Gemcitabine + Cisplatin +/- Veliparib for Pancreatic Cancer

Not currently recruiting at 13 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding veliparib, a PARP inhibitor, to the standard chemotherapy drugs gemcitabine and cisplatin improves treatment for metastatic pancreatic cancer. Veliparib may inhibit cancer cell growth by blocking specific enzymes they require. The trial will compare three groups: one receiving all three drugs, one with only gemcitabine and cisplatin, and another with only veliparib. Individuals with pancreatic cancer who have a confirmed BRCA1, BRCA2, or PALB2 mutation and have not undergone extensive prior treatment may be suitable candidates. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research has shown that the combination of veliparib, gemcitabine, and cisplatin has been studied before. In earlier studies, this combination effectively controlled the disease, with patients responding positively to the treatment.

When used alone, veliparib was generally well tolerated, as studies found. Patients did not experience severe side effects, and some continued treatment for several months without cancer progression.

Gemcitabine and cisplatin, common chemotherapy drugs, have been used in many treatments and are usually well tolerated. Any side effects are typically known and manageable.

Overall, the safety information appears promising. However, as with any treatment, there may be risks. Participants should discuss potential side effects and benefits with their doctors. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for pancreatic cancer because they combine well-established chemotherapy agents, gemcitabine and cisplatin, with veliparib, a PARP inhibitor that targets cancer cells' DNA repair mechanisms. Unlike standard treatments that primarily focus on halting cell division, veliparib exploits the cancer cells' weaknesses by preventing them from repairing damaged DNA, potentially leading to more effective tumor destruction. This combination approach aims to enhance the efficacy of current therapies and offers new hope for patients by potentially improving outcomes in a notoriously hard-to-treat cancer.

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

Research has shown that using gemcitabine and cisplatin together effectively treats advanced pancreatic cancer, particularly in patients with genetic changes like BRCA1. Studies have found that this treatment can halt cancer progression for about 6.8 months and extend life to approximately 14 months. In this trial, one group of participants will receive gemcitabine and cisplatin alone, while another group will receive these drugs combined with veliparib, a drug that blocks enzymes involved in DNA repair and has shown promise in some early trials. However, another study found that adding veliparib did not significantly improve outcomes compared to using just gemcitabine and cisplatin. A separate group in this trial will receive veliparib alone, which has shown some effectiveness in small groups, though the response was modest, especially in individuals without BRCA mutations. ^{1 2 6 7 8}

Who Is on the Research Team?

Eileen M O'Reilly

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8639715/

Randomized Phase II Study of PARP Inhibitor ABT-888 ... Response and stable disease rates among 14 patients with refractory pancreatic cancers without known BRCA1/2 mutations were 14% (n=2, lasting 10 and 25 months) ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31976786/

Randomized, Multicenter, Phase II Trial of Gemcitabine and ... Phase IB data from a trial that used cisplatin, gemcitabine, and veliparib treatment demonstrated a high response rate (RR), disease control ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.19.02931

Randomized, Multicenter, Phase II Trial of Gemcitabine ... Phase IB data from a trial that used cisplatin, gemcitabine, and veliparib treatment demonstrated a high response rate (RR), disease control ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01585805

Study Details | NCT01585805 | Gemcitabine Hydrochloride ... This randomized phase II trial studies how well veliparib together with gemcitabine hydrochloride and cisplatin works compared to gemcitabine hydrochloride ...

5. thelancet.com thelancet.com/article/S2352-3964(18)30637-6/fulltext

A phase 1 study of veliparib, a PARP-1/2 inhibitor, with ... Randomized studies have shown modest clinical improvements with non-biomarker selected chemotherapies.

6. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT01908478

Study Details | NCT01908478 | Veliparib in Combination ... Determine the safety and toxicity of the combination of veliparib with gemcitabine and radiation therapy in patients with locally advanced pancreatic cancer.

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0959804917314016

Phase II trial of veliparib in patients with previously treated ... Veliparib was well tolerated, but no confirmed response was observed although four (25%) patients remained on study with SD for ≥ 4 months. Additional ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6412162/

A phase 1 study of veliparib, a PARP-1/2 inhibitor, with ... Pancreatic cancer (PC) has the lowest 5 year survival ... pancreatic cancer patients treated with single agent veliparib showed no responses [25].