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Rucaparib in Combination With Nivolumab in Patients With Advanced or Metastatic Biliary Tract Cancer Following Platinum Therapy

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ClinicalTrials.gov Identifier: NCT03639935
Recruitment Status : Recruiting
First Posted : August 21, 2018
Last Update Posted : April 12, 2019
Sponsor:
Collaborators:
Dana-Farber Cancer Institute
Vanderbilt University Medical Center
Information provided by (Responsible Party):
University of Michigan Rogel Cancer Center

Brief Summary:
Investigators hypothesize that following first-line platinum based chemotherapy, rucaparib in combination with nivolumab, will improve progression-free survival and overall survival in BTC patients.

Condition or disease Intervention/treatment Phase
Biliary Tract Cancer Drug: Rucaparib Drug: Nivolumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 35 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Multi-Center Study of PARP Inhibitor Rucaparib in Combination With Anti-PD-1 Antibody Nivolumab in Patients With Advanced or Metastatic Biliary Tract Cancer Following Platinum Therapy
Actual Study Start Date : March 28, 2019
Estimated Primary Completion Date : January 2022
Estimated Study Completion Date : January 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Rucaparib and Nivolumab
Rucaparib 600 mg PO BID days 1-28 Nivolumab 240 mg IV days 1 and 15
Drug: Rucaparib
Rucaparib 600 mg PO BID days 1-28

Drug: Nivolumab
Nivolumab 240 mg IV days 1 and 15




Primary Outcome Measures :
  1. Proportion of patients alive and without radiological or clinical progression at 4 months [ Time Frame: 4 months ]

    Progressive disease is defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions (with a minimum absolute increase of 5 mm), taking as reference the smallest sum LD recorded since the treatment started, or the appearance of one or more new lesions.

    A clinical decision of progression by the site investigator will be based on the subject's overall clinical condition, including performance status, clinical symptoms, and laboratory data.



Secondary Outcome Measures :
  1. The proportion of patients that respond to treatment [ Time Frame: Up to two years post treatment start ]

    The proportion of patients that display a partial response (PR) or complete response (CR) to treatment.

    Partial response is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. There can be no appearance of new lesions.

    Complete response is defined as the disappearance of all target lesions, determined by two separate observations conducted not less than 4 weeks apart. There can be no appearance of new lesions.


  2. Progression free survival (PFS) time as measured from treatment start [ Time Frame: Up to two years post treatment discontinuation ]
    Progressive disease is defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions (with a minimum absolute increase of 5 mm), taking as reference the smallest sum LD recorded since the treatment started, or the appearance of one or more new lesions.

  3. Progression free survival (PFS) time as measured from start of 1st line platinum therapy [ Time Frame: Up to two years post treatment discontinuation ]
    Progressive disease is defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions (with a minimum absolute increase of 5 mm), taking as reference the smallest sum LD recorded since the treatment started, or the appearance of one or more new lesions.

  4. Overall survival (OS) time as measured from treatment start [ Time Frame: Up to two years post treatment discontinuation ]
  5. Overall survival (OS) time as measured from start of 1st line platinum therapy [ Time Frame: Up to two years post treatment discontinuation ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • Patients must have a pathologically confirmed adenocarcinoma of the biliary tract (intra-hepatic, extra-hepatic (hilar, distal) or gall bladder) that is not eligible for curative resection, transplantation, or ablative therapies. Tumors of mixed histology are excluded.
  • Patients must have received 1st line platinum-based systemic chemotherapy for advanced BTC for 4-6 months without radiologic or clinical progression. Last systemic infusion of 1st line platinum-based therapy may not be more than 4 weeks from study informed consent. Prior peri-operative chemotherapy is permitted provided it was completed > 6 months from start of platinum-based therapy for advanced disease.
  • Prior surgical resection, radiation, chemoembolization, radioembolization or other local ablative therapies are permitted if completed > 4 weeks prior to enrollment AND if patient has recovered to < 1 grade 1 toxicity.
  • Patients must have measurable disease (as per RECISTv1.1) in at least one site not previously treated with radiation or liver directed therapy (including bland, chemo- or radio-embolization, or ablation) either within the liver or in a metastatic site unless the patient has had complete response to 1st line platinum-based therapy.
  • Age≥18 years
  • Child-Pugh score of A or B7 (Scoring system used to assess the prognosis of chronic liver disease, mainly cirrhosis)
  • ECOG performance status of 0-1 (Eastern Cooperative Oncology Group scoring system used to quantify general well-being and activities of daily life; scores range from 0 to 5 where 0 represents perfect health and 5 represents death.)
  • Ability to understand and willingness to sign IRB-approved informed consent
  • Available archived tissue (FFPE block or 20 unstained slides from prior core biopsy or surgery)
  • Must be able to tolerate CT and/or MRI with contrast
  • Adequate organ function obtained ≤ 2 weeks prior to registration

Exclusion Criteria

  • Diagnosis of immunodeficiency, or received systemic steroid therapy, or any other form of immunosuppressive therapy within 14 days prior to trial treatment. Short bursts of steroids of 5-7 days (for COPD exacerbation or other similar indication) are allowed.
  • Prior history of solid organ transplantation or brain metastasis (unless treated and stable)
  • Patients may not have undergone a major surgical procedure < 4 weeks prior to registration
  • Active second malignancy other than non-melanoma skin cancer or cervical carcinoma in situ. Patients with history of malignancy are eligible provided primary treatment of that cancer was completed > 1 year prior to registration and the patient is free of clinical or radiologic evidence of recurrent or progressive malignancy.
  • Ongoing active, uncontrolled infections (afebrile for > 48 hours off antibiotics)
  • Have received a live vaccine within 30 days of planned start of the study therapy
  • Have a psychiatric illness, other significant medical illness, or social situation which, in the investigator's opinion, would limit compliance or ability to comply with study requirements
  • Pregnant or breastfeeding since rucaparib and/or nivolumab may harm the fetus or child. All females of childbearing potential (not surgically sterilized and between menarche and 1-year post menopause) must have a blood test to rule out pregnancy within 2 weeks prior to registration.
  • Women of child-bearing potential and men must agree to use 2 methods of adequate contraception (hormonal plus barrier or 2 barrier forms) OR abstinence prior to study entry, for the duration of study participation, and for 6 months (for women) and 7 months (for men) following completion of study therapy
  • Participants with an active, known or suspected autoimmune disease which may affect vital organ function, or has/may require systemic immunosuppressive therapy for management. Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
  • Participants with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of start of study treatment. Inhaled or topical steroids, and adrenal replacement steroid doses >10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
  • Patients may not have previously received anti PD1/PDL1 antibodies or PARP inhibitor for treatment of this cancer.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03639935


Contacts
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Contact: Vaibhav Sahai, MBBS, MS 734-936-4991 vsahai@med.umich.edu

Locations
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United States, Michigan
Rogel Cancer Center Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Vaibhav Sahai, MBBS, MS    734-936-4991      
Principal Investigator: Vaibhav Sahai, MBBS, MS         
Sponsors and Collaborators
University of Michigan Rogel Cancer Center
Dana-Farber Cancer Institute
Vanderbilt University Medical Center
Investigators
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Principal Investigator: Vaibhav Sahai, MBBS, MS Rogel Cancer Center

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Responsible Party: University of Michigan Rogel Cancer Center
ClinicalTrials.gov Identifier: NCT03639935     History of Changes
Other Study ID Numbers: UMCC 2018.044
HUM00142974 ( Other Identifier: University of Michigan )
First Posted: August 21, 2018    Key Record Dates
Last Update Posted: April 12, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD that underlie the results published in peer reviewed research articles, after deidentification.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: Beginning 9 months and ending 36 months following article publication.
Access Criteria: Investigators whose proposed use of the data is for meta-analysis, and has been approved by an independent review committee identified for this purpose. Proposals should be directed to vsahai@umich.edu. To gain access, data requestors will need to sign a data access agreement.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Michigan Rogel Cancer Center:
Metastatic
Platinum
Rucaparib
Nivolumab
PARP Inhibitor
Anti-PD-1 Antibody
Additional relevant MeSH terms:
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Biliary Tract Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Biliary Tract Diseases
Digestive System Diseases
Nivolumab
Rucaparib
Poly(ADP-ribose) Polymerase Inhibitors
Antineoplastic Agents, Immunological
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action