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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01480479




Registration number
NCT01480479
Ethics application status
Date submitted
21/11/2011
Date registered
29/11/2011
Date last updated
16/01/2018

Titles & IDs
Public title
Phase III Study of Rindopepimut/GM-CSF in Patients With Newly Diagnosed Glioblastoma
Scientific title
An International, Randomized, Double-Blind, Controlled Study of Rindopepimut/GM-CSF With Adjuvant Temozolomide in Patients With Newly Diagnosed, Surgically Resected, EGFRvIII-positive Glioblastoma
Secondary ID [1] 0 0
CDX110-04
Universal Trial Number (UTN)
Trial acronym
ACT IV
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Glioblastoma 0 0
Small Cell Glioblastoma 0 0
Giant Cell Glioblastoma 0 0
Gliosarcoma 0 0
Glioblastoma With Oligodendroglial Component 0 0
Condition category
Condition code
Cancer 0 0 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Rindopepimut (CDX-110) with GM-CSF
Treatment: Drugs - Temozolomide
Treatment: Drugs - KLH

Experimental: Rindopepimut/GM-CSF plus Temozolomide -

Active comparator: KLH plus Temozolomide -


Treatment: Drugs: Rindopepimut (CDX-110) with GM-CSF
Two intradermal injections two weeks apart, followed by monthly injections until tumor progression or intolerance.

Each dose will be 0.8 mL containing approximately 500 mcg CDX-110 and 150 mcg GM CSF.

Treatment: Drugs: Temozolomide
150 to 200 mg/m2 for 5 days during each 28-day cycle for a minimum of six cycles or a maximum of 12 cycles, or until intolerance or progression.

Treatment: Drugs: KLH
Two intradermal injections two weeks apart, followed by monthly injections until tumor progression or intolerance. Each dose will be 0.8mL containing approximately 100mcg of KLH.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival
Timepoint [1] 0 0
During treatment and every three months from end of treatment through end of study or approximately up to 5 years.
Secondary outcome [1] 0 0
Progression-free survival
Timepoint [1] 0 0
Every 12 weeks from Day 1 through progression or initiation of other anti-cancer therapy
Secondary outcome [2] 0 0
Safety and Tolerability
Timepoint [2] 0 0
Until day 28 of follow up

Eligibility
Key inclusion criteria
Inclusion Criteria-

Among other criteria, patients must meet the following conditions to be eligible for the study:

1. Adult patients, = 18 years old
2. Newly diagnosed glioblastoma
3. Attempted surgical resection followed by conventional chemoradiation
4. Documented EGFRvIII positive tumor status by a Sponsor designated laboratory
5. No evidence of progressive disease from the post-operative period to the post-chemoradiation period
6. Candidate for, and agrees to receive, adjuvant (maintenance) temozolomide therapy
7. Systemic corticosteroid therapy at =2 mg of dexamethasone or equivalent per day for at least 3 days prior to randomization
8. WHO-ECOG Performance Status = 2
9. Patients of childbearing/reproductive potential will be instructed to use birth control as defined by your doctor.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria-

Among other criteria, patients who meet the following conditions are NOT eligible for the study:

1. Stereotactic biopsy only (without further surgical resection)
2. Presence of diffuse leptomeningeal disease, gliomatosis cerebri, or infratentorial disease.
3. History, presence, or suspicion of metastatic disease
4. Patients who have received any additional treatment for glioblastoma, aside from surgical resection and chemoradiation with temozolomide
5. Active systemic infection requiring treatment
6. History of any malignancy (other than glioblastoma) during the last three years except non-melanoma skin cancer, in situ cervical cancer, treated superficial bladder cancer, cured, early-stage prostate cancer in a patient with PSA level less than ULN,or other carcinoma in situ that has been adequately treated and cured.
7. Planned major surgery
8. Evidence of current drug or alcohol abuse
9. Known allergy or hypersensitivity to keyhole limpet hemocyanin (KLH), GM-CSF (sargramostim; LEUKINE®), polysorbate 80 or yeast derived products, or a history of anaphylactic reactions to shellfish proteins
10. Severe acute or chronic medical or psychiatric condition or laboratory abnormality that could increase the risk associated with participating in a clinical trial
11. Women who are pregnant or lactating

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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/11/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/11/2016
Sample size
Target
Accrual to date
Final
745
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,VIC,WA
Recruitment hospital [1] 0 0
Prince of Wales Hospital - Randwick
Recruitment hospital [2] 0 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [3] 0 0
The Crown Princess Mary Cancer Centre, Westmead Hospital - Westmead
Recruitment hospital [4] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [5] 0 0
Mater Adult Hospital, Mater Misericordiae Health Services Brisbane Limited - South Brisbane
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Royal Adelaide Hospital - Adelaide
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Calvary North Adelaide Hospital - North Adelaide
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Royal Hobart Hospital - Hobart
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Launceston General Hospital - Launceston
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Monash Medical Centre - Clayton
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Austin Health - Heidelberg
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Epworth Healthcare - Richmond
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Sir Charles Gairdner Hospital - Nedlands
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Liverpool Hospital - Liverpool
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2031 - Randwick
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2605 - St Leonards
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2145 - Westmead
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4029 - Herston
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4101 - South Brisbane
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5000 - Adelaide
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5006 - North Adelaide
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7000 - Hobart
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7250 - Launceston
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3199 - Clayton
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3084 - Heidelberg
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3121 - Richmond
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06008 - Nedlands
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2107 - Liverpool
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Celldex Therapeutics
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This 2-arm, randomized, phase III study will investigate the efficacy and safety of the addition of rindopepimut (an experimental cancer vaccine that may act to promote anti-cancer effects in patients who have tumors that express the EGFRvIII protein) to the current standard of care (temozolomide) in patients with recently diagnosed glioblastoma, a type of brain cancer.

All patients will be administered temozolomide, the standard treatment for glioblastoma. Half the patients will be randomly assigned to receive rindopepimut and half the patients will be randomly assigned to receive a control called keyhole limpet hemocyanin.

Patients will be treated in a blinded fashion (neither the patient or the doctor will know which arm of the study the patient is on). Patients will be treated until disease progression or intolerance to therapy and all patients will be followed for survival.
Trial website
https://clinicaltrials.gov/study/NCT01480479
Trial related presentations / publications
Weller M, Butowski N, Tran DD, Recht LD, Lim M, Hirte H, Ashby L, Mechtler L, Goldlust SA, Iwamoto F, Drappatz J, O'Rourke DM, Wong M, Hamilton MG, Finocchiaro G, Perry J, Wick W, Green J, He Y, Turner CD, Yellin MJ, Keler T, Davis TA, Stupp R, Sampson JH; ACT IV trial investigators. Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV): a randomised, double-blind, international phase 3 trial. Lancet Oncol. 2017 Oct;18(10):1373-1385. doi: 10.1016/S1470-2045(17)30517-X. Epub 2017 Aug 23.
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
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Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01480479