Lu-177-DOTATATE (Lutathera) in Combination With Olaparib in Inoperable Gastroenteropancreatico Neuroendocrine Tumors (GEP-NET)

Neuroendocrine Tumors Clinical Trial

Official title: Phase I/II Study of Lu-177-DOTATATE (Lutathera) in Combination With Olaparib in Inoperable Gastroenteropancreatico Neuroendocrine Tumors (GEP-NET)

Status Recruiting

Clinical Trial Summary

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:

Participants will be screened under protocol 01-C-0129. They may have a tumor biopsy.

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 Trial Description

Background:

• Neuroendocrine tumors (NETs) of the gastrointestinal tract and pancreas are a rare and heterogeneous, but clinically important, group of neoplasms with unique tumor biology, natural history, and clinical management issues.

• While the treatment of localized NETs is surgical resection, a variety of therapeutic options are available for patients with advanced NETs. These include medical control of excess hormone levels and associated symptoms, cytoreductive surgery for patients with advanced disease, radioembolization, chemoembolization, systemic chemotherapy, interferon, longacting somatostatin analogs, receptor-targeted radionuclide therapy, and or liver transplantation.

• Somatostatin receptors (SSTR) have been shown to be overexpressed in a number of human tumors, including neuroblastoma, prostate cancer, pheochromocytomas, paragangliomas, and NETs, among many others.

• Lu-177-DOTATATE (Lutathera) is a SSTR-agonist agent which emits ionizing radiation that causes DNA damage to its target cells through both direct and indirect mechanisms. In addition, ionizing radiation has also been shown to induce cell death through what is known as the bystander effect, a phenomenon where cellular signaling from irradiated cells towards non-irradiated cells induces cellular damage and eventually death in nearby surrounding cells.

• Olaparib is a PARP inhibitor indicated as monotherapy in patients with deleterious or suspected deleterious germline BRCA-mutated advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. Olaparib has an established safety

profile and it is under investigation in several different cancers.

• The rationale behind using combination therapies in cancer stems from the potential of synergistic mechanisms of action of the involved agents. Olaparib is a PARP-inhibitor which blocks the repair of single-stranded DNA breaks and is especially effective when combined with other agents which induces DNA damage.

Objectives:

• Phase I:

• Characterize the safety profile and tolerability of the olaparib + Lu-177-DOTATATE combination.

• Determine the maximum tolerated dose (MTD) dose of the combination using the 3+3 dose escalation design.

• Phase II:

• Measure the Best Overall Response Rate (BOR) by RECIST 1.1 at the MTD dose at completion of 4 cycles of treatment.

Eligibility:

• Clinical diagnosis of GEP-NET disease, histologically confirmed to be consistent with neuroendocrine tumor.

• Inoperable disease (metastatic, non-candidate for surgery with curative intent, locally advanced into vessels or other critical structures, etc.).

• Age >=18 years.

• Must have presence of SSTR+ disease as documented by positive Ga-68-DOTATATE PET scan within 12 weeks prior to anticipated treatment.

• ECOG Performance Status <= 1.

Design:

• Open-label, single-arm, single-center, phase I/II study evaluating the safety and efficacy of the Lu-177-DOTATATE + olaparib combination in patients with inoperable GEP-NET.

• For phase I, a standard 3+3 design will be used to determine MTD. It is estimated that approximately 15 to 24 patients will be required. Phase II will involve the use of a Simon optimal two-stage design to determine sample size and interim stopping rule.

• Assuming a combination of inevaluable patients or loss-to-follow-up of 10%, up to 24 patients will be accrued to phase I and 15 patients to phase II including the 6 phase I patients at MTD, with a total accrual ceiling of 42 patients to allow for a small number of inevaluable patients. ;

Related Conditions & MeSH terms

• Gastroenteropancreatico Tumors
• Neoplasms
• Neuroendocrine Neoplasms
• Neuroendocrine Tumors

• NCT number: NCT04086485
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Joy Zou, R.N.
• Phone: (240) 760-6153
• Email: zoujh@mail.nih.gov
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: October 3, 2022
• Completion date: January 1, 2026