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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02358356




Registration number
NCT02358356
Ethics application status
Date submitted
4/11/2014
Date registered
9/02/2015
Date last updated
5/07/2022

Titles & IDs
Public title
Capecitabine ON Temozolomide Radionuclide Therapy Octreotate Lutetium-177 NeuroEndocrine Tumours Study
Scientific title
Capecitabine ON Temozolomide Radionuclide Therapy Octreotate Lutetium-177 NeuroEndocrine Tumours Study
Secondary ID [1] 0 0
CTC0120 / AG0114NET
Universal Trial Number (UTN)
Trial acronym
CONTROL NETS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Midgut Neuroendocrine Tumours 0 0
Pancreatic Neuroendocrine Tumours 0 0
Condition category
Condition code
Cancer 0 0 0 0
Neuroendocrine tumour (NET)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - octreotate
Treatment: Drugs - Capecitabine
Treatment: Drugs - Temozolomide

Active comparator: PRRT - 7.8GBq 177Lu Octreotate (Lutate) given intravenously (IV) on day 1 every 8 weeks for 4 cycles.

Active comparator: CAPTEM - Oral capecitabine 750mg/m2 b.i.d. days 1-14 and temozolomide 75mg/m2 b.i.d. days 10-14 every 28 day cycle, up to 8 cycles.

Experimental: PRRT/CAPTEM - 7.8GBq 177Lu Octreotate (Lutate) given intravenously (IV) on day 10 every 8 weeks for 4 cycles, with concurrent oral capecitabine 750mg/m2 b.i.d. days 1-14 and temozolomide 75mg/m2 b.i.d. days 10-14 up to 4 cycles.


Treatment: Drugs: octreotate
7.8GBq 177Lu Octreotate (Lutate) given intravenously (IV)

Treatment: Drugs: Capecitabine
oral capecitabine 750mg/m2 b.i.d.

Treatment: Drugs: Temozolomide
temozolomide 75mg/m2 b.i.d.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival
Timepoint [1] 0 0
12 months for pNETs and 24 months for mNets
Secondary outcome [1] 0 0
Objective tumour response rate (partial or complete response) as per RECIST v1.1 criteria
Timepoint [1] 0 0
12 months or 24 months as appropriate
Secondary outcome [2] 0 0
Overall survival (death from any cause)
Timepoint [2] 0 0
12 months or 24 months as appropriate
Secondary outcome [3] 0 0
Safety (rates of adverse events worst grade according to NCI CTCAE v4.0)
Timepoint [3] 0 0
12 months or 24 months as appropriate
Secondary outcome [4] 0 0
Quality of life (QOL scores determined at beginning, during treatment and until disease progression)
Timepoint [4] 0 0
12 months or 24 months as appropriate
Secondary outcome [5] 0 0
Resource utilisation (use of healthcare resources) and cost-effectiveness (Health utility score determined at beginning, during treatment and until end of follow up, correlated with MBS & PBS data)
Timepoint [5] 0 0
12 months or 24 months as appropriate
Secondary outcome [6] 0 0
Clinical Benefit
Timepoint [6] 0 0
12 months or 24 months as appropriate

Eligibility
Key inclusion criteria
* Adults =18 years old with histologically proven, moderate to well-differentiated G1/2 pancreatic or midgut NETs with Ki-67 < 20%;
* The presence of somatostatin receptor avidity suitable for PRRT demonstrated on 68Ga-octreotate PET scan;
* Progressive advanced/metastatic disease that has progressed during or after = 2 prior systemic therapies;
* Unresectable disease, determined by an appropriately specialized surgeon or deemed not suitable for liver directed therapies where liver is the only site of disease;
* ECOG performance status 0-2;
* Ability to swallow oral medication;
* Adequate renal function (measured creatinine clearance > 50 ml/min by DTPA or 51CR-EDTA), bone marrow function (Hb > 9 g/d/L, ANC > 1.5 x109L, and platelets > 100 x 10/L);
* Adequate liver function (serum total bilirubin = 1.5 x ULN, and Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP) = 2.5 x ULN (= 5 x ULN for patients with liver metastases)). INR = 1.5 (or on a stable dose of LMW heparin for >2 weeks at time of enrolment .);
* Life expectancy of at least 9 months;
* Study treatment both planned and able to start within 28 days of randomisation; )
* Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments;
* Signed, written informed consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Primary NETs other than small bowel (midgut) or pancreatic NETs;
* Cytotoxic chemotherapy, targeted therapy, or biotherapy within the last four weeks;
* Prior intrahepatic 90Y microspheres, such as SIR-Spheres in the past six months;
* Prior Peptide Receptor Radionuclide Therapy;
* Major surgery/surgical therapy for any cause within one month;
* Surgical therapy of loco-regional metastases within the last three months prior to randomisation;
* Uncontrolled metastatic disease to the central nervous system. To be eligible, CNS metastases should have been treated with surgery and/or radiotherapy and the patient should have been receiving a stable dose of steroids for at least 2 weeks prior to randomisation, with no deterioration in neurological symptoms during this time;
* Poorly controlled concurrent medical illness. E.g. unstable diabetes (Note: optimal glycaemic control should be achieved before starting trial therapy); Symptomatic NYHA class III or IV congestive cardiac failure, myocardial infarction within 6 months of start of the study, serious uncontrolled cardiac arrhythmia, unstable angina, or any other clinically significant cardiac disease;
* History of other malignancies within 5 years except where treated with curative intent AND with no current evidence of disease AND considered not to be at risk of future recurrence Patients with a past history of adequately treated carcinoma-in-situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or superficial transitional cell carcinoma of the bladder are eligible;
* Any uncontrolled known active infection, including chronic active hepatitis B, hepatitis C, or HIV. Testing for these is not mandatory unless clinically indicated. Participants with known Hepatitis B/C infection will be allowed to participate providing evidence of viral suppression has been documented and the patient remains on appropriate anti-viral therapy;
* Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of capecitabine/temozolomide (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or substantial small bowel resection);
* Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule, including alcohol dependence or drug abuse;
* Pregnancy, lactation, or inadequate contraception. Women must be post-menopausal, infertile, or use a reliable means of contraception. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to registration. Men must have been surgically sterilised or use a (double if required) barrier method of contraception .

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 2
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
1/11/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
31/10/2021
Sample size
Target
Accrual to date
Final
75
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [2] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [3] 0 0
Peter MacCallum Cancer Centre - East Melbourne
Recruitment hospital [4] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 0 0
2065 - St Leonards
Recruitment postcode(s) [2] 0 0
4029 - Herston
Recruitment postcode(s) [3] 0 0
8006 - East Melbourne
Recruitment postcode(s) [4] 0 0
6150 - Murdoch

Funding & Sponsors
Primary sponsor type
Other
Name
Australasian Gastro-Intestinal Trials Group
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Two parallel phase II randomized open label trials of Lutetium-177 Octreotate (177Lu-Octreotate) peptide receptor radionuclide therapy (PRRT) and capecitabine (CAP)/temozolomide (TEM) chemotherapy (chemo): (i) versus CAPTEM alone in the treatment of low to intermediate grade pancreatic neuroendocrine tumours (pNETs); (ii) versus PRRT alone in the treatment of low to intermediate grade mid gut neuroendocrine tumours (mNETs).
Trial website
https://clinicaltrials.gov/study/NCT02358356
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Nick Pavlakis, Associate Professor
Address 0 0
Royal North Shore Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02358356