Randomized Phase II Trial of Postoperative Adjuvant Capecitabine and Temozolomide Versus Observation in High-Risk Pancreatic Neuroendocrine Tumors
Overview
- Phase
- Phase 2
- Intervention
- Capecitabine
- Conditions
- Metastatic Malignant Neoplasm in the Liver
- Sponsor
- SWOG Cancer Research Network
- Enrollment
- 141
- Locations
- 447
- Primary Endpoint
- Recurrence-free survival (RFS)
- Status
- Recruiting
- Last Updated
- 4 months ago
Overview
Brief Summary
This phase II trial studies the effect of capecitabine and temozolomide after surgery in treating patients with high-risk well-differentiated pancreatic neuroendocrine tumors. Chemotherapy drugs, such as capecitabine and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving capecitabine and temozolomide after surgery could prevent or delay the return of cancer in patients with high-risk well-differentiated pancreatic neuroendocrine tumors.
Detailed Description
PRIMARY OBJECTIVE: I. To evaluate recurrence-free survival (RFS) in participants with resected pancreatic neuroendocrine tumors (pNETs) randomized to treatment with capecitabine + temozolomide (CAPTEM) compared to observation only. SECONDARY OBJECTIVES: I. To evaluate overall survival (OS) in participants randomized to treatment with CAPTEM compared to observation only. II. To evaluate the safety and tolerability of CAPTEM compared to observation only. BANKING OBJECTIVE: I. To bank specimens for future correlative studies. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive capecitabine orally (PO) twice daily (BID) on days 1-14 and temozolomide PO once daily (QD) on days 10-14. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. ARM II: Patients undergo surveillance with no active treatment. After completion of study treatment, patients are followed up every 6 months for 3 years and then annually until 5 years from randomization.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participants must have a histologic diagnosis of well-differentiated pancreatic neuroendocrine tumor (pNET) that was resected between 14 and 120 days prior to registration. Participants must have a scan within 90 days prior to registration without evidence of metastatic disease. Acceptable scans are multiphase computed tomography (CT) abdomen, magnetic resonance imaging (MRI) with intravenous (IV) contrast of the abdomen, or positron emission tomography (PET)-CT DOTATATE imaging if the DOTATATE PET-CT included IV iodine contrast for the CT portion of the exam
- •Resection must have been an R0 or R1 per treating investigator's assessment and/or pathology report
- •Ki-67 testing, which is considered part of standard of care in the pathology report, must have been performed between 14 and 90 days prior to registration and the result must be \>= 3% and =\< 55%. Treating investigators are encouraged to contact the S2104 Study Chairs and/or the study pathology chair with questions. If more than one Ki-67 is reported (e.g., primary tumor versus lymph node or metastatic site), the highest one should be considered for the study eligibility criteria
- •Participants with localized resected pNETS must have a Zaidi score of \>= 3 derived by the following factors and points:
- •1 point; symptomatic tumor defined as one of the following:
- •Gastrointestinal bleed
- •Gastrointestinal obstruction
- •Pain from primary tumor prior to surgical resection
- •Pancreatitis
- •2 points; primary pancreas tumor size \> 2 cm
Exclusion Criteria
- •Participants must not have unresected or unablated metastatic disease
- •Participants must not have clinically apparent central nervous system metastases or carcinomatous meningitis
- •Participants must not have received prior neoadjuvant therapy for treatment of pancreatic neuroendocrine tumor. Use of somatostatin analogs prior to surgery is permitted
- •Participants must not have received somatostatin analogs after surgery
- •Participants must not be planning to receive warfarin while on protocol treatment. Other anticoagulants are allowed
- •Participants must not have history of allergic reactions attributed to compounds of similar chemical or biologic composition to temozolomide or capecitabine
- •Participants must not have known absorption issues that would limit the ability to absorb study agents
- •Participants must not have had an arterial thromboembolic event, unstable angina, or myocardial infarction within 12 months prior to registration
- •Participants must not have active or uncontrolled infection
- •Participants must not have serious medical or psychiatric illness that could affect study participation in the judgement of the treating investigator
Arms & Interventions
Arm I (capecitabine, temozolomide)
Patients receive capecitabine PO BID on days 1-14 and temozolomide PO once QD on days 10-14. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Capecitabine
Arm I (capecitabine, temozolomide)
Patients receive capecitabine PO BID on days 1-14 and temozolomide PO once QD on days 10-14. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Temozolomide
Outcomes
Primary Outcomes
Recurrence-free survival (RFS)
Time Frame: From date of randomization to progression/recurrence or death from any cause, assessed up to 5 years
Distribution of RFS in each arm will be estimated using the method of Kaplan-Meier and compared using the stratified log rank test.
Secondary Outcomes
- Overall survival (OS)(From date of registration to date of death due to any cause, assessed up to 5 years)
- Incidence of adverse events(Up to 30 days after completion of treatment)