as 3, 4, or 5 and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing. Adverse events and treatment related adverse events will be evaluated using all patients. Treatment related adverse events will be tabulated for each arm.
Patients are advised that possible risks, side effects and discomforts include the following:
Radiotherapy
- You may experience some, all, or none of the following side effects:
Very common side effects of radiotherapy (experienced by more than 1 in 10 patients)
- Fatigue (tiredness or lack of energy)
- Skin and hair - reddening or tanning of the skin; hair loss in the treatment area
- Symptoms related to the gut: nausea, vomiting
- Headache
Uncommon side effects of radiotherapy (experienced by between 1 in 100 and 1 in 1,000 patients)
- Damage to normal brain: specific effects depend upon the location of the area(s) of damage but may include a decrease in judgment, memory, emotions, vision, hearing, sensation, ability to control movement; or an increase in sleepiness (drowsiness), confusion, irritability
Procarbazine: You may experience some, all, or none of the following side effects:

Very common side-effects of procarbazine (experienced by more than 1 in 10 patients):
- Fatigue (tiredness or lack of energy)
- Symptoms related to the gut: nausea, vomiting, loss of appetite, dry mouth
- Decreased production of red cells, white cells, or platelets by the bone marrow
- Low white blood cell counts could put you at risk for infection
- Low red blood cell counts (anaemia) could make you feel tired
- Low platelet counts could put you at increased risk of bleeding

Common side-effects of procarbazine (experienced by between 1 in 10 and 1 in 100 patients):
- Hair thinning, although this is usually minor
- Allergic reaction which could include fever, chills, swelling of body, shortness of breath
- Skin changes: irritation, rash, flaking, itching, small broken blood vessels in skin or lining of mouth, darkening, hives, raised itchy areas, flushing, tingling, burning, or prickling sensation, yellowing of skin and/or eyes
- Loss of fertility (men and women - meaning, your ability to conceive or father a child may be affected) or development of irregular menstruation (periods) in women
- Low sperm count
- Abnormal liver function
- Inflammation of the lungs
- Secondary leukemia and/or myelodysplastic syndrome (damage to the bone marrow that affects normal blood cell production) may develop years later as a result of this treatment

Uncommon side-effects of procarbazine (experienced by between 1 in 100 and 1 in 1,000 patients):
- Headache
- Loss of muscle coordination including awkward, unsteady walking
- Nerve damage, possible numbness, pain, and/or loss of strength

Lomustine (CCNU): You may experience some, all, or none of the following side effects:

Very common side-effects of lomustine (CCNU) (experienced by more than 1 in 10 patients):
- Symptoms related to the gut: nausea, vomiting
- Decreased production of white cells or platelets by the bone marrow:
- Low white blood cell counts could put you at risk for infection
- Low platelet counts could put you at increased risk of bleeding

Common side-effects of lomustine (CCNU) (experienced by between 1 in 10 and 1 in 100 patients):
- Low red blood cell counts (anaemia) could make you feel tired
- Symptoms related to the gut: loss of appetite, diarrhoea
- High level of liver enzymes in the blood
- Mouth sores
- Loss of fertility (meaning, your ability to conceive or father a child may be affected)
- Hair loss

Uncommon side-effects of lomustine (CCNU) (experienced by between 1 in 100 and 1 in 1,000 patients):
- Drowsiness
- Difficulty walking
- Lung damage causing shortness of breath and dry cough
- Kidney damage
- Secondary leukemia and/or myelodysplastic syndrome (damage to the bone marrow that affects normal blood cell production) may develop years later as a result of this treatment
- Speech disorders: stuttering, slurry and slow speech

Vincristine: You may experience some, all, or none of the following side effects:

Very common side-effects of vincristine (experienced by more than 1 in 10 patients):
- Thinning of body and head hair
- Rash

Common side-effects of vincristine (experienced by between 1 in 10 and 1 in 100 patients):
- Blood pressure change when rising from a seated position
- High blood pressure or low blood pressure
- Confusion
- Loss of voluntary muscle movement in the face due to nerve damage
- Fever
- Headache
- Difficulty falling and/or staying asleep
- Irregular muscle movements
- Increased uric acid in the blood which may cause inflammation of the joints (also called ‘gout’)
- Swelling due to fluid or water
- Symptoms related to the gut: abdominal pain/cramps, nausea, vomiting, diarrhea, constipation, decreased appetite
- Mouth - metallic taste, jaw pain
- Weight loss
- Difficulties with urination - muscular weakness in the bladder, painful or difficult urination (dysuria), excessive urination, inability to urinate
- Decreased production of white cells or platelets by the bone marrow:
- Low white blood cell counts could put you at risk for infection
- Low platelet counts could put you at increased risk of bleeding
- Skin blistering at the injection site
- Inflammation of the veins at the injection site
- Skin irritation and ulceration if the drug leaks to tissue surrounding the injection site
- Cramping
- Pain - leg pain, muscle pain, throat pain, salivary gland pain
- Weakness
- Inflammation of the nerves, usually in the hands and feet, (also called neuopathy) which could be associated with numbness, tingling, pain, burning or prickling of the fingers and toes. If severe, this can lead to weakness in feet and arms
- Loss of deep tendon reflexes e.g. knee reflex
- Reduced reproduction and fertility (meaning, your ability to conceive or father a child may be affected)
- Amenorrhoea: stopping of menstruation (periods)

Uncommon side-effects of vincristine (experienced by between 1 in 100 and 1 in 1,000 patients):
- Low blood sodium and concentrated urine
- Mouth sores
- Ruptured bowel (symptoms include severe abdominal pain and tenderness)
- Involuntary changes in body movement, function, sensation, awareness or behavior (seizure)
- Eye problems - wasting away of the nerves and structures of the eye, inability to tolerate light, rapid jerky movements of the eye
- Ear problems - difficulties with balance, dizziness, temporary or permanent partial or complete loss of hearing.
- Drowsiness
- Allergic reactions with rash and swelling

Temozolomide given at the same time as radiotherapy - You may experience some, all, or none of the following side effects:

Very common side-effects of temozolomide plus radiotherapy (experienced by more than 1 in 10 patients):
- Headache
- Symptoms related to the gut: nausea, vomiting, constipation, loss of appetite
- Rash
- Hair thinning
- Tiredness

Common side-effects of temozolomide plus radiotherapy (experienced by between 1 in 10 and 1 in 100 patients):
- Mouth infections
- Wound infection
- Decreased production of white cells or platelets by the bone marrow:
- Low white blood cell counts could put you at risk for infection
- Low platelet counts could put you at increased risk of bleeding
- Increased sugar in the blood
- Weight loss
- Change in mental state or alertness, anxiety/depression, confusion, forgetfulness, difficulty concentrating
- Mood swings
- Symptoms related to movement or activities: difficulty speaking, impaired balance, dizziness, shaking
- Sleep - sleepiness, inability to fall asleep or stay asleep
- Eyes - abnormal or blurry vision, double vision
- Hearing impairment
- Shortness of breath
- Cough
- Water retention which can cause swelling in the face, hands, feet or legs
- Heartburn
- Mouth - abnormal taste, difficulty swallowing, dry mouth
- Skin - skin irritation or redness, dry skin, itching, tingling sensation, bruising
- Muscles and joints - muscle weakness, painful joints, muscle aches and pains
- Urination - frequent urination, difficulty in holding your urine
- Allergic reaction
- Fever
- Radiation injury – scalp irritation, hair loss, impaired memory and cognition
- Abnormal liver function tests

Uncommon side-effects of temozolomide plus radiotherapy (experienced by between 1 in 100 and 1 in 1,000 patients):
- Low potassium level in the blood, which may cause muscle weakness or an abnormal heart rhythm
- Weight gain
- Hallucination and memory impairment
- Partial paralysis – reduced muscle strength in face, arms or legs
- Impaired coordination
- Impaired sensation
- Eyes - partial loss of vision, dry or painful eyes
- Ears - deafness, infection of the middle ear, ringing in the ears, earache
- Palpitations (when you can feel your heart beat)
- High blood pressure
- Pneumonia
- Inflammation of your sinuses
- Bronchitis
- Cold symptoms - runny nose, watery eyes, cough
- Difficulty controlling your bowel movements
- Skin - peeling skin, increased sensitivity to sunlight, change in skin colour, red spots under the skin, increased sweating
- Muscle damage
- Back pain
- Sexual impotence
- Hot flushes and/or shivering
- Mouth - discolouration of your tongue, thirst, tooth decay
- Change in your sense of smell

Temozolomide alone - You may experience some, all, or none of the following side effects:

Very common side-effects of temozolomide alone (experienced by more than 1 in 10 patients):
- Headache
- Symptoms related to the gut: nausea, vomiting, constipation, decreased appetite
- Tiredness
- Hair loss

Common side-effects of temozolomide alone (experienced by between 1 in 10 and 1 in 100 patients):
- Decreased production of white cells or platelets by the bone marrow:
- Low white blood cell counts could put you at risk for infection
- Low platelet counts could put you at increased risk of bleeding
- Weight loss
- Dizziness and/or weakness
- Shortness of breath
- Cough
- Symptoms related to the gut: abdominal pain, diarrhoea
- Skin - itching, tingling sensation
- Allergic reaction which may cause rash, low blood pressure, wheezing, shortness of breath, swelling of the face or throat
- Fever and/or shivering
- Change in taste

Uncommon side-effects of temozolomide alone (experienced by between 1 in 100 and 1 in 1,000 patients):
- Skin – redness, hives, skin eruption
- Liver damage which may cause yellowing of eyes and skin, swelling and may result in liver failure
- Herpes infection of the brain (known as encephalitis) and its membranes due to low blood counts
- Severely reduced number of blood cells
- Infections including pneumonia
Imaging:

There are no known effects from exposure to the magnetic fields. There is no radiation associated with an MRI scan which is the standard scanning method for this study. However, if you have a metal device (such as a pacemaker), are not comfortable with close spaces or are unable to lie still comfortably, you may not be able to have an MRI and must have a CT scan instead. Please tell your doctor if you have a pacemaker or any metal plates or clips in your body.

Most MRI scanners make loud knocking noises during use; you will be asked to wear earplugs to minimise any discomfort from noise.

If you have CT scans or an X-ray, you will be exposed to a small amount of radiation. The amount of radiation you will receive has a very low risk of harmful effects.

You may feel claustrophobic or anxious inside the MRI scanner. You may experience some discomfort and fatigue from lying in a confined space within the scanner.

Other side-effects:

- Side-effects associated with blood draws or use of an IV catheter may include infection, bruising, redness, discomfort, or bleeding at the needle puncture site
- Answering study questions and completing study questionnaires (including computer-based tests) may make you feel tired

Child-bearing
Chemotherapy may cause temporary or permanent sterility (i.e. inability to conceive or father a child). Please discuss this with your study doctor if you have any concerns about future fertility.
The drugs in this study can affect the unborn child. Because of this, it is important that study participants are not pregnant or breast-feeding and do not become pregnant during the course of the study. You must not take part in the study if you are pregnant or trying to become pregnant, or are breast-feeding. If you are a woman and child-bearing is a possibility, you will be required to undergo a pregnancy test prior to starting the study. If you are a man, you should not father a child or donate sperm for at least 6 months after the last dose of study medication.
Both men and women are strongly advised to use effective contraception during the course of the study and for a period of 6 months after completion of the study medication. You should discuss methods of effective contraception with your study doctor.
Timepoint [5] 376746 0
Up to 16 years

Eligibility
Key inclusion criteria
Pre-Registration
* This review is mandatory prior to registration to confirm eligibility; patients must
be willing to submit tissue samples for mandatory central pathology review submission; it should be initiated as soon after surgery as possible

- Tissue must have been determined to have local 1p/9q co-deletion and IDH mutation prior to submission for central path review

- Tumor tissue must show co-deletion of chromosomes 1p and 19q; for eligibility,
the 1p/19q analysis results will be accepted from the local site, as determined
by either a locally available or reference laboratory; acceptable methods for
determination of 1p/19q loss include fluorescent in-situ hybridization (FISH), by
genomic sequencing or methylomic analyses;

- Tumor must also show evidence of IDH mutation by immunohistochemistry or genomic
analyses; this should be performed at the local site

Registration

- Newly diagnosed and =< 3 months from surgical diagnosis; patients are also eligible if they have had a prior surgical procedure > 3 months earlier for low grade glioma, as
long as the patient has not received prior radiation or prior chemotherapy

- Histological evidence of World Health Organization (WHO) grade III anaplastic glioma
or WHO grade II low grade glioma with locally diagnosed combined 1p/19q loss and the presence of an either IDH1 or IDH2, both as established by a local or referenced
laboratory qualified for the study

* Note: mixed gliomas are eligible, regardless of the degree of astrocytic or
oligodendrocytic predominance, as long as the tumor is also co-deleted for 1p and 19q

- Patients with codeleted low grade gliomas must also be considered "high risk" by
exhibiting one or more of the following characteristics:

- Age >= 40 and any surgical therapy

- Age < 40 with prior and subtotal resection or biopsy (i.e., anything less than
gross total resection)

- Documented growth following prior surgery (NOTE: patients with prior surgery
cannot have received prior radiation, chemotherapy or targeted therapy)

- Intractable seizures

- Surgery (partial or gross total resection or biopsy) must be performed >= 2 weeks
prior to registration; patient must have recovered adequately from the effects of
surgery

- Absolute neutrophil count (ANC) >= 1,500/mm^3 obtained =< 21 days prior to
registration

- Platelet (PLTs) count >= 100,000/mm^3 obtained =< 21 days prior to registration

- Hemoglobin (Hgb) > 9.0 g/dL obtained =< 21 days prior to registration

- Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) obtained =< 21 days
prior to registration

- Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 3
x ULN obtained =< 21 days prior to registration

- Creatinine =< 1.5 x ULN obtained =< 21 days prior to registration

- Negative serum or urine pregnancy test done =< 7 days prior to registration, for women
of childbearing potential only

- Willingness and ability to personally complete neurocognitive testing (without
assistance) and willingness to complete the QOL testing, (either personally or with
assistance)

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1 or 2

- Written informed consent

- Willingness to return to enrolling institution for follow-up during the active
monitoring phase (that is, the active treatment and observation portion) of the
study); patients who have been formally transferred to another active and approved
site participating in this study would not need to return to the enrolling institution
for this purpose

- Willingness to allow the provision of tissue samples for correlative research, as long
as adequate tissues are available; patients will not be excluded from participation in
the study, if they are willing to allow provision of tissues for the correlative
research, but there are insufficient quantities of tissue for the correlative analyses
(e.g., a patient otherwise eligible and willing who had biopsy only) Willingness to
allow the provision of blood samples for correlative research; patients are not
excluded from participation in the study, if they are willing to provide the mandatory
biospecimens for translational/correlative research, but for logistical reasons the
specimens(s) were not obtainable or if the volume collected was insufficient

Registration
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- The following categories are ineligible:

- Pregnant women

- Nursing women

- Men or women of childbearing potential who are unwilling to employ adequate
contraception or contraceptive method during this study and 6 months following
the completion of chemotherapy treatments

- History of prior radiation therapy or chemotherapy for glioma; note: patients who have
a history of prior low grade glioma (with or without a distant history of prior
surgery for that glioma), but who have never received prior chemotherapy or radiation
therapy for the glioma are eligible for the study

- Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment
of the investigator, would make the patient inappropriate for entry into this study or
interfere significantly with the proper assessment of safety and toxicity of the
prescribed regimens

- Concomitant serious immunocompromised status (other than that related to concomitant
steroids) that would compromise the safety of the patient on the study

- Patients known to be human immunodeficiency virus (HIV) positive and currently
receiving retroviral therapy are not eligible; note: patients known to be HIV
positive, but without clinical evidence of an immunocompromised state, are eligible
for the study

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- Receiving any other investigational agent that would be considered as a treatment for
the primary neoplasm

- Other active malignancy within 5 years of registration; exceptions: non-melanotic skin
cancer or carcinoma-in-situ of the cervix; note: if there is a history of prior
malignancy, the patient is not eligible if they are receiving other specific treatment
(with the exclusion of hormonal therapy or Her-2 inhibitors) for their cancer or if
they have received prior total body irradiation which included the brain

- History of myocardial infarction =< 6 months, or congestive heart failure requiring
use of ongoing maintenance therapy for life-threatening ventricular arrhythmias

- Recent history of hepatitis infection or if the treating physician determined that the
patient would be at significant risk of reactivation of hepatitis

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
Contractual reasons with the international group.
Date of first participant enrolment
Anticipated
1/10/2022
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
360
Accrual to date
Final
Recruitment outside Australia
Country [1] 22042 0
United States of America
State/province [1] 22042 0
Alabama
Country [2] 22043 0
United States of America
State/province [2] 22043 0
Alaska
Country [3] 22044 0
United States of America
State/province [3] 22044 0
Arizona
Country [4] 22045 0
United States of America
State/province [4] 22045 0
California
Country [5] 22046 0
United States of America
State/province [5] 22046 0
Colorado
Country [6] 22047 0
United States of America
State/province [6] 22047 0
Connecticut
Country [7] 22048 0
United States of America
State/province [7] 22048 0
District of Columbia
Country [8] 22049 0
United States of America
State/province [8] 22049 0
Florida
Country [9] 22050 0
United States of America
State/province [9] 22050 0
Georgia
Country [10] 22051 0
United States of America
State/province [10] 22051 0
Idaho
Country [11] 22052 0
United States of America
State/province [11] 22052 0
Illinois
Country [12] 22053 0
United States of America
State/province [12] 22053 0
Indiana
Country [13] 22054 0
United States of America
State/province [13] 22054 0
Iowa
Country [14] 22055 0
United States of America
State/province [14] 22055 0
Kentucky
Country [15] 22056 0
United States of America
State/province [15] 22056 0
Louisiana
Country [16] 22057 0
United States of America
State/province [16] 22057 0
Maine
Country [17] 22058 0
United States of America
State/province [17] 22058 0
Maryland
Country [18] 22059 0
United States of America
State/province [18] 22059 0
Massachusetts
Country [19] 22060 0
United States of America
State/province [19] 22060 0
Michigan
Country [20] 22061 0
United States of America
State/province [20] 22061 0
Minnesota
Country [21] 22062 0
United States of America
State/province [21] 22062 0
Missouri
Country [22] 22063 0
United States of America
State/province [22] 22063 0
Montana
Country [23] 22064 0
United States of America
State/province [23] 22064 0
Nebraska
Country [24] 22065 0
United States of America
State/province [24] 22065 0
Nevada
Country [25] 22066 0
United States of America
State/province [25] 22066 0
New Hampshire
Country [26] 22067 0
United States of America
State/province [26] 22067 0
New Jersey
Country [27] 22068 0
United States of America
State/province [27] 22068 0
New Mexico
Country [28] 22069 0
United States of America
State/province [28] 22069 0
New York
Country [29] 22070 0
United States of America
State/province [29] 22070 0
North Carolina
Country [30] 22071 0
United States of America
State/province [30] 22071 0
North Dakota
Country [31] 22072 0
United States of America
State/province [31] 22072 0
Ohio
Country [32] 22073 0
United States of America
State/province [32] 22073 0
Oklahoma
Country [33] 22074 0
United States of America
State/province [33] 22074 0
Oregon
Country [34] 22075 0
United States of America
State/province [34] 22075 0
Pennsylvania
Country [35] 22076 0
United States of America
State/province [35] 22076 0
South Carolina
Country [36] 22077 0
United States of America
State/province [36] 22077 0
South Dakota
Country [37] 22078 0
United States of America
State/province [37] 22078 0
Tennessee
Country [38] 22079 0
United States of America
State/province [38] 22079 0
Texas
Country [39] 22080 0
United States of America
State/province [39] 22080 0
Utah
Country [40] 22081 0
United States of America
State/province [40] 22081 0
Virginia
Country [41] 22082 0
United States of America
State/province [41] 22082 0
Washington
Country [42] 22083 0
United States of America
State/province [42] 22083 0
West Virginia
Country [43] 22084 0
United States of America
State/province [43] 22084 0
Wisconsin
Country [44] 22085 0
Austria
State/province [44] 22085 0
Vienna
Country [45] 22086 0
Belgium
State/province [45] 22086 0
Antwerpen
Country [46] 22087 0
Canada
State/province [46] 22087 0
Alberta
Country [47] 22088 0
Canada
State/province [47] 22088 0
British Columbia
Country [48] 22089 0
Canada
State/province [48] 22089 0
Manitoba
Country [49] 22090 0
Canada
State/province [49] 22090 0
Ontario
Country [50] 22091 0
Canada
State/province [50] 22091 0
Quebec
Country [51] 22092 0
Canada
State/province [51] 22092 0
Saskatchewan
Country [52] 22093 0
France
State/province [52] 22093 0
Lyon
Country [53] 22094 0
France
State/province [53] 22094 0
Nice
Country [54] 22095 0
France
State/province [54] 22095 0
Villejuif
Country [55] 22096 0
Netherlands
State/province [55] 22096 0
Amsterdam
Country [56] 22097 0
Netherlands
State/province [56] 22097 0
Groningen
Country [57] 22098 0
Netherlands
State/province [57] 22098 0
Maastricht
Country [58] 22099 0
Netherlands
State/province [58] 22099 0
Rotterdam
Country [59] 22100 0
Switzerland
State/province [59] 22100 0
Zurich

Funding & Sponsors
Funding source category [1] 304246 0
Government body
Name [1] 304246 0
Cancer Australia
Country [1] 304246 0
Australia
Funding source category [2] 304574 0
Government body
Name [2] 304574 0
Cancer Council NSW
Country [2] 304574 0
Australia
Primary sponsor type
Other
Name
Alliance for Clinical Trials in Oncology
Address
221 Longwood Avenue,
Boston, MA 02115
Country
United States of America
Secondary sponsor category [1] 312714 0
None
Name [1] 312714 0
Address [1] 312714 0
EORTC has decided not to participate in the study.
Country [1] 312714 0
Other collaborator category [1] 281025 0
Government body
Name [1] 281025 0
National Cancer Institute (NCI)
Address [1] 281025 0
31 Center Drive
Building 31, Bethesda, Maryland, 20814, USA
Country [1] 281025 0
United States of America
Other collaborator category [2] 281027 0
Other Collaborative groups
Name [2] 281027 0
Canadian Cancer Trials Group
Address [2] 281027 0
Queen's University
10 Stuart Street
Kingston, Ontario, K7L 3N6
Country [2] 281027 0
United States of America

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304704 0
SLHD Human Research Ethics Committee (RPA)
Ethics committee address [1] 304704 0
Research Ethics and Governance Office (REGO)
Royal Prince Alfred Hospital
Missenden Road
CAMPERDOWN NSW 2050
Ethics committee country [1] 304704 0
Australia
Date submitted for ethics approval [1] 304704 0
19/08/2019
Approval date [1] 304704 0
11/09/2019
Ethics approval number [1] 304704 0

Summary
Brief summary
The aim of this study is to evaluate whether giving radiation with concomitant and adjuvant temozolomide versus radiation with adjuvant PCV is more effective in treating anaplastic glioma or low grade glioma.

Who is it for?

You may eligible for this study if you are 18 years or older and newly diagnosed with Glioma with tumor tissue determined to have local 1p/9q co-deletion and yet to receive radiation or chemotherapy

Study details

Participants will be randomly allocated (50/50 chance) to either ARM A or ARM B.
1.Participants in Arm A will undergo radiotherapy on days 1-5 for 5-7 weeks. Patients also receive procarbazine hydrochloride orally on days 8-21, lomustine orally on day 1 and vincristine sulfate intravenously on days 8 and 29 of courses 3-8. Treatment repeats every 6-7 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
2.Participants allocated to Arm B will undergo radiotherapy and receive temozolomide orally once daily on days 1-5 for 5-7 weeks. Beginning 4 weeks after completion of concurrent chemoradiotherapy, patients receive adjuvant temozolomide once daily on days 1-5. Treatment with adjuvant temozolomide repeats every 4 weeks for 6-12 courses in the absence of disease progression and unacceptable toxicity.

Involvement in the study may include blood tests, urine tests, medical imaging scans, quality of life questionnaires, pregnancy test, neurocognitive exam and completion of medication diary.

It is hoped this study can provide greater insight into the most effective treatment combination for patients with Glioma
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 97934 0
Dr Elizabeth Hovey
Address 97934 0
NHMRC Clinical Trials Centre
The University of Sydney
Lifehouse Level 6
119- 143 Missenden Road
Camperdown NSW 2050
Country 97934 0
Australia
Phone 97934 0
+61 02 9562 5000
Fax 97934 0
Email 97934 0
[email protected]
Contact person for public queries
Name 97935 0
CODEL Trial Operations Coordinator
Address 97935 0
NHMRC Clinical Trials Centre
The University of Sydney
Lifehouse Level 6
119- 143 Missenden Road
Camperdown NSW 2050
Country 97935 0
Australia
Phone 97935 0
+61 02 9562 5000
Fax 97935 0
Email 97935 0
[email protected]
Contact person for scientific queries
Name 97936 0
CODEL Trial Operations Coordinator
Address 97936 0
NHMRC Clinical Trials Centre
The University of Sydney
Lifehouse Level 6
119- 143 Missenden Road
Camperdown NSW 2050
Country 97936 0
Australia
Phone 97936 0
+61 02 9562 5000
Fax 97936 0
Email 97936 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
This has not been discussed as to what will be available for this trial.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.