A parallel group randomised, controlled, multi-centre phase II open label trial with two cohorts testing the combination of capecitabine and temozolomide (CAPTEM) and peptide receptor radionuclide therapy (PRRT) for the treatment of advanced pancreatic or midgut neuroendocrine tumours that are not suitable for surgery.
- Conditions
- Pancreatic Neuroendocrine tumoursMidgut Neuroendocrine tumoursCancer - Neuroendocrine tumour (NET)
- Registration Number
- ACTRN12615000909527
- Lead Sponsor
- Australasian Gastro-Intestinal Trials Group
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 75
*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.
*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
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To determine the rate of progression free survival (PFS) at 12 months in pNETs, and at 24 months in mNETs. [Progression free survival (PFS) will be measured from date of patient randomisation to the date of first evidence of disease progression, the occurrence of new disease or death from any cause. In patients who received treatment on study without a progression date or death, the PFS will be censored on the date of last clinical assessment, tumour assessment or enrolment, whichever is the later event. ]
- Secondary Outcome Measures
Name Time Method