Testing the Addition of a New Anti-cancer Drug, M3814 (Peposertib), to Radiation Therapy for Localized Pancreatic Cancer

Stage III Pancreatic Cancer AJCC v8 Clinical Trial

Official title: A Phase 1/Randomized Phase 2 Study of M3814 (Peposertib) in Combination With Hypofractionated Radiotherapy for the Treatment of Locally Advanced Pancreatic Adenocarcinoma

Status Recruiting

Clinical Trial Summary

This phase I/II trial studies the safety, side effects and best dose of M3814 and to see how well it works when given together with radiation therapy in treating patients with pancreatic cancer that cannot be removed by surgery and has not spread to other parts of the body (localized). M3814 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Giving M3814 and hypofractionated radiation therapy together may be safe, tolerable and more effective than radiation therapy alone in treating patients with localized pancreatic cancer.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To evaluate the safety and tolerability of M3814 (peposertib) in combination with hypofractionated radiotherapy in patients receiving treatment for locally advanced pancreatic adenocarcinoma (LAPC). (Phase I) II. To determine the difference in progression free survival (PFS) between patients with LAPC treated with hypofractionated radiotherapy in combination with M3814 (peposertib) as compared to patients treated with hypofractionated radiotherapy alone. (Phase II)

SECONDARY OBJECTIVES:

I. To observe and record anti-tumor activity. (Phase I) II. To evaluate plasma pharmacokinetic (PK) profiles of M3814 (peposertib) in patients receiving hypofractionated radiotherapy. (Phase I) III. To compare the 2-year overall survival (OS) rate of patients treated with hypofractionated radiotherapy plus M3814 (peposertib) to that of those treated with hypofractionated radiotherapy alone. (Phase II) IV. To compare the objective response rate (ORR) by imaging of patients treated with hypofractionated radiotherapy plus M3814 (peposertib) to that of those treated with hypofractionated radiotherapy alone. (Phase II) V. To compare the disease control rate in patients treated with hypofractionated radiotherapy plus M3814 (peposertib) as compared to those patients treated with hypofractionated radiotherapy alone. (Phase II) VI. To explore gene signature patterns in baseline patient tumor tissues that may suggest response to the combination of M3814 (peposertib) and radiotherapy, as identified on whole exome sequencing and ribonucleic acid (RNA) sequencing (seq). (Phase II)

EXPLORATORY OBJECTIVE:

I. To explore changes in gene signature induced by M3814 (peposertib) and hypofractionated radiotherapy treatment as identified in analysis of cell-free deoxyribonucleic acid (DNA) from the peripheral blood. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of M3814 followed by a phase II study.

PHASE I: Patients undergo hypofractionated radiation therapy for 5 fractions every other day (QOD) over 2 weeks and receive M3814 orally (PO) once daily (QD) for 14 days in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients are randomized to 1 of 2 groups.

GROUP I: Patients undergo hypofractionated radiation therapy for 5 fractions QOD over 2 weeks and receive M3814 PO QD for 14 days in the absence of disease progression or unacceptable toxicity.

GROUP II: Patients undergo hypofractionated radiation therapy for 5 fractions QOD over 2 weeks and receive placebo PO QD for 14 days in the absence of disease progression or unacceptable toxicity.

Patients undergo blood sample collection and tissue biopsy on study. Patients also undergo computed tomography (CT) and magnetic resonance imaging (MRI) during screening and on study.

After completion of study treatment, patients are followed up at 30, 60, and 90 days, and then every 3 months for up to 2 years. ;

Related Conditions & MeSH terms

• Adenocarcinoma
• Locally Advanced Pancreatic Adenocarcinoma
• Locally Advanced Unresectable Pancreatic Adenocarcinoma
• Pancreatic Neoplasms
• Stage II Pancreatic Cancer AJCC v8
• Stage III Pancreatic Cancer AJCC v8
• Unresectable Pancreatic Adenocarcinoma

• NCT number: NCT04172532
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: January 11, 2021
• Completion date: August 1, 2024