Lu-177-DOTATATE (Lutathera) in Combination With Olaparib in Inoperable Gastroenteropancreatico Neuroendocrine Tumors (GEP-NET)
Phase I/II Study of Lu-177-DOTATATE (Lutathera) in Combination With Olaparib in Inoperable Gastroenteropancreatico Neuroendocrine Tumors (GEP-NET)
2 other identifiers
interventional
56
1 country
1
Brief 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: 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Oct 2022
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 10, 2019
CompletedFirst Posted
Study publicly available on registry
September 11, 2019
CompletedStudy Start
First participant enrolled
October 3, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
January 1, 2028
April 1, 2026
December 10, 2025
4.7 years
September 10, 2019
March 31, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
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.
End of cycle 1
Phase 2: Overall Response Rate
Proportion of patients who have a partial or complete response to therapy.
At disease progression
Secondary Outcomes (3)
Phase 2: PFS and OS of BRCA participants
Disease progression
Phase 1: BOR and PFS
Disease progression
Phase 2: PFS and OS
Death
Study Arms (2)
1/Lu-177-DOTATATE + Olaparib escalation
EXPERIMENTALLu-177-DOTATATE and escalating doses of olaparib to determine the maximum-tolerated dose (MTD)
2/Lu-177-DOTATATE + Olaparib fixed dose
EXPERIMENTALLu-177-DOTATATE and olaparib at the MTD
Interventions
Lu-177-DOTATATE will be given by IV every 8 (+/-2) weeks for a total of 4 administrations
Olaparib 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
Ga68-DOTATATE PET/CT scan will be done at baseline, at week 32, then every 24 weeks in followup period.
F18-FDG PET/CT scan will be done at baseline, at week 32, then every 24 weeks in followup period.
Concomitant 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.
Eligibility Criteria
You may qualify if:
- 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.)
- NOTE: Presence of at least one non-irradiated index lesion (Phase II only).
- 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.
- Age \>=18 years. Because no dosing or adverse event data are currently available on the use of Lu-177-DOTATATE in combination with olaparib in patients \<18 years of age, children are excluded from this study, but may be eligible for future pediatric trials.
- Must have presence of somatostatin receptors (SSTR) positive disease as documented by positive Ga-68-DOTATATE PET scan within 12 weeks prior to enrollment. NOTE: Positivity of Ga-68-DOTATATE PET scan is defined as having at least one RECIST 1.1 measurable lesion that has an SUV higher than or equal to liver and is qualitatively higher and distinguishable from background activity.
- Known BRCA mutation status (Cohort 3 only).
- Progressive disease by RECIST 1.1, as compared to previous anatomic imaging no more than 36 months from the date of study enrollment, with at least 1 measurable lesion by RECIST 1.1.
- ECOG Performance Status of \<=1.
- Patients must have normal organ and bone marrow function measured within 28 days prior to enrollment as defined below:
- Hemoglobin \>= 10.0 g/dL with no blood transfusion in the past 28 days
- Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L
- Platelet count \>= 100 x 10\^9/L
- Total bilirubin \<= 1.5 x institutional upper limit of normal (ULN)
- +25 more criteria
You may not qualify if:
- 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.
- Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 4 weeks prior to study enrollment.
- Patients with persistent toxicities (\>= CTCAE grade 2) with the exception of alopecia, caused by previous cancer therapy and toxicities deemed irreversible/stable expected to interfere with study drug administration in the opinion of the Principal Investigator.
- Patient's weight exceeding PET table tolerance (\> 400 lbs).
- Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, hypertension (\>180/110), arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Patients with symptomatic, uncontrolled brain metastases. NOTE: Patients with previously treated brain metastases are eligible if asymptomatic and may be on a stable dose of corticosteroids as long as these were started at least 4 weeks prior to treatment.
- Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease by imaging and clinical assessment as assessed by the treating investigator for 28 days before enrollment.
- Concomitant use of known strong or moderate CYP3A inhibitors within 2 weeks before enrollment.
- Concomitant use of known strong or moderate CYP3A inducers within 5 weeks (for enzalutamide or phenobarbital) and 3 weeks for other agents before enrollment.
- Patients that have had major surgery within 4 weeks prior to study enrollment and have not recovered from any effects of any major surgery.
- Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
- Previous allogeneic hematopoietic stem cell transplant, allogeneic bone marrow transplant or double umbilical cord blood transplant (duCBT).
- +8 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Related Publications (1)
Haque F, Carrasquillo JA, Turkbey EB, Mena E, Lindenberg L, Eclarinal PC, Nilubol N, Choyke PL, Floudas CS, Lin FI, Turkbey B, Harmon SA. An automated pheochromocytoma and paraganglioma lesion segmentation AI-model at whole-body 68Ga- DOTATATE PET/CT. EJNMMI Res. 2024 Nov 5;14(1):103. doi: 10.1186/s13550-024-01168-5.
PMID: 39500789DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Frank I Lin, M.D.
National Cancer Institute (NCI)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 10, 2019
First Posted
September 11, 2019
Study Start
October 3, 2022
Primary Completion (Estimated)
July 1, 2027
Study Completion (Estimated)
January 1, 2028
Last Updated
April 1, 2026
Record last verified: 2025-12-10
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Clinical data available during the study and indefinitely.@@@@@@@@@@@@Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active.
- Access Criteria
- Clinical data will be made available via subscription to BTRIS and with the permission of the study PI. @@@@@@@@@@@@Genomic data are made available via dbGaP through requests to the data custodians.
All IPD recorded in the medical record will be shared with intramural investigators upon request. In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.