Multi-agent Chemotherapy + Olaparib and Pembrolizumab for Pancreatic Cancer

Recruiting at 1 trial location

Overseen By Colleen Apostal, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must not be taking: CYP3A inhibitors

Disqualifiers: CNS metastases, Autoimmune disease, HIV, Hepatitis B, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

38 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot take certain drugs like moderate or strong CYP3A inhibitors. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drugs used in the Multi-agent Chemotherapy + Olaparib and Pembrolizumab for Pancreatic Cancer trial?

Research shows that combining nab-paclitaxel (a form of chemotherapy) with gemcitabine improves survival in patients with advanced pancreatic cancer compared to using gemcitabine alone. ^{1 2 3 4 5}

Is the combination of nab-paclitaxel and gemcitabine safe for treating pancreatic cancer?

The combination of nab-paclitaxel and gemcitabine has been studied for pancreatic cancer, and safety data from these studies suggest it is generally safe for use in humans, although specific side effects and risks should be discussed with a healthcare provider. ^{2 6 7 8 9}

What makes the multi-agent chemotherapy with Olaparib and Pembrolizumab unique for pancreatic cancer?

This treatment combines multiple chemotherapy drugs with Olaparib, a targeted therapy, and Pembrolizumab, an immunotherapy, which is unique because it integrates different mechanisms to attack cancer cells, potentially improving outcomes compared to standard chemotherapy alone. ^{1 3 4 10 11}

Research Team

Dung Le, MD

Principal Investigator

SKCCC Johns Hopkins Medical Institution

Eligibility Criteria

This trial is for adults with untreated metastatic pancreatic ductal cancer who have stable or progressive disease after chemotherapy. They must be in good physical condition, understand the study, and agree to use birth control. Excluded are those planning surgery, recent chemo or investigational drug users, with autoimmune diseases, uncontrolled illnesses, certain prior treatments or allergies to monoclonal antibodies.

Inclusion Criteria

I am willing to undergo a tumor biopsy.

My cancer has worsened despite treatment before completing 6 cycles of GAX-CI.

I have not had any treatment for pancreatic cancer.

Exclusion Criteria

I am currently taking medication that strongly affects liver enzymes.

I haven't had any live vaccines, allergy treatments, growth factors, or major surgery in the last 30 days.

You have had a bad reaction to any kind of monoclonal antibody.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy

Participants receive multi-agent, low dose chemotherapy with gemcitabine, nab-paclitaxel, capecitabine, cisplatin, and irinotecan (GAX-CI)

6 months

Maintenance

Participants receive maintenance therapy with olaparib and pembrolizumab

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 years

Treatment Details

Interventions

• Capecitabine
• Cisplatin
• Gemcitabine
• Irinotecan
• Nab-paclitaxel
• Olaparib
• Pembrolizumab

Trial Overview The trial tests maintenance therapy with Olaparib and Pembrolizumab following a multi-agent low dose chemotherapy regimen (GAX-CI) consisting of Gemcitabine, Nab-paclitaxel, Capecitabine, Cisplatin and Irinotecan in patients who haven't been treated before for their pancreatic cancer.

Participant Groups

Group I: Nab-paclitaxel, Gemcitabine , Cisplatin, Irinotecan, Capecitabine Experimental Treatment 7 Interventions

Maintenance of Pembrolizumab and Olaparib

Capecitabine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in United States as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Canada as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Japan as Xeloda for:

• Colorectal cancer
• Breast cancer

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

A study of 5465 patients with advanced pancreatic cancer in Ontario showed that the introduction of new chemotherapy regimens, GEMNAB and FOLFIRINOX, significantly improved overall survival rates over time, with median survival increasing from 5.6 months to 7.6 months between 2008 and 2018.

FOLFIRINOX was found to provide better overall survival compared to GEMNAB, particularly in younger and healthier patients, while GEMNAB still showed improved survival compared to the older standard treatment, gemcitabine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Association of Drug-Funding Reimbursement With Survival Outcomes and Use of New Systemic Therapies Among Patients With Advanced Pancreatic Cancer. Raphael, MJ., Raskin, W., Habbous, S., et al.[2023]

In a phase 3 trial involving 861 patients with metastatic pancreatic cancer, the combination of nab-paclitaxel and gemcitabine significantly improved overall survival (8.5 months) compared to gemcitabine alone (6.7 months), with a hazard ratio for death of 0.72, indicating a 28% reduction in the risk of death.

The combination therapy also resulted in better progression-free survival (5.5 months vs. 3.7 months) and a higher overall response rate (23% vs. 7%), although it was associated with increased rates of adverse events like neutropenia and neuropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. Von Hoff, DD., Ervin, T., Arena, FP., et al.[2022]

In a small study of 3 patients with metastatic ampullary and duodenal adenocarcinoma who had previously failed standard chemotherapy, treatment with nab-paclitaxel and gemcitabine (with or without cisplatin) resulted in excellent tumor responses and over a year of progression-free survival.

All patients showed significant reductions in tumor markers and have survived for 2-3 years since their diagnosis, suggesting that nab-paclitaxel combined with gemcitabine could be a promising salvage therapy for these difficult-to-treat cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durable response for ampullary and duodenal adenocarcinoma with a nab-paclitaxel plus gemcitabine ± cisplatin combination. Cen, P., Wray, CJ., Zhang, S., et al.[2022]

The introduction of FOLFIRINOX and gemcitabine plus nab-paclitaxel therapy significantly improved treatment outcomes for metastatic pancreatic cancer, with response rates increasing from 7.8% to 28.4% after these therapies were introduced.

Patients treated with the newer therapies experienced longer median progression-free survival (3.1 months to 5.4 months) and median overall survival (6.7 months to 10.2 months), indicating a substantial benefit in daily clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improvement of Treatment Outcomes for Metastatic Pancreatic Cancer: A Real-world Data Analysis. Sasaki, T., Kanata, R., Yamada, I., et al.[2022]

In a study of 485 patients with localized pancreatic cancer, those treated with FOLFIRINOX showed higher rates of partial response according to RECIST criteria compared to those treated with gemcitabine plus nab-paclitaxel (GA), indicating better initial tumor response.

Despite the higher response rates and more frequent surgeries (pancreatectomy) in the FOLFIRINOX group, overall survival rates were similar between the two treatment regimens, suggesting that while FOLFIRINOX may be more effective in shrinking tumors, it does not necessarily lead to longer survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response and Survival Associated With First-line FOLFIRINOX vs Gemcitabine and nab-Paclitaxel Chemotherapy for Localized Pancreatic Ductal Adenocarcinoma. Perri, G., Prakash, L., Qiao, W., et al.[2022]

Nab-paclitaxel plus gemcitabine (nab-P/Gem) is an effective first-line treatment for metastatic pancreatic cancer, with median overall survival rates ranging from 8.7 to 13.5 months across various studies involving a diverse patient population.

The combination of nab-P/Gem with additional agents is being actively researched, showing promise for improving outcomes in advanced pancreatic cancer, with median overall survival extending up to 17 months in some cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

nab-Paclitaxel for the treatment of pancreatic cancer. Kim, G.[2023]

In a trial involving 84 patients with advanced non-small-cell lung cancer, the efficacy of weekly nab-paclitaxel plus cisplatin was found to be similar to that of gemcitabine plus cisplatin, with median progression-free survival of 4.8 months for nab-TP and 5.2 months for GP.

Nab-paclitaxel showed improved overall survival in patients with EGFR mutations (26.7 months) and those with a performance status of 0 (23.5 months) compared to gemcitabine, indicating potential benefits in specific patient subgroups while maintaining comparable safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weekly albumin-bound paclitaxel/cisplatin versus gemcitabine/cisplatin as first-line therapy for patients with advanced non-small-cell lung cancer: A phase II open-label clinical study. Qin, S., Yu, H., Wu, X., et al.[2022]

In a study involving 866 patients with resected pancreatic ductal adenocarcinoma, the combination of nab-paclitaxel and gemcitabine showed a significant improvement in overall survival (OS) compared to gemcitabine alone, with a median OS of 41.8 months versus 37.7 months, respectively.

Although the primary endpoint of disease-free survival (DFS) was not significantly improved with nab-paclitaxel + gemcitabine, the treatment was associated with a higher incidence of grade ≥ 3 adverse events (86% vs. 68% for gemcitabine), indicating a need for careful consideration of safety alongside efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant nab-Paclitaxel + Gemcitabine in Resected Pancreatic Ductal Adenocarcinoma: Results From a Randomized, Open-Label, Phase III Trial. Tempero, MA., Pelzer, U., O'Reilly, EM., et al.[2023]

Nab-paclitaxel has recently been introduced as a first-line treatment for metastatic pancreatic ductal adenocarcinoma (PDAC), showing promising improvements in patient outcomes after years of stagnation in treatment options.

The review highlights the unique mechanism of action of nab-paclitaxel, particularly its interaction with albumin and SPARC, which may enhance its efficacy in targeting cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nab-paclitaxel for metastatic pancreatic cancer: clinical outcomes and potential mechanisms of action. Al-Batran, SE., Geissler, M., Seufferlein, T., et al.[2015]

In a phase II trial involving 30 patients with untreated metastatic pancreatic adenocarcinoma, the combination of capecitabine and nab-paclitaxel demonstrated a promising objective response rate of 41.4% and a disease control rate of 76%.

The treatment was well tolerated, with most patients able to escalate the nab-paclitaxel dose after the first course, and the most common adverse events were manageable, including sensory neuropathy and neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of capecitabine plus nab-paclitaxel in patients with metastatic pancreatic adenocarcinoma. Scheithauer, W., Kornek, G., Prager, G., et al.[2022]

The recent phase III MPACT trial demonstrated that nab-paclitaxel, when added to gemcitabine, significantly improved survival rates in patients with metastatic pancreatic cancer, indicating its efficacy in a previously challenging area.

The success of nab-paclitaxel highlights the importance of innovative drug delivery technologies, such as albumin nanoparticle formulations, in enhancing the effectiveness of anticancer therapies while minimizing toxicities associated with traditional formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The winning formulation: the development of paclitaxel in pancreatic cancer. Ma, WW., Hidalgo, M.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

The Association of Drug-Funding Reimbursement With Survival Outcomes and Use of New Systemic Therapies Among Patients With Advanced Pancreatic Cancer. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Durable response for ampullary and duodenal adenocarcinoma with a nab-paclitaxel plus gemcitabine ± cisplatin combination. [2022]

4. Greece pubmed.ncbi.nlm.nih.gov

Improvement of Treatment Outcomes for Metastatic Pancreatic Cancer: A Real-world Data Analysis. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Response and Survival Associated With First-line FOLFIRINOX vs Gemcitabine and nab-Paclitaxel Chemotherapy for Localized Pancreatic Ductal Adenocarcinoma. [2022]

6. New Zealand pubmed.ncbi.nlm.nih.gov

nab-Paclitaxel for the treatment of pancreatic cancer. [2023]

7. China pubmed.ncbi.nlm.nih.gov

Weekly albumin-bound paclitaxel/cisplatin versus gemcitabine/cisplatin as first-line therapy for patients with advanced non-small-cell lung cancer: A phase II open-label clinical study. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Adjuvant nab-Paclitaxel + Gemcitabine in Resected Pancreatic Ductal Adenocarcinoma: Results From a Randomized, Open-Label, Phase III Trial. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Nab-paclitaxel for metastatic pancreatic cancer: clinical outcomes and potential mechanisms of action. [2015]

10. China pubmed.ncbi.nlm.nih.gov

Phase II trial of capecitabine plus nab-paclitaxel in patients with metastatic pancreatic adenocarcinoma. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

The winning formulation: the development of paclitaxel in pancreatic cancer. [2022]