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.
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
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.
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....
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
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.
Characterize the safety profile and tolerability of the olaparib + Lu-177-DOTATATE
Determine the maximum tolerated dose (MTD) dose of the combination using the 3+3
dose escalation design.
Measure the Best Overall Response Rate (BOR) by RECIST 1.1 at the MTD dose at
completion of 4 cycles of treatment.
Clinical diagnosis of GEP-NET disease, histologically confirmed to be consistent with
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.
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
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 37 patients to allow for a small number
of inevaluable patients.
If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
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