Niraparib + Ipilimumab or Nivolumab in Progression Free Pancreatic Adenocarcinoma After Platinum-Based Chemotherapy

• Status: Recruiting
• Trial end date: 2024-06-01
• Target enrollment: 0
• Participant gender: All

Summary

The main purpose of this study is to look at the effectiveness, safety, and anti-tumor activity (preventing growth of the tumor) of the drugs Niraparib with either Ipilimumab or Nivolumab on patients and their pancreatic cancer.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Pennsylvania
• Collaborators: Bristol-Myers Squibb; Tesaro, Inc.
• Treatments: Antibodies, Monoclonal; Ipilimumab; Niraparib; Nivolumab

Criteria

Inclusion Criteria:

1. Histologically or cytologically confirmed diagnosis of pancreatic adenocarcinoma with locally advanced or metastatic disease

2. ≥18 years of age

3. Expected life expectancy of at least 12 weeks

4. Patients must be able to understand the study procedures and agree to participate in the study by providing written informed consent

5. Patients must have received treatment with platinum-based (cisplatin, oxaliplatin or carboplatin) treatment for locally advanced or metastatic pancreatic cancer and have received a minimum of 16 weeks of therapy without evidence of disease progression based on the investigator's opinion. This does not have to be the patient's current treatment.

• This requires at least stable imaging and a stable or decreasing tumor marker as applicable and as determined by the investigator.

• If a patient has demonstrated a biochemical and imaging response to platinum therapy and has not progressed within 16 weeks of starting this therapy but had to discontinue platinum prior to 16 weeks for a legitimate medical reason (as determined by the investigator), the patient may still be considered for the trial

• Patients may have previously failed non-platinum containing therapy or may never have previously progressed on treatment

• Discontinuation of the platinum component of the regimen for chemotherapy-related toxicity is permissible provided the patient has previously received at least 16 weeks of platinum-based therapy without evidence of disease progression ≤8 weeks after treatment with the platinum agent

• Measurable disease is not a requirement for study entry

6. Patient agrees to peripheral blood samples during screening and at the end of treatment for cytogenetic analysis.

7. Adequate organ function confirmed ≤7 days prior to the first day of study therapy

Exclusion Criteria:

1. Prior treatment with a PARP inhibitor, ipilimumab, nivolumab or other cytotoxic T-lymphocyte-associated protein (CTLA-4), PD-1 or PD-L1 inhibitor.

2. Patients who have demonstrated resistance to platinum agents (e.g. oxaliplatin, cisplatin) are not eligible to participate in this study

3. Clinical evidence of uncontrolled malabsorption and/or any other gastrointestinal disorder or defect that would, in the opinion of the investigator, interfere with the absorption of niraparib

4. Acute infection requiring intravenous antibiotics, antiviral or antifungal agents during the 14 days prior to first dose of study therapy

5. Patients will be excluded if they have an active, known or suspected autoimmune disease, defined as: patients with a history of inflammatory bowel disease are excluded from this study, as are patients with a history of symptomatic autoimmune disease (eg rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematosus, autoimmune vasculitis eg Wegener's Granulomatosis); motor neuropathy considered of autoimmune origin (eg Guillain-Barre Syndrome).

NOTE: Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.

6. Has a history of interstitial lung disease or active, non-infectious pneumonitis

7. Has received a live vaccine within 4 weeks prior to the first dose of trial therapy (Note: seasonal influenza vaccines for injection are generally inactivated and are allowed; however intranasal influenza vaccines (eg. Flu-Mist) are live attenuated vaccines and are not allowed

8. For fertile patient (female able to become pregnant or male able to father a child), refusal to use effective contraception during the period of the trial and for 5 months after the last dose of study drug.

9. Received any systemic treatment for pancreatic cancer ≤14 days prior to first dose of therapy. Patients must not have had investigational therapy administered ≤ 4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is longer, prior to the first scheduled day of dosing in this study

10. Patients will be excluded if they have a condition requiring systemic treatment with either corticosteroids (>10mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses >10mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.

11. Patient has had any known Grade 3 or 4 anemia, neutropenia or thrombocytopenia due to prior chemotherapy that persisted > 4 weeks and was related to the most recent treatment.

12. Non-study related minor surgical procedure ≤5 days, or major surgical procedure ≤21 days, prior to the first dose of therapy; in all cases, patients must be sufficiently recovered and stable before treatment administration.

13. Active drug or alcohol use or dependence that would interfere with study compliance.

14. Presence of any other condition that may increase the risk associated with study participation or may interfere with the interpretation of study results, and, in the opinion of the investigator, would make the patient inappropriate for entry into the study.

15. Patient must not have any known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)

16. Patients must not be simultaneously enrolled in any therapeutic clinical trial

17. Patients must not have had radiotherapy within 4 weeks of the first dose of study treatment

18. Patients must not have a known hypersensitivity to the components of niraparib or the excipients

19. Patients must not have received a transfusion (platelets or red blood cells) ≤ 4 weeks of the first dose of study treatment

20. Patients must not be undergoing treatment for an active cancer at the time of randomization. Exceptions include: local therapies for skin cancers and hormonal therapies for breast or prostate cancer.

21. Patients may not have a history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).

22. Patients must not have known, symptomatic brain or leptomeningeal metastases