Niraparib for Pancreatic Cancer

Recruiting at 2 trial locations

Overseen By James Clreary, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: PARP inhibitors, TKIs

Disqualifiers: Brain metastases, HIV, MDS, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

32 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on certain therapies like cytotoxic chemotherapy, radiotherapy, or investigational therapies, you may need to stop them at least 2 weeks before starting the trial. It's best to discuss your specific medications with the trial team.

How does the drug Niraparib differ from other treatments for pancreatic cancer?

Niraparib is unique because it is a PARP inhibitor, which means it works by blocking a protein that helps repair DNA damage in cancer cells, potentially making it effective for cancers with specific genetic mutations. This mechanism is different from other treatments like chemotherapy, which directly kill cancer cells or inhibit their growth. ^{1 2 3 4 5}

What is the purpose of this trial?

This research study is studying an investigational therapy as a possible treatment for pancreatic cancer. The drugs involved in this study are: -Niraparib

Research Team

James M. Cleary

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

This trial is for adults with advanced pancreatic cancer who've had at least one prior treatment. They must have measurable disease, be in good physical condition (ECOG 0 or 1), and have proper organ function. Women of childbearing potential must test negative for pregnancy and agree to contraception; men also need to commit to using birth control. Participants can't join if they've recently received certain therapies, have specific blood disorders, are immunocompromised, or have untreated brain metastases.

Inclusion Criteria

My cancer has specific genetic changes in BRCA1, BRCA2, PALB2, CHEK2, or ATM.

I agree to use birth control from the start of the study until 6 months after it ends.

Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

Participants must not be immunocompromised.

I have a stomach or intestine problem that could affect how I absorb medication.

I have not recently had chemotherapy, radiotherapy, immunotherapy, or experimental treatments.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive niraparib orally once daily

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Long-term follow-up

Participants are monitored for overall survival

2 years

Treatment Details

Interventions

• Niraparib

Trial Overview The study is testing Niraparib as a potential treatment for pancreatic cancer in patients who meet certain genetic criteria related to mutations in genes like BRCA1/2. It's an investigational therapy which means it hasn’t been approved yet for general use. Patients will take the oral medication and their response will be monitored over time.

Participant Groups

Group I: Niraparib Experimental Treatment 1 Intervention

* Niraparib will be administered orally once daily * Palliative radiation therapy to a small field \>1 week prior to Day 1 of study treatment

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

Approved in European Union as Zejula for:

• Maintenance treatment of adults with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) following completion of first-line platinum-based chemotherapy
• Maintenance treatment of adults with platinum-sensitive relapsed high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy

Approved in United States as Zejula for:

• Maintenance treatment of adults with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy
• Treatment of adults with advanced ovarian, fallopian tube, or primary peritoneal cancer treated with three or more prior chemotherapy regimens and whose cancer is associated with homologous recombination deficiency (HRD)-positive status

Approved in Canada as Zejula for:

• Maintenance treatment of adults with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Tesaro, Inc.

Industry Sponsor

Trials

57

Recruited

10,600+

Findings from Research

In a phase II trial involving 67 patients with advanced pancreatic cancer who had previously failed gemcitabine therapy, vatalanib demonstrated a 6-month survival rate of 29%, indicating its potential efficacy as a second-line treatment.

Vatalanib was generally well tolerated, with common side effects including hypertension and fatigue, suggesting it may be a viable option for patients who have limited treatment alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of vatalanib in patients with advanced or metastatic pancreatic adenocarcinoma after first-line gemcitabine therapy (PCRT O4-001). Dragovich, T., Laheru, D., Dayyani, F., et al.[2022]

In a phase I trial involving 50 patients with advanced pancreatic cancer, the combination of nivolumab, nab-paclitaxel, and gemcitabine showed a manageable safety profile, with 48 patients experiencing grade 3/4 treatment-emergent adverse events, but only one dose-limiting toxicity reported.

The treatment resulted in a median overall survival of 9.9 months and an overall response rate of 18%, indicating limited efficacy, which led to the conclusion that further investigation of this combination is not supported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-label, Phase I Study of Nivolumab Combined with nab-Paclitaxel Plus Gemcitabine in Advanced Pancreatic Cancer. Wainberg, ZA., Hochster, HS., Kim, EJ., et al.[2022]

In a phase II trial involving 17 patients with advanced pancreatic cancer, the combination of sorafenib and gemcitabine showed no objective responses, with only 18% of patients achieving stable disease.

The treatment resulted in a median overall survival of 4.0 months and was associated with significant toxicities, including thrombosis in 18% of patients, indicating that this combination is not effective for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine plus sorafenib in patients with advanced pancreatic cancer: a phase II trial of the University of Chicago Phase II Consortium. Kindler, HL., Wroblewski, K., Wallace, JA., et al.[2022]

The combination of gemcitabine, capecitabine, bevacizumab, and erlotinib showed promising efficacy in treating advanced pancreatic cancer, with 10 partial responses observed among 20 patients and median overall survival of 12.5 months.

The maximum-tolerated dose of capecitabine was determined to be 1,660 mg/m², with a recommended dose of 1,440 mg/m² for further studies, while the treatment was generally well-tolerated with manageable side effects like diarrhea and skin rash.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose finding and early efficacy study of gemcitabine plus capecitabine in combination with bevacizumab plus erlotinib in advanced pancreatic cancer. Starling, N., Watkins, D., Cunningham, D., et al.[2022]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Phase II trial of vatalanib in patients with advanced or metastatic pancreatic adenocarcinoma after first-line gemcitabine therapy (PCRT O4-001). [2022]

2. England pubmed.ncbi.nlm.nih.gov

Randomised phase II trial of gemcitabine and nab-paclitaxel with necuparanib or placebo in untreated metastatic pancreas ductal adenocarcinoma. [2022]

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

Open-label, Phase I Study of Nivolumab Combined with nab-Paclitaxel Plus Gemcitabine in Advanced Pancreatic Cancer. [2022]

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

Gemcitabine plus sorafenib in patients with advanced pancreatic cancer: a phase II trial of the University of Chicago Phase II Consortium. [2022]

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

Dose finding and early efficacy study of gemcitabine plus capecitabine in combination with bevacizumab plus erlotinib in advanced pancreatic cancer. [2022]