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

NCT04753879 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: J2112IRB00267980
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

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

Keywords

PARP; Gemcitabine; Nab-paclitaxel; Capecitabine; Cisplatin; Irinotecan; Olaparib; Pembrolizumab; Immunotherapy; PD-L1 (receptor blocking antibody); Anti-PD-L1; Monoclonal Antibodies; Metastatic pancreatic cancer

Outcome Measures

Primary Outcomes (2)

• Progression-free Survival (PFS) after 6 months according to RECIST 1.1 criteria.

  PFS is defined as the 6 month from the date of randomization to disease progression (progressive disease \[PD\] or relapse from complete response \[CR\] as assessed using RECIST 1.1 criteria) or death due to any cause. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =\>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is \>20% increase in sum of diameters of target lesions, Stable Disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions.

  6 Months

• Progression-free Survival (PFS) after 6 months according to IRECIST criteria.

  PFS is defined as the 6 month from the date of randomization to disease progression (progressive disease \[PD\] or relapse from complete response \[CR\] as assessed using iRECIST criteria) or death due to any cause. Per iRECIST criteria, CR = disappearance of all target lesions, Partial Response (PR) is =\>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is \>20% increase in sum of diameters of target lesions, Stable Disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions.

  6 months

Secondary Outcomes (1)

• Number of participants experiencing grade 3 or above drug-related toxicities

  4 years

Study Arms (1)

Nab-paclitaxel, Gemcitabine , Cisplatin, Irinotecan, Capecitabine

EXPERIMENTAL

Maintenance of Pembrolizumab and Olaparib

Drug: Nab-paclitaxel; Drug: Gemcitabine; Drug: Cisplatin; Drug: Irinotecan; Drug: Capecitabine; Drug: Pembrolizumab; Drug: Olaparib

Interventions

Nab-paclitaxel 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

Nab-paclitaxel, Gemcitabine , Cisplatin, Irinotecan, Capecitabine

Cisplatin 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

Nab-paclitaxel, Gemcitabine , Cisplatin, Irinotecan, Capecitabine

Gemcitabine 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

Nab-paclitaxel, Gemcitabine , Cisplatin, Irinotecan, Capecitabine

Irinotecan 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

Nab-paclitaxel, Gemcitabine , Cisplatin, Irinotecan, Capecitabine

Capecitabine 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

Nab-paclitaxel, Gemcitabine , Cisplatin, Irinotecan, Capecitabine

Pembrolizumab 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

Nab-paclitaxel, Gemcitabine , Cisplatin, Irinotecan, Capecitabine

Olaparib 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

Nab-paclitaxel, Gemcitabine , Cisplatin, Irinotecan, Capecitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: collaborator
• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21231, United States

RECRUITING

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

130-nm albumin-bound paclitaxel; Gemcitabine; Cisplatin; Irinotecan; Capecitabine; pembrolizumab; olaparib

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Camptothecin; Alkaloids; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Dung Le, MD

  SKCCC Johns Hopkins Medical Institution

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Colleen Apostal, RN

CONTACT

410-614-3644; GIClinicaltrials@jhmi.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2021
• First Posted: February 15, 2021
• Study Start: September 29, 2021
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2029
• Last Updated: December 4, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)