Gemcitabine + Cisplatin +/- Veliparib for Pancreatic Cancer

Recruiting at 11 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: PARP inhibitors

Disqualifiers: Active infection, Seizures, CNS metastasis, 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: 3

88 Participants Needed

Trial Summary

What is the purpose of this trial?

This randomized phase II trial studies how well veliparib together with gemcitabine hydrochloride and cisplatin works compared to gemcitabine hydrochloride and cisplatin alone in treating patients with pancreatic cancer that has spread from where it started to nearby tissue or lymph nodes (locally advanced) or spread from the primary site (place where it started) to other places in the body (metastatic). Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine hydrochloride and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving veliparib together with gemcitabine hydrochloride and cisplatin is an effective treatment for pancreatic cancer.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, you cannot participate if you are receiving other investigational agents or have had chemotherapy or radiotherapy within 3 weeks before entering the study.

What data supports the effectiveness of the drug combination Gemcitabine + Cisplatin +/- Veliparib for pancreatic cancer?

Studies have shown that combining gemcitabine with cisplatin can improve response rates and survival in patients with pancreatic cancer, with response rates ranging from 11.4% to 58% and median survival times of 7.4 to 10 months. However, these findings need confirmation in larger studies. ^{1 2 3 4 5}

Is the combination of Gemcitabine, Cisplatin, and Veliparib safe for humans?

The combination of Gemcitabine and Cisplatin has been tested in several studies and is generally safe, though it can cause myelosuppression (a decrease in bone marrow activity leading to fewer blood cells). Veliparib has been tested with these drugs in early trials, and while specific safety data for this combination is limited, the trials aim to determine safe dosage levels. ^{1 6 7 8 9}

What makes the drug combination of Gemcitabine, Cisplatin, and Veliparib unique for treating pancreatic cancer?

This drug combination is unique because it includes Veliparib, which is not commonly used in standard treatments for pancreatic cancer. Gemcitabine and Cisplatin are known to work well together, potentially improving response rates and survival, but Veliparib may offer additional benefits by targeting cancer cells in a different way, although its specific role in this combination is still being studied. ^{1 3 5 10 11}

Research Team

Eileen M O'Reilly

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for adults with advanced or metastatic pancreatic cancer. Eligible participants include those who have not had prior treatment for advanced disease, or if they've had adjuvant therapy, it must be at least 6 months since completion. Participants need a confirmed BRCA1/2 or PALB2 mutation and should not be pregnant, as the drugs could harm the fetus. They must also agree to use contraception.

Inclusion Criteria

I have advanced pancreatic cancer with a confirmed BRCA or PALB2 mutation.

Your platelet count is at least 100,000 per microliter within 14 days before taking ABT-888.

Your total bilirubin levels should be within a certain range, as determined by the hospital, before starting the treatment.

Exclusion Criteria

I have not had PARP inhibitor therapy and have had up to two prior cancer treatments.

Patients may not be receiving any other investigational agents

I do not have any serious illnesses or social situations that would stop me from following the study's requirements.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part I

Patients receive veliparib, gemcitabine hydrochloride, and cisplatin in a randomized study to evaluate response rates and optimize dosing.

21-day cycles, repeated

Multiple visits for drug administration and monitoring

Treatment Part II

Patients receive single-agent veliparib in previously treated pancreas adenocarcinoma.

28-day cycles, repeated

Multiple visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

Up to 5 years

Follow-up visits every 3 months

Treatment Details

Interventions

• Cisplatin
• Gemcitabine Hydrochloride
• Veliparib

Trial Overview The study tests whether adding Veliparib to standard chemotherapy (Gemcitabine Hydrochloride and Cisplatin) improves outcomes in patients with pancreatic cancer that has spread. Patients are randomly assigned to receive either the combination of all three drugs or just the chemotherapy alone.

Participant Groups

Group I: Arm C (veliparib) Experimental Treatment 4 Interventions

Patients receive veliparib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial.

Group II: Arm A (veliparib, gemcitabine hydrochloride, cisplatin) Experimental Treatment 8 Interventions

Patients receive veliparib PO BID on days 1-12 or 1-21 of each cycle. Patients also receive gemcitabine hydrochloride IV over 30 minutes and cisplatin IV over 30 minutes on days 3 and 10 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.

Group III: Arm B (gemcitabine hydrochloride, cisplatin) Active Control 7 Interventions

Patients receive gemcitabine hydrochloride IV and cisplatin IV as patients in arm A. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.

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

Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a phase 2 study involving 36 patients with advanced pancreatic cancer, the combination of cisplatin and gemcitabine showed promising activity, with 62.8% of patients achieving stable disease or better, and a median survival of 9.5 months.

While significant hematological toxicities were observed, they were mostly asymptomatic, and the treatment regimen demonstrated potential for improving survival, warranting further investigation in a larger randomized controlled trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of weekly cisplatin and gemcitabine in patients with advanced pancreatic cancer: is this a strategy still worth pursuing? Clayton, AJ., Mansoor, AW., Jones, ET., et al.[2022]

Gemcitabine has changed the perception of pancreatic cancer treatment, showing good tolerability and low side effects, making it a viable option for combination therapies with drugs like cisplatin and 5-fluorouracil.

Combination regimens with gemcitabine and cisplatin have shown response rates between 11.4% and 58% and median survival times of 7.4 to 10 months, while gemcitabine with 5-FU has lower response rates and survival times, indicating the need for further optimization of treatment combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine-based combination treatment of pancreatic cancer. Heinemann, V.[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]

Gemcitabine is now considered a standard treatment for advanced pancreatic cancer due to its effectiveness and favorable side-effect profile.

While combinations of gemcitabine with other antitumor drugs and biological agents have shown promise in phase II trials, none have yet been established as an evidence-based standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Present and future treatment of pancreatic cancer. Heinemann, V.[2022]

In a phase II trial involving 50 patients with advanced pancreatic ductal adenocarcinoma (PDAC) and gBRCA/PALB2 mutations, the combination of cisplatin and gemcitabine showed a high response rate of 74.1% and a disease control rate of 100% when combined with veliparib, compared to a 65.2% response rate and 78.3% disease control rate without veliparib.

Despite the addition of veliparib, there was no significant improvement in response rates or overall survival compared to cisplatin and gemcitabine alone, establishing the latter as a standard treatment for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, Multicenter, Phase II Trial of Gemcitabine and Cisplatin With or Without Veliparib in Patients With Pancreas Adenocarcinoma and a Germline BRCA/PALB2 Mutation. O'Reilly, EM., Lee, JW., Zalupski, M., et al.[2022]

In a phase II study involving 45 patients with advanced pancreatic cancer, the combination of gemcitabine and cisplatin resulted in a low overall response rate of only 9%, with one complete and four partial responses observed.

Despite some patients experiencing stable disease (46%) and a median survival of 5.6 months, the study concluded that this chemotherapy regimen did not provide a significant advantage in efficacy, and side effects were primarily hematological, with notable toxicities requiring dose reductions in 31% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weekly gemcitabine and cisplatin chemotherapy: a well-tolerated but ineffective chemotherapeutic regimen in advanced pancreatic cancer patients. A report from the Italian Group for the Study of Digestive Tract Cancer (GISCAD). Cascinu, S., Labianca, R., Catalano, V., et al.[2022]

References

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

Gemcitabine and platinum combinations in pancreatic cancer. [2022]

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

A phase II study of weekly cisplatin and gemcitabine in patients with advanced pancreatic cancer: is this a strategy still worth pursuing? [2022]

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

Gemcitabine-based combination treatment of pancreatic cancer. [2022]

4. 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]

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

Present and future treatment of pancreatic cancer. [2022]

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

Phase 1 trial evaluating cisplatin, gemcitabine, and veliparib in 2 patient cohorts: Germline BRCA mutation carriers and wild-type BRCA pancreatic ductal adenocarcinoma. [2023]

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

Randomized, Multicenter, Phase II Trial of Gemcitabine and Cisplatin With or Without Veliparib in Patients With Pancreas Adenocarcinoma and a Germline BRCA/PALB2 Mutation. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Gemcitabine and cisplatin in the treatment of advanced or metastatic pancreatic cancer. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Weekly gemcitabine and cisplatin chemotherapy: a well-tolerated but ineffective chemotherapeutic regimen in advanced pancreatic cancer patients. A report from the Italian Group for the Study of Digestive Tract Cancer (GISCAD). [2022]

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

Efficacy and Tolerability of Second-line Nab-paclitaxel and Gemcitabine After Failure of First-line FOLFIRINOX for Advanced Pancreas Cancer: A Single-institution Experience. [2022]

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

Phase II study of gemcitabine and cisplatin in the treatment of patients with advanced pancreatic carcinoma. [2022]