Chemotherapy + Veliparib for Pancreatic Cancer

Not currently recruiting at 931 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Irinotecan, PARP inhibitors

Disqualifiers: Brain metastases, Seizures, Heart failure, 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

Duration: Varies, up to disease progression or unacceptable toxicity

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of chemotherapy drugs with veliparib to determine if it is more effective than chemotherapy alone for treating pancreatic cancer that has returned after treatment. The goal is to discover if adding veliparib, which may block enzymes that aid tumor cell growth, improves patient outcomes. Participants should have metastatic pancreatic cancer that has recurred after one treatment and should not have received irinotecan-based chemotherapy or certain other drugs previously. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, you must not have received prior irinotecan-based chemotherapy or PARP inhibitor therapy. 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?

A previous study found that combining veliparib with FOLFIRI did not present any unexpected safety issues for patients with pancreatic cancer, indicating no surprising or severe side effects. Veliparib, when used with treatments like gemcitabine and radiation, was generally well-tolerated, meaning most patients managed it without serious problems.

Research has shown that side effects are common with fluorouracil. About 70.8% of patients experienced some side effects, with around 27.2% facing serious ones, such as a drop in white blood cells (neutropenia). However, these effects are often manageable.

Irinotecan hydrochloride has been associated with serious outcomes, including hospitalizations and, in some cases, deaths. Despite this, when combined with other drugs, it has demonstrated an acceptable safety profile, meaning the benefits can outweigh the risks for many patients.

Overall, these treatments have been well-studied, showing that while side effects exist, they are often predictable and manageable. This trial aims to determine if adding veliparib can enhance treatment results without significantly increasing risks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination treatment involving veliparib for pancreatic cancer because it offers a new approach by incorporating a PARP inhibitor. Unlike the standard of care, which typically includes chemotherapy regimens like FOLFIRI, this treatment adds veliparib, which targets cancer cells' DNA repair mechanisms, potentially enhancing the effects of chemotherapy. This dual action could lead to more effective cancer cell destruction and improved outcomes for patients. Additionally, the innovative use of veliparib could provide benefits for individuals who have limited options with traditional treatments alone.

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

Research shows that veliparib, one of the treatments in this trial, may help treat pancreatic cancer when combined with other treatments. In one study, patients with advanced pancreatic cancer who took veliparib lived slightly longer. Some patients had their disease remain stable for 14% of the time, with a few experiencing benefits for up to 25 months. Veliparib blocks certain enzymes that help cancer cells grow. In this trial, one group of participants will receive a chemotherapy mix called FOLFIRI, which stops tumors by killing or stopping cancer cells from dividing. Another group will receive FOLFIRI combined with veliparib. The trial aims to determine if adding veliparib to FOLFIRI increases its effectiveness against recurrent pancreatic cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Elena G Chiorean

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

This trial is for patients with metastatic pancreatic cancer who have had one prior chemotherapy regimen but not irinotecan-based therapy or PARP inhibitors. They must have measurable disease, no history of brain metastases or seizures, and be in good physical condition (Zubrod performance status of 0-1). Participants need to have recovered from previous treatments' side effects and cannot have significant medical conditions like uncontrolled heart failure.

Inclusion Criteria

I have had only one treatment for my cancer since it spread.

Your blood levels of certain substances must be tested within 14 days before joining the study.

Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive either veliparib and modified FOLFIRI or FOLFIRI alone, with courses repeating every 14 days

Varies, up to disease progression or unacceptable toxicity

Bi-weekly visits for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Fluorouracil
• Irinotecan Hydrochloride
• Laboratory Biomarker Analysis
• Veliparib

Trial Overview The study compares modified FOLFIRI (irinotecan hydrochloride, leucovorin calcium, fluorouracil) plus Veliparib against standard FOLFIRI alone as a second-line treatment for metastatic pancreatic cancer. The goal is to see if adding Veliparib improves outcomes by blocking enzymes that help tumor cells grow.

How Is the Trial Designed?

Group I: Arm I (veliparib and mFOLFIRI) Experimental Treatment 5 Interventions

Patients receive veliparib PO BID every 12 hours on days 1-7, irinotecan hydrochloride IV over 90-120 minutes on day 3, leucovorin calcium IV over 90-120 minutes on day 3, and fluorouracil IV over 46 hours on days 3-5.

Group II: Arm II (FOLFIRI) Active Control 4 Interventions

Patients receive irinotecan hydrochloride IV over 90-120 minutes on day 1, leucovorin calcium IV over 90-120 minutes on day 1, and fluorouracil IV bolus over 15 minutes on days 1 and then over 46 hours on days 1-3.

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

Approved in United States as 5-Fluorouracil for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer
• Skin cancer

Approved in European Union as 5-Fluorouracil for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer

Approved in Canada as 5-Fluorouracil for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer

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

In a study of 493 patients with resected pancreatic cancer, the modified FOLFIRINOX regimen resulted in significantly longer disease-free survival (21.6 months) and overall survival (54.4 months) compared to gemcitabine (12.8 months and 35.0 months, respectively).

While modified FOLFIRINOX showed better efficacy, it also had a higher incidence of severe adverse events (75.9% vs. 52.9% for gemcitabine), indicating a trade-off between effectiveness and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer. Conroy, T., Hammel, P., Hebbar, M., et al.[2023]

The combination of irinotecan, epirubicin, and capecitabine has shown an acceptable toxicity profile in an open-label phase I study involving patients with metastatic adenocarcinomas, indicating it may be a safe treatment option.

The study is still ongoing, as the dose-limiting toxicity has not yet been reached, and further investigations will determine the optimal sequencing of the regimen to enhance clinical efficacy in treating upper gastrointestinal malignancies and breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan, epirubicin, and capecitabine in metastatic adenocarcinomas: preliminary results of a phase I study. Becerra, CR.[2018]

The modified FOLFIRINOX (mFOLFIRINOX) regimen showed a tolerable safety profile with lower hematological toxicity compared to the full-dose FOLFIRINOX, while still maintaining comparable efficacy in treating advanced pancreatic ductal adenocarcinoma (PDAC).

In a study of 18 patients, 80% achieved at least stable disease, with a median overall survival of 9.3 months and progression-free survival of 7.2 months, indicating that mFOLFIRINOX can be an effective treatment option for fit patients with advanced PDAC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Modified FOLFIRINOX for Advanced Pancreatic Adenocarcinoma: A UK Single-Centre Experience. Ghorani, E., Wong, HH., Hewitt, C., et al.[2023]

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 study involving 19 patients with unresectable pancreatic adenocarcinomas, the combination of cisplatin, 5-fluorouracil, and leucovorin resulted in a modest response rate, with one complete response and two partial responses (15.8%).

Although the treatment was associated with reversible and tolerable adverse effects, the overall limited efficacy means it cannot be recommended as a standard therapy for pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cisplatin, 5-Fluorouracil, and leucovorin in the therapy of adenocarcinomas of the pancreas. Jones, D., Sugarman, S., Markowitz, A., et al.[2019]

Modified FOLFIRINOX, which eliminates bolus 5-FU, shows an improved safety profile with low rates of severe side effects, such as only 3% experiencing grade 4 neutropenia, while maintaining efficacy in treating pancreatic cancer.

In patients with nonmetastatic pancreatic cancer, modified FOLFIRINOX resulted in a median overall survival of 17.8 months and a median progression-free survival of 13.7 months, indicating promising activity in this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modified FOLFIRINOX regimen with improved safety and maintained efficacy in pancreatic adenocarcinoma. Mahaseth, H., Brutcher, E., Kauh, J., et al.[2022]

In a phase II study involving 45 patients with unresectable or metastatic pancreatic cancer, the combination of irinotecan and gemcitabine showed promising efficacy, with a 20% overall response rate and a median survival of 5.7 months.

The treatment was well tolerated, with severe toxicities being rare, primarily consisting of low rates of grade 4 neutropenia and vomiting, indicating a favorable safety profile for this chemotherapy regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan plus gemcitabine induces both radiographic and CA 19-9 tumor marker responses in patients with previously untreated advanced pancreatic cancer. Rocha Lima, CM., Savarese, D., Bruckner, H., et al.[2022]

Irinotecan hydrochloride, approved in 1996 for second-line treatment of metastatic colorectal cancer, is generally well tolerated and can be safely administered on an outpatient basis, demonstrating clinically relevant activity against the disease.

Both irinotecan and gemcitabine, which will be discussed in a subsequent article, have manageable side effects that can be addressed with proper monitoring and dose adjustments, highlighting the importance of oncology nurses in patient education and symptom management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New agents in gastrointestinal malignancies: Part 1: Irinotecan in clinical practice. Stucky-Marshall, L.[2019]

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/34580114/

Randomized Phase II Study of PARP Inhibitor ABT ... - PubMed Median overall survival (OS) was 5.4 versus 6.5 months (HR, 1.23; P = 0.28), and median progression-free survival (PFS) was 2.1 versus 2.9 ...

3. aacrjournals.org aacrjournals.org/clincancerres/article/26/19/5092/82801/A-Phase-I-II-Study-of-Veliparib-ABT-888-in

A Phase I/II Study of Veliparib (ABT-888) in Combination with ... The combination was safe and effective for patients with metastatic pancreatic cancer ... Increased survival in pancreatic cancer with nab-paclitaxel plus ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2352396418306376

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

5. 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.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4229533/

Recent studies of 5-fluorouracil resistance in pancreatic ... The annual death rate for pancreatic cancer patients has remained stable over the past 10 years, and approximately 4% of patients survive for 5 years after ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.3_suppl.390

Real-world safety data and differentiation of second-line ... This study examined the proportion of patients (pts) with mPDAC treated with 5-FU-based regimens in the 2L setting who experienced AEs during treatment.

8. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-020-07110-x

Meta-analysis examining overall survival in patients with ... Meta-analysis examining overall survival in patients with pancreatic cancer treated with second-line 5-fluorouracil and oxaliplatin-based ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11871866/

Outcomes of Liposomal Irinotecan With 5‐FU and ... In this study, the median overall survival (OS) was significantly longer in the liposomal irinotecan plus 5-FU/LV group compared to the 5-FU/LV ...

10. asco.org asco.org/abstracts-presentations/ABSTRACT322037

Efficacy and safety of 5-fluorouracil (5-FU) / levofolinate ... Adverse events (AEs) were observed in 70.8% pts. Grade 3 or higher AEs occurred in 27.2% pts [neutropenia in 26 (25.2%) pts, febrile neutropenia in 4 (3.9%) pts ...