This phase II trial compares capecitabine and temozolomide to lutetium Lu 177 dotatate for the treatment of pancreatic neuroendocrine tumors that have spread to other parts of the body (advanced) or are not able to be removed by surgery (unresectable). 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. Radioactive drugs, such as lutetium Lu 177 dotatate, may carry radiation directly to tumor cells and may reduce harm to normal cells. The purpose of this study is to find out whether capecitabine and temozolomide or lutetium Lu 177 dotatate may kill more tumor cells in patients with advanced pancreatic neuroendocrine tumors.
This phase II trial compares capecitabine and temozolomide to lutetium Lu 177 dotatate for the treatment of pancreatic neuroendocrine tumors that have spread to other parts of the body (advanced) or are not able to be removed by surgery (unresectable). 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. Radioactive drugs, such as lutetium Lu 177 dotatate, may carry radiation directly to tumor cells and may reduce harm to normal cells. The purpose of this study is to find out whether capecitabine and temozolomide or lutetium Lu 177 dotatate may kill more tumor cells in patients with advanced pancreatic neuroendocrine tumors. The primary and secondary objectives of the study: PRIMARY OBJECTIVE: I. To determine the differences in median progression-free survival (PFS) for lutetium Lu 177 dotatate peptide receptor radionuclide therapy (PRRT) when compared to capecitabine and temozolomide (CAPTEM) in patients with locally advanced or metastatic progressive, well-differentiated pancreatic neuroendocrine tumors (pNETs). SECONDARY OBJECTIVES: I. To evaluate and compare the overall survival (OS) of patients receiving lutetium Lu 177 dotatate versus (vs.) CAPTEM. II. To evaluate and compare time to response, time to maximum response, and overall response rates (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 between both arms. III. To evaluate and compare duration of response and time to progression among both arms. IV. To evaluate and compare treatment related toxicities between the arms. V. To compare global health status/quality of life as measured with the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30 from baseline through 18 months between patients with pNET treated with lutetium Lu 177 dotatate PRRT versus capecitabine and temozolomide. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive lutetium Lu 177 dotatate intravenously (IV) over 30 minutes on day 1. Treatment repeats every 8 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive capecitabine orally (PO) twice daily (BID) days 1-14 and temozolomide PO once daily (QD) on days 10-14. Treatment repeats every 4 weeks for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
31
Fairbanks Memorial Hospital
Fairbanks, Alaska, United States
Mayo Clinic Hospital in Arizona
Phoenix, Arizona, United States
Tower Cancer Research Foundation
Beverly Hills, California, United States
Epic Care-Dublin
Dublin, California, United States
Bay Area Breast Surgeons Inc
Emeryville, California, United States
Progression free survival (PFS)
Progression free survival (PFS) will be compared between the two treatment arms using Kaplan-Meier methods. The hazard ratio (HR) and median PFSwill be estimated along with corresponding 95% confidence intervals.
Time frame: Up to 8 years from randomization
Progression Free Survival (PFS) at 2 years
Kaplan-Meier methodology will be used to estimate the PFS rate at 2 years.
Time frame: At 2 years from randomization
Progression Free Survival (PFS) at 3 years
Kaplan-Meier methodology will be used to estimate the PFS rate at 3 years.
Time frame: At 3 years from randomization
Time to progression (TTP)
Kaplan-Meier methodology will be used to estimate the median time to progression (TTP).
Time frame: Up to 8 years from randomization
Overall survival (OS)
Kaplan-Meier methodology will be used to estimate the median overall survival (OS). OS is defined as randomization to the time of death due to any cause (or censored at the time of last contact for surviving patients and those lost to follow-up).
Time frame: Up to 8 years from study registration
Objective response rate (ORR)
The response rate (percentage) is the percent of patients whose best response was Complete Response (CR) or Partial Response (PR) as defined by RECIST 1.1 criteria. Percentage of successes will be estimated by 100 times the number of successes divided by the total number of evaluable patients. Response rates (including complete and partial response) will be tested using Fisher's exact test.
Time frame: Up to 8 years from randomization
Time-to response
Kaplan-Meier methodology will be used to estimate the median time-to-response. Time-to-response will be defined as the time from randomization to the first tumor response, for those patients having achieved an objective response.
Time frame: Up to 8 years from randomization
Duration of response
Kaplan-Meier methodology will be used to estimate the median duration of response. Duration of response will be defined as the time from first assessment with documented response (PR or CR) to the time of progression and/or death. Patients who are still responding as of their last evaluation will be censored at the time point. If we observed documented deaths without progression, we will further evaluate this endpoint with death without progression treated as a competing risk.
Time frame: Up to 8 years from randomization
Incidence of adverse events
Patients will be evaluated for adverse events using the National Cancer Institute Common Toxicity Criteria for Adverse Events version 5.0. The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported.
Time frame: Up to 8 years from randomization
Change in Overall Health Question (Q29) from the EORTC QLQ-C30 questionnaire
To evaluate between-arm differences in patient-reported global health status from baseline through 18 months, the area under the curve will be calculated as a summary statistic for each arm based on estimates from a mixed model for patient-reported global health status/quality of life as assessed by the EORTC QLQ-C30 at baseline, 3, 6, 12, and 18 months.
Time frame: At baseline up to 18 months
Change in Overall Quality of Life Question (Q30) from the EORTC QLQ-C30 questionnaire
To evaluate between-arm differences in patient-reported quality of life from baseline through 18 months, the area under the curve will be calculated as a summary statistic for each arm based on estimates from a mixed model for patient-reported global health status/quality of life as assessed by the EORTC QLQ-C30 at baseline, 3, 6, 12, and 18 months.
Time frame: At baseline up to 18 months
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Epic Care Partners in Cancer Care
Emeryville, California, United States
Cedars Sinai Medical Center
Los Angeles, California, United States
Contra Costa Regional Medical Center
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Bay Area Tumor Institute
Oakland, California, United States
Torrance Memorial Physician Network - Cancer Care
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