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

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ClinicalTrials.gov Identifier: NCT03404960
Recruitment Status : Recruiting
First Posted : January 19, 2018
Last Update Posted : June 10, 2021
Sponsor:
Collaborators:
Bristol-Myers Squibb
Tesaro, Inc.
Information provided by (Responsible Party):
University of Pennsylvania

Tracking Information
First Submitted Date  ICMJE December 19, 2017
First Posted Date  ICMJE January 19, 2018
Last Update Posted Date June 10, 2021
Actual Study Start Date  ICMJE January 31, 2018
Estimated Primary Completion Date March 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 12, 2018)
Progression-free survival [ Time Frame: 6 months after initiation of study therapy ]
Progression-free survival at 6 months (PFS6) for both combinations according to RECIST v1.1, as assessed by the investigator
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 12, 2018)
  • Proportion of tumors with homologous recombination deficits (HRD), in patients with stability or response to platinum therapy [ Time Frame: Cycle 1 Day 1 through completion of study treatment (maximum 42 months) ]
    Identification of HRDs and allele specific LOH via whole exome sequencing
  • Objective response rate (ORR) in those with measurable disease [ Time Frame: From first restaging assessment through completion of study treatment (maximum 42 months) ]
    Measured by CT scans and other studies (MRI, X-ray, PET, and ultrasound)
  • Duration of response (DOR) [ Time Frame: From first restaging assessment until death, loss to follow-up, withdrawal of consent or until 5 years have passed, whichever occurs first ]
    Measured by CT scans and other studies (MRI, X-ray, PET, and ultrasound)
  • Overall survival (OS) [ Time Frame: Cycle 1 Day 1 until death, loss to follow-up, withdrawal of consent or until 5 years have passed, whichever occurs first ]
    start of treatment to death due to any cause or last patient contact alive
  • Safety and tolerability of this combination. Number of participants with treatment-related adverse events as assessed by CTCAE version 4.03 [ Time Frame: From the initiation of any study intervention through 100 days (nivolumab patients) or 90 days (all patients) after patient End of Treatment Visit ]
    Safety based upon standard laboratory and clinical adverse event monitoring
  • Correlation of HRDs with response to treatment with niraparib plus immune checkpoint blockade [ Time Frame: Cycle 1 Day 1 through completion of study treatment (maximum 42 months) ]
    Identification of HRDs and allele specific LOH via whole exome sequencing
  • Immune activation prior to treatment [ Time Frame: Prior to initiation of study therapy (maximum 36 months) ]
    Assessed using immune biomarkers, and RNAseq of PBMC
  • Immune activation prior during treatment [ Time Frame: Following receipt of study therapy and through study completion (maximum 42 months) ]
    Assessed using immune biomarkers, and RNAseq of PBMC
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Niraparib + Ipilimumab or Nivolumab in Progression Free Pancreatic Adenocarcinoma After Platinum-Based Chemotherapy
Official Title  ICMJE PARPVAX: Parpvax: A Phase 1b/2, Open Label Study of Niraparib Plus Either Ipilimumab or Nivolumab in Patients With Advanced Pancreatic Cancer Whose Disease Has Not Progressed on Platinum-based Therapy
Brief 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Pancreatic Adenocarcinoma
Intervention  ICMJE
  • Drug: Niraparib + Nivolumab
    Niraparib 200mg PO daily on days 1-21 of each 21 day cycle Nivolumab 240mg IV days 1 and 15 of odd-numbered cycles; day 8 of even numbered cycles
  • Drug: Niraparib + Ipilimumab
    Niraparib 200mg PO daily on days 1-21 of each 21 day cycle Ipilimumab 3mg/kg IV day 1 of each cycle, for the first 4 cycles only
Study Arms  ICMJE
  • Experimental: Arm A
    Niraparib + Nivolumab
    Intervention: Drug: Niraparib + Nivolumab
  • Experimental: Arm B
    Niraparib + Ipilimumab
    Intervention: Drug: Niraparib + Ipilimumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 12, 2018)
84
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2024
Estimated Primary Completion Date March 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Abranmson Cancent Center Clinical Trials Service 855-216-0098 PennCancerTrials@emergingmed.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03404960
Other Study ID Numbers  ICMJE 828516
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Pennsylvania
Study Sponsor  ICMJE University of Pennsylvania
Collaborators  ICMJE
  • Bristol-Myers Squibb
  • Tesaro, Inc.
Investigators  ICMJE Not Provided
PRS Account University of Pennsylvania
Verification Date June 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP