Chemotherapy + Veliparib for Pancreatic Cancer

Recruiting at 908 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

123 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug combination including Irinotecan and Veliparib for pancreatic cancer?

Research shows that Irinotecan, when combined with other drugs like gemcitabine, has shown promising results in treating pancreatic cancer, with some patients experiencing partial responses. Additionally, combination therapies involving Irinotecan have been effective in improving survival times in advanced pancreatic cancer. ^{1 2 3 4 5}

Is the combination of chemotherapy drugs including 5-FU and irinotecan safe for treating pancreatic cancer?

The combination of chemotherapy drugs like 5-FU and irinotecan has been used in treating pancreatic cancer and is generally considered safe with manageable side effects. These side effects can be controlled with proper monitoring and adjustments to the treatment if needed. ^{3 6 7 8 9}

How is the drug combination of Chemotherapy + Veliparib unique for treating pancreatic cancer?

The combination of chemotherapy drugs like 5-fluorouracil and irinotecan with Veliparib is unique because Veliparib is a PARP inhibitor, which may enhance the effectiveness of chemotherapy by preventing cancer cells from repairing themselves, potentially offering a novel approach compared to standard treatments like FOLFIRINOX or gemcitabine-based therapies. ^{9 10 11 12 13}

What is the purpose of this trial?

This randomized phase II trial studies how well modified irinotecan hydrochloride, leucovorin calcium, fluorouracil (FOLFIRI) and veliparib as a second line of therapy work compared to FOLFIRI in treating patients with pancreatic cancer that has come back after a period of improvement (metastatic). Drugs used in chemotherapy, such as irinotecan hydrochloride, leucovorin calcium, and fluorouracil, 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. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether modified FOLFIRI and veliparib as second line therapy is more effective than FOLFIRI alone in treating metastatic pancreatic cancer.

Research Team

Elena G Chiorean

Principal Investigator

SWOG Cancer Research Network

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. Greece pubmed.ncbi.nlm.nih.gov

Irinotecan(Campto R): efficacy as third/forth line therapy in advanced pancreatic cancer. [2018]

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

Irinotecan in the management of patients with pancreatic cancer. [2018]

3. United States 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. [2022]

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

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

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

Gemcitabine, Docetaxel, Capecitabine, Cisplatin, Irinotecan as First-line Treatment for Metastatic Pancreatic Cancer. [2023]

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

Modified FOLFIRINOX regimen with improved safety and maintained efficacy in pancreatic adenocarcinoma. [2022]

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

New agents in gastrointestinal malignancies: Part 1: Irinotecan in clinical practice. [2019]

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

Gemcitabine, oxaliplatin and weekly high-dose 5-FU as 24-h infusion in chemonaive patients with advanced or metastatic pancreatic adenocarcinoma: a multicenter phase II trial of the Arbeitsgemeinschaft Internistische Onkologie (AIO). [2022]

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

Safety and Efficacy of Modified FOLFIRINOX for Advanced Pancreatic Adenocarcinoma: A UK Single-Centre Experience. [2023]

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

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

11. England pubmed.ncbi.nlm.nih.gov

Phase II study of cisplatin and 120-hour continuous infusion of 5-fluorouracil in patients with advanced pancreatic adenocarcinoma. [2020]

12. Greece pubmed.ncbi.nlm.nih.gov

Cisplatin, 5-Fluorouracil, and leucovorin in the therapy of adenocarcinomas of the pancreas. [2019]

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

FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer. [2023]