Multi-agent Low Dose Chemotherapy GAX-CI Followed by Olaparib and Pembro in Metastatic Pancreatic Ductal Cancer.

NCT ID: NCT04753879

Last Updated: 2025-12-04

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-29
• Study Completion Date: 2029-12-01

Brief Summary

The purpose of this study is to evaluate the safety and clinical activity of maintenance olaparib and pembrolizumab following multi-agent, low dose chemotherapy with gemcitabine, nab-paclitaxel, capecitabine, cisplatin, and irinotecan (GAX-CI) in patients with untreated metastatic pancreatic ductal cancer.

Conditions

Metastatic Pancreatic Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Nab-paclitaxel, Gemcitabine , Cisplatin, Irinotecan, Capecitabine

Maintenance of Pembrolizumab and Olaparib

Group Type: EXPERIMENTAL

Nab-paclitaxel

Intervention Type: DRUG

1. Patients will receive treatment Day 1 and Day 15 of each cycle (28 days).

2. Nab-paclitaxel (80 mg/m2) will be administered IV on Day 1 and Day 15 (28 day cycle).

3. Other Name: Abraxane

Gemcitabine

Intervention Type: DRUG

1. Patients will receive treatment Day 1 and Day 15 of each cycle (28 days).

2. Gemcitabine (500mg/m2) will be administered IV on Day 1 and Day 15 (28 day cycle).

3. Other Name: Gemzar

Cisplatin

Intervention Type: DRUG

1. Patients will receive treatment Day 1 and Day 15 of each cycle (28 days).

2. Cisplatin (20mg/m2) will be administered IV on Day 1 and Day 15 (28 day cycle).

3. Other Name: N/A

Irinotecan

Intervention Type: DRUG

1. Patients will receive treatment Day 1 and Day 15 of each cycle (28 days).

2. Irinotecan (20 mg/m2) will be administered IV on Day 1 and Day 15 (28 day cycle).

3. Other Name: N/A

Capecitabine

Intervention Type: DRUG

1. Patients will receive treatment Day 1-7 and Day 15-21 of each cycle (28 days).

2. Capecitabine (500 mg) will be administered orally twice a day on days 1-7 and 15-21 of each cycle (28 days).

3. Other Name: Xeloda

Pembrolizumab

Intervention Type: DRUG

1. Patients will receive treatment Day 1 every other cycle (every 6 weeks) (28 days) during maintenance phase.

2. Pembrolizumab (400 mg) will be administered IV on day 1 every other cycle (every 6 weeks).

3. Other Name: MK-3475; Keytruda

Olaparib

Intervention Type: DRUG

1. Patients will receive treatment on Days 1-21 during the maintenance phase.

2. Olaparib (300 mg) will be administered orally twice a day on Days 1- 21 of each cycle (28 days).

3. Other Name: Lynparza

Interventions

Nab-paclitaxel

1. Patients will receive treatment Day 1 and Day 15 of each cycle (28 days).

2. Nab-paclitaxel (80 mg/m2) will be administered IV on Day 1 and Day 15 (28 day cycle).

3. Other Name: Abraxane

Intervention Type: DRUG

Gemcitabine

1. Patients will receive treatment Day 1 and Day 15 of each cycle (28 days).

2. Gemcitabine (500mg/m2) will be administered IV on Day 1 and Day 15 (28 day cycle).

3. Other Name: Gemzar

Intervention Type: DRUG

Cisplatin

1. Patients will receive treatment Day 1 and Day 15 of each cycle (28 days).

2. Cisplatin (20mg/m2) will be administered IV on Day 1 and Day 15 (28 day cycle).

3. Other Name: N/A

Intervention Type: DRUG

Irinotecan

1. Patients will receive treatment Day 1 and Day 15 of each cycle (28 days).

2. Irinotecan (20 mg/m2) will be administered IV on Day 1 and Day 15 (28 day cycle).

3. Other Name: N/A

Intervention Type: DRUG

Capecitabine

1. Patients will receive treatment Day 1-7 and Day 15-21 of each cycle (28 days).

2. Capecitabine (500 mg) will be administered orally twice a day on days 1-7 and 15-21 of each cycle (28 days).

3. Other Name: Xeloda

Intervention Type: DRUG

Pembrolizumab

1. Patients will receive treatment Day 1 every other cycle (every 6 weeks) (28 days) during maintenance phase.

2. Pembrolizumab (400 mg) will be administered IV on day 1 every other cycle (every 6 weeks).

3. Other Name: MK-3475; Keytruda

Intervention Type: DRUG

Olaparib

1. Patients will receive treatment on Days 1-21 during the maintenance phase.

2. Olaparib (300 mg) will be administered orally twice a day on Days 1- 21 of each cycle (28 days).

3. Other Name: Lynparza

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Cohort 1 - Subject has stable disease as measured by RECIST 1.1 or iRECIST after 6 cycles of GAX-CI.
• Cohort 2 - Subject has progressive disease as measured by RECIST 1.1 and iRECIST prior to 6 cycles of GAX-CI.
• Ability to understand and willingness to sign a written informed consent document.
• Age ≥18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Have metastatic histologically or cytologically-proven ductal pancreatic cancer.
• Patients must not have received prior treatment for pancreatic cancer.
• Have measurable disease based on RECIST 1.1.
• Willing to have to a tumor biopsy.
• Patients must have adequate organ and marrow function defined by study - specified laboratory tests.
• Woman of childbearing potential must have a negative pregnancy test and follow contraceptive guidelines as defined per protocol.
• Men must use acceptable form of birth control while on study.
• Participant understands the study regimen, its requirements, risks and discomforts, competent to report AE, understand the drug dosing schedule and use of medications to control AE.

Exclusion Criteria

• Patients who will be considered for surgery are ineligible.
• Had chemotherapy within 5 years prior to study treatment.
• Have received any investigational drugs within 28 days prior to study treatment.
• Had surgery within 28 days of dosing of investigational agent.
• Has history of central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Require any antineoplastic therapy.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent.
• Has received prior therapy with gemcitabine, nab-paclitaxel, capecitabine, cisplatin, irinotecan, or PARP inhibitor.
• Hypersensitivity reaction to any monoclonal antibody.
• Is taking a moderate or strong CYP3A inhibitor.
• Has uncontrolled acute or chronic medical illness.
• Has known additional malignancy that is progressing and requires active treatment.
• Has received radiotherapy for pancreatic cancer.
• Have received any live vaccine or live-attenuated, any allergen hyposensitization therapy, growth factors or major surgery within 30 days prior to study treatment.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
• Has active autoimmune disease.
• Has an active known or suspected autoimmune disease or is receiving chronic systemic steroid therapy within 7 days prior to the first dose of study drug.
• Prior tissue or organ allograft or allogeneic bone marrow transplantation.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Requirement for daily supplemental oxygen.
• Patients with a history of (non-infectious) pneumonitis/interstitial lung disease that requires steroids.
• Subject with clinically significant wound.
• Has a confirmed history of encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent.
• Infection with HIV.
• Has active Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or Hepatitis C virus (defined as hepatitis C virus (HCV) RNA [qualitative] is detected) infection. Patients who are Hepatitis C antibody positive and viral load negative will be permitted to enroll.
• Has uncontrolled infection.
• Unwilling to have blood drawn.
• Has known psychiatric or substance use disorder that would interfere with cooperation with the requirements of the trial.
• Woman who are pregnant or breastfeeding.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dung Le, MD

Role: PRINCIPAL_INVESTIGATOR

SKCCC Johns Hopkins Medical Institution

Locations

Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Colleen Apostal, RN

Role: CONTACT

GIClinicaltrials@jhmi.edu

410-614-3644

Other Identifiers

IRB00267980

Identifier Type: OTHER

Identifier Source: secondary_id

J2112

Identifier Type: -

Identifier Source: org_study_id