Background:
A neuroendocrine tumor is a rare type of tumor. It comes from body cells called neuroendocrine cells. Sometimes, these tumors develop in the gastrointestinal tract and pancreas. Researchers want to find out if a combination of drugs can shrink these tumors.
Objective:
To learn if people with certain neuroendocrine tumors can take a combination of 2 drugs, Lutathera and Olaparib, without having severe side effects, and if this treatment makes the tumors shrink.
Eligibility:
Adults 18 and older who have a neuroendocrine tumor in the pancreas or intestine that cannot be cured by surgery and has somatostatin receptors on the cells.
Design:
Eligible participants will get Lutathera through an intravenous (IV) infusion every 8 weeks for 4 cycles. One cycle is 8 weeks. Each cycle includes a follow-up visit at week 4. For the IV, a small plastic tube is put into an arm vein.
Participants will also take Olaparib by mouth twice a day for 4 weeks of each cycle. They will use a medicine diary to track the doses.
During the study, participants will have physical exams. They will have blood and urine tests. They will fill out questionnaires about their general well-being and function. Their heart function will be tested. They will have scans of their chest, abdomen, and pelvis. One type of scan will use an IV infusion of a radioactive tracer.
Participants will have a follow-up visit about 4 weeks after treatment ends. Then they will have follow-up visits every 12 weeks for 3 years. Then they will have yearly phone calls.
Clinical diagnosis of GEP-NET disease, histologically consistent with neuroendocrine tumor.
Inoperable disease (metastatic, non-candidate for surgery with curative intent, locally advanced into vessels or other critical structures, etc.)
Patients on somatostatin analogue therapy (e.g., but not only limited to sandostatin or lanreotide therapy) must have initiated and been on a consistent dose of therapy for at least 3 months prior to study enrollment.
Patients on short-term octreotide must have dose held for 24 hours without octreotide because this is necessary for study Lu-177-DOTATATE therapy.
Patients who have any GEP-NET lesions that are negative by Ga-68-DOTATATE-PET imaging but positive by FDG-PET imaging, unless they have progressed on at least one other line of prior systemic treatment (such as chemotherapy or tyrosine kinase inhibitor) and the majority of their tumor lesions are Ga-68-DOTATATE-avid.
Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with study drugs, breastfeeding should be discontinued if the mother is treated with study drugs.
Other known co-existing malignancies except non-melanoma skin cancer and carcinoma in situ of the uterine cervix, unless definitively treated and proven no evidence of recurrence for 5 years.
Patients who are receiving any other investigational agents.
Sequential
Lu-177-DOTATATE
DrugLu-177-DOTATATE will be given by IV every 8 (+/-2) weeks for a total of 4 administrations
Olaparib
DrugOlaparib is given as a pill taken orally and is to be taken twice a day, starting from 2 days before the first administration of Lu-177-DOTATATE until 4 weeks after the last administration
Ga dotatate scanning
Diagnostic testGa68-DOTATATE PET/CT scan will be done at baseline, at week 32, then every 24 weeks in followup period.
FDG-PET scanning
Diagnostic testF18-FDG PET/CT scan will be done at baseline, at week 32, then every 24 weeks in followup period.
Amino Acid infusion
DrugConcomitant administration of an IV infusion of an amino acid (AA) solution will also be done for renal protection. The AA infusion will begin at least 30-60 minutes prior to injection of Lu-177-DOTATATE and will continue during and after the Lutathera infusion until the entire prescribed amount is infused.
Phase 1: Maximum Tolerated Dose
Depending on what the speed of dose escalation and the final MTD dose, it is estimated that for 4 dose levels with up to 6 patients at each level, approximately 12 to 24 patients will be required for the phase I portion of the study. Standard 3+3 design will be used.
Phase 2: Overall Response Rate
Proportion of patients who have a partial or complete response to therapy.
Phase 2: PFS and OS of BRCA participants
Preliminary evidence of exceptional efficacy of the combination at MTD in a sub-cohort of participants with BRCA mutation. Participants from the BRCA cohort will be analyzed together with other phase 2 participants as well as separately using descriptive data only.
Phase 1: BOR and PFS
Preliminary information on the BOR will be presented as a percentage with 95% confidence intervals. Only evaluate patients will be included. Kaplan-Meier curves of PFS will be constructed. Median PFS will be reported with 95% confidence intervals.
Phase 2: PFS and OS
Kaplan-Meier curves of PFS and OS will be constructed. Median PFS and OS will be reported with 95% confidence intervals.
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