Spots Global Cancer Trial Database for Testing the Addition of An Anti-cancer Drug, M3814 (Peposertib), to the Usual Radiation-Based Treatment (Lutetium Lu 177 Dotatate) for Pancreatic Neuroendocrine Tumors

Study Description

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.

Detailed Description: PRIMARY OBJECTIVE: I. To evaluate the safety and to determine the recommended phase 2 dose (RP2D) of lutetium Lu 177 dotatate in combination with M3814 (peposertib). SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity. II. To determine the overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 at 4, 8, and 12 months post-therapy. III. To measure duration of response (DOR) associated with the combination. IV. To evaluate progression-free survival (PFS). CORRELATIVE OBJECTIVES: I. Measure the somatostatin receptor uptake on gallium 68 dotatate or Copper 64 dotatate at baseline. II. Perform lutetium Lu 177 dotatate dosimetry. III. Determine the pharmacokinetic (PK) parameters of M3814 (peposertib). IV. Describe the tumor molecular profile using whole exome sequencing (WES) and ribonucleic acid (RNA) sequencing (RNAseq) and correlate it with treatment outcome. V. Collect plasma for circulating tumor deoxyribonucleic acid (DNA) (ctDNA) assessment. VI. Collect blood for biobanking and future correlative studies. VII. Measure association of overall response rate with gallium 68 dotatate-positron emission tomography (PET)/computed tomography (CT) or Copper 64 dotatate measurements and Krenning score. OUTLINE: This is a dose-escalation study of peposertib followed by a dose-expansion study. Patients receive peposertib orally (PO) once daily (QD) or twice daily (BID) on days 1-21 and lutetium Lu 177 dotatate intravenously (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/magnetic resonance imaging (MRI) throughout the trial and undergo collection of blood samples on study. After completion of study treatment, patients are followed up every 4 months for 24 months.

Keywords

Eligibility

Minimum Age: 18 Years

Eligible Ages: ADULT, OLDER_ADULT

Sex: ALL

Healthy Volunteers: No

Locations

Contact Details

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