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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of combining two medications, olaparib (a PARP inhibitor) and pembrolizumab (an immunotherapy drug), following a low-dose multi-drug chemotherapy treatment for individuals with metastatic pancreatic cancer. It targets those who have not received prior treatment for this cancer. Individuals diagnosed with this type of pancreatic cancer and without previous treatment may be suitable candidates. The trial aims to evaluate how well this combination controls cancer and manages side effects. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using nab-paclitaxel and gemcitabine together can extend the lives of people with advanced pancreatic cancer. Most patients tolerate this treatment well, though some may experience side effects like low blood counts and nerve damage. Another study found that adding cisplatin to this combination was effective but led to more side effects, such as nausea and fatigue.

For ongoing treatment with pembrolizumab and olaparib, studies indicate this combination is generally safe. Patients with certain genetic traits responded positively, and the side effects were manageable. Common issues included fatigue and low red blood cell count, which are expected with these drugs.

Overall, while these combination treatments can cause side effects, studies have found them to be manageable. Patients should consult their doctor to determine if joining a trial is appropriate. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment for pancreatic cancer because it combines multi-agent chemotherapy with two innovative drugs: Olaparib and Pembrolizumab. Unlike traditional options that mainly focus on chemotherapy, Olaparib is a PARP inhibitor that targets cancer cell DNA repair mechanisms, potentially making the cancer more vulnerable to treatment. Pembrolizumab is an immunotherapy that helps the immune system recognize and attack cancer cells. This combination aims to enhance the effectiveness of chemotherapy and could offer a more comprehensive approach to tackling pancreatic cancer, giving researchers hope for improved patient outcomes.

What evidence suggests that this trial's treatments could be effective for pancreatic cancer?

Studies have shown that combining nab-paclitaxel and gemcitabine can extend the lives of patients with advanced pancreatic cancer. In this trial, participants will receive nab-paclitaxel, gemcitabine, cisplatin, irinotecan, and capecitabine. The trial will also continue treatment with pembrolizumab and olaparib. Research suggests that using olaparib and pembrolizumab together may shrink tumors in patients with certain genetic changes, such as BRCA1 or BRCA2 mutations. These findings offer hope that this treatment approach could be effective for pancreatic cancer. Overall, the evidence suggests potential benefits, especially for those with specific genetic profiles. ^{1 2 3 4 6}

Who Is on the Research Team?

Dung Le, MD

Principal Investigator

SKCCC Johns Hopkins Medical Institution

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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 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]

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]

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 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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03535727

A Study of Gemcitabine, Nab-paclitaxel, Capecitabine ... The purpose of this study is to evaluate the clinical activity of gemcitabine, nab-paclitaxel, capecitabine, cisplatin, and irinotecan (GAX-CI) in patients with ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11192994/

Phase II clinical trial of nab‐paclitaxel plus cisplatin plus ... NABPLAGEM has efficacy in advanced PDAC, demonstrating early disease control noted by improvement in patient symptoms, decrease in tumor volume and tumor ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1304369

Increased Survival in Pancreatic Cancer with nab-Paclitaxel In patients with metastatic pancreatic adenocarcinoma, nab-paclitaxel plus gemcitabine significantly improved overall survival, progression-free survival, and ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10461640/

First-line Treatment for Metastatic Pancreatic Cancer Despite advances in systemic therapy for the treatment of pancreatic ductal adenocarcinoma (PDAC), 5-year overall survival (OS) remains 11% for ...

5. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2752374

Response Rate Following Albumin-Bound Paclitaxel Plus ... Meaning Adding cisplatin to nab-paclitaxel and gemcitabine in this pilot study was associated with substantially increased clinical activity; ...

6. evidence.nejm.org evidence.nejm.org/doi/full/10.1056/EVIDoa2300144

Nab-Paclitaxel plus Gemcitabine and FOLFOX in Metastatic ... Sequential nab-P/Gem-mFOLFOX showed a significantly higher 12-month survival when compared with the standard nab-P/Gem treatment; this came with greater ...