None listed
Conditions
Brief summary
The CONTROL NETS study aims to determine the activity of capecitabine + temozolomide (CAPTEM)/peptide receptor radionuclide therapy (PRRT), alone and in combination, in both pancreatic neuroendocrine tumours (pNETS) and mid-gut neuroendocrine tumours (mNETS) patients. Who is it for? Participants must be at least 18 years of age, with advanced, non-operable mNETS or pNETS who have received 2 or fewer lines of treatment for their disease. Study details The study involves randomly allocating (by chance) participants to receive treatment. pNETS patients will receive either CAPTEM alone, or the experimental combination of CAPTEM/PRRT, whilst mNETS patients will receive either PRRT alone or CAPTEM/PRRT. Participants have a 2 in 3 chance of being allocated to the PRRT/CAPTEM treatment arm. Treatment on each arm continues for 32 weeks, followed by 12 months of follow-up (pNETS), and 24 months (mNETS). CAPTEM is chemotherapy (Capecitabine and Temozolomide) taken as tablets. PRRT is an injection of a radioactive compound called Lutate which is given into a vein on 4 occasions during treatment. Study participants will be asked to come to the clinic for study visits between 9 to 12 occasions during the treatment stage, depending on which treatment they receive. The visits will vary in length between 2 and 6 hours. CONTROL NETS will look at rates of progression free survival, overall survival, adverse event rates, quality of life, and cost-benefit analyses across both cohorts. It is hoped that this study will shed light on the activity of the combined CAPTEM/PRRT treatment in patients with pNETS/mNETS, and inform the design of larger future clinical trials aimed at determining the best treatment for these diseases.
Interventions
Cohort A:
CAPTEM alone: Oral capecitabine 750mg/m2 twice a day, days 1-14 and oral temozolomide 75mg/m2 twice a day, days 10-14, then repeated with capecitabine on days 29-42 and temozolomide on days 38-42 within a 56 day (8w) cycle.
Cohort B:
PRRT alone: 7.8GBq 177Lu Octreotate (Lutate) given intravenously (IV) on day 1 every 8 weeks for 4 cycles (56 day cycle).
Cohort A and B:
PRRT/CAPTEM: 7.8GBq 177Lu Octreotate (Lutate) given intravenously (IV) on day 10 every 8 weeks for 4 cycles, with
Cohort A: CAPTEM alone: Oral capecitabine 750mg/m2 twice a day, days 1-14 and oral temozolomide 75mg/m2 twice a day, days 10-14, then repeated with capecitabine on days 29-42 and temozolomide on days 38-42 within a 56 day (8w) cycle. Cohort B: PRRT alone: 7.8GBq 177Lu Octreotate (Lutate) given intravenously (IV) on day 1 every 8 weeks for 4 cycles (56 day cycle). Cohort A and B: PRRT/CAPTEM: 7.8GBq 177Lu Octreotate (Lutate) given intravenously (IV) on day 10 every 8 weeks for 4 cycles, with concurrent oral capecitabine 750mg/m2twice a day, days 1-14 and temozolomide 75mg/m2 twice a day, days 10-14 every 56 day cycle, up to 4 cycles.
Sponsors
Australasian Gastro-Intestinal Trials Group
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
*Adults greater than or equal to 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 less than or equal to 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 less than or equal to 1.5 x ULN, and Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP) less than or equal to 2.5 x ULN (less than or equal to 5 x ULN for patients with liver metastases)). INR less than or equal to 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.
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.
Outcome results
None listed