Testing the Addition of An Anti-cancer Drug, M3814 (Peposertib), to the Usual Radiation-Based Treatment (Lutetium Lu 177 Dotatate) for Pancreatic Neuroendocrine Tumors
A Phase 1b Trial of M3814 (Peposertib) in Combination With Lutetium 177 Dotatate for Well-Differentiated Somatostatin Receptor-Positive Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs)
4 other identifiers
interventional
29
1 country
5
Brief Summary
This phase Ib trial is to find out the best dose, possible benefits and/or side effects of peposertib when given together with lutetium Lu 177 dotatate in treating patients with neuroendocrine tumors. Peposertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell formation, so as to help block the formation of growths that may become cancer. Radioactive drugs, such as lutetium Lu 177 dotatate, may deliver radiation directly to tumor cells and not harm normal cells. Adding peposertib to lutetium Lu 177 dotatate may kill more tumor cells.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Jul 2021
Longer than P75 for phase_1
5 active sites
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
February 10, 2021
CompletedFirst Posted
Study publicly available on registry
February 11, 2021
CompletedStudy Start
First participant enrolled
July 22, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 30, 2026
April 17, 2026
April 1, 2026
4.9 years
February 10, 2021
April 16, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Recommended phase 2 dose
Up to 8 weeks
Dose limiting toxicity
Will be assessed by Common Terminology Criteria for Adverse Events version 5.0. The maximum grade of toxicity for each adverse event category of interest will be recorded for each patient and the summary results will be tabulated by category and grade. Will describe all serious (\>= grade 3) toxicity events on a patient-by-patient basis. Frequency and incidence tables of toxicity and adverse events will be generated in the overall patient group and by dose level depending on patient enrollment.
Up to 24 months post-treatment
Secondary Outcomes (3)
Overall response rate
Up to 24 months post-treatment
Progression free survival
Up to 24 months post-treatment
Overall survival
Up to 24 months post-treatment
Other Outcomes (3)
Radiographic expression of somatostatin receptors
Baseline up to 24 months post-treatment
Pharmacokinetic (PK) analysis
Baseline, cycle 1 days 2, 4, 9, 15, and 22
Krenning score from the gallium 68 or copper 64 dotatate
Up to 24 months post-treatment
Study Arms (1)
Treatment (peposertib, lutetium Lu 177 dotatate)
EXPERIMENTALPatients receive peposertib PO QD or BID on days 1-21 and lutetium Lu 177 dotatate IV over 30 minutes on day 1. Treatment repeats every 56 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT/MRI throughout the trial and undergo collection of blood samples on study.
Interventions
Undergo MRI
Undergo CT
Given IV
Given PO
Undergo collection of blood samples
Eligibility Criteria
You may qualify if:
- Patients must have histologically or cytologically confirmed well-differentiated neuroendocrine tumor with positive dotatate scan (gallium 68 or copper 64) (as determined by the site principal investigator \[PI\]) within 6 months before enrollment. Lesions on the dotatate scan (gallium 68 or copper 64) are considered positive if the maximum standard uptake value (SUVmax) is \> 2 times the mean standard uptake value (SUVmean) of normal liver parenchyma. Patients must have the gallium 68 or copper 64 dotatate scans available to send for central review before enrollment
- Patients must have measurable progressive disease based on RECIST criteria, version 1.1, evidenced with CT/MRI scans obtained within 12 months before enrollment
- Failure of at least one prior systemic cancer treatment with somatostatin analogs
- No prior exposure to peptide receptor radionuclide therapy
- Age \>= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
- White blood cell count \>= 2,000/mcL
- Absolute neutrophil count \>= 1,000/mcL
- Platelets \>= 75,000/mcL
- Hemoglobin \>= 8.0 g/dL
- Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) =\< 3 x institutional ULN
- Alkaline phosphatase =\< 3 x institutional ULN
- Glomerular filtration rate (GFR) \>= 50 mL/min/1.73 m\^2 (per the Cockcroft-Gault \[C-G\])
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
- +7 more criteria
You may not qualify if:
- Patients who have had major surgical procedures in the 4 weeks prior to enrollment
- Patients are excluded if they received prior systemic peptide receptor radionuclide therapy (PRRT)-based therapies
- Patients with an inability to swallow oral medications or gastrointestinal disease limiting absorption of oral agents
- Patients who are receiving any other investigational agents
- Known brain metastases, unless these metastases have been treated and stabilized for at least 4 weeks, prior to enrollment in the study. Patients with a history of brain metastases must have either a head CT with contrast or brain MRI to document stable disease prior to enrollment in the study
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to M3814 (peposertib) or lutetium Lu 177 dotatate
- Prior external beam radiotherapy to more than 50% of bone marrow (whole body) will be excluded, as determined by a radiation medicine physicist who will calculate the volume of bone marrow exposure in prior radiotherapy portals divided by the volume of total bone marrow harboring tissues. This ratio must be less than 50 percent
- Patients who cannot discontinue concomitant medications or herbal supplements that are strong inhibitors or strong inducers of cytochrome P450 (CYP) isoenzymes CYP3A4/5, CYP2C9, and CYP2C19. Concomitant use of CYP3A4/5, 1A2, 2B6, 2C8, substrates with a narrow therapeutic index are also excluded. Patients may confer with the study doctor to determine if alternative medications can be used. The following categories of medications and herbal supplements must be discontinued for at least the specified period of time before the patient can be treated:
- Strong inducers of CYP3A4/5, CYP2C9 and CYP2C19: \>= 3 weeks prior to study treatment
- Strong inhibitors of CYP3A4/5, CYP2C9 and CYP2C19: \>= 1 week prior to study treatment
- Substrates of CYP3A4/5, 1A2, 2B6, 2C8, with a narrow therapeutic index: \>= 1 day prior to study treatment Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
- Patients who cannot discontinue concomitant proton-pump inhibitors (PPIs). Patients may confer with the study doctor to determine if such medications can be discontinued. These must be discontinued \>= 5 days prior to study treatment. Patients do not need to discontinue calcium carbonate
- Patients with ongoing active infection or treatment with a live attenuated vaccine within 4 weeks of dosing. In addition, a negative polymerase chain reaction (PCR) test for Covid-19 infection is highly recommended before entering the study, and a close symptom follow up within the study
- Patients with uncontrolled intercurrent illness
- Patients with psychiatric illness/social situations that would limit compliance with study requirements
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (5)
City of Hope Comprehensive Cancer Center
Duarte, California, 91010, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112, United States
Related Publications (1)
Chauhan A, Prieur A, Kolesar J, Arnold S, Payen L, Mahi Y, Vire B, Sands M, Evers BM, Joubert D, Anthony L. hPG80 (Circulating Progastrin), a Novel Blood-Based Biomarker for Detection of Poorly Differentiated Neuroendocrine Carcinoma and Well Differentiated Neuroendocrine Tumors. Cancers (Basel). 2022 Feb 9;14(4):863. doi: 10.3390/cancers14040863.
PMID: 35205614DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Lowell B Anthony
Ohio State University Comprehensive Cancer Center LAO
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 10, 2021
First Posted
February 11, 2021
Study Start
July 22, 2021
Primary Completion (Estimated)
June 30, 2026
Study Completion (Estimated)
June 30, 2026
Last Updated
April 17, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
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