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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Biliary Tract Cancer
• Intervention / Treatment: Drug: Rucaparib; Drug: Nivolumab

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Rogel Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 or urine 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients alive and without radiological or clinical progression at 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.	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of patients that respond to treatment	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.	Up to two years post treatment start
Progression free survival (PFS) time as measured from treatment start	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.	Up to two years post treatment discontinuation
Progression free survival (PFS) time as measured from start of 1st line platinum therapy	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.	Up to two years post treatment discontinuation
Overall survival (OS) time as measured from treatment start		Up to two years post treatment discontinuation
Overall survival (OS) time as measured from start of 1st line platinum therapy		Up to two years post treatment discontinuation

Collaborators and Investigators

• Sponsor: University of Michigan Rogel Cancer Center
• Collaborators: Dana-Farber Cancer Institute; Vanderbilt University Medical Center
• Investigators: Principal Investigator: Vaibhav Sahai, MBBS, MS, Rogel Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2019
• Primary Completion (Actual): February 7, 2023
• Study Completion (Estimated): February 1, 2025

Study Registration Dates

• First Submitted: August 17, 2018
• First Submitted That Met QC Criteria: August 17, 2018
• First Posted (Actual): August 21, 2018

Study Record Updates

• Last Update Posted (Actual): August 31, 2023
• Last Update Submitted That Met QC Criteria: August 30, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Nivolumab; PARP Inhibitor; Metastatic; Platinum; Rucaparib; Anti-PD-1 Antibody
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Biliary Tract Diseases; Biliary Tract Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Poly(ADP-ribose) Polymerase Inhibitors; Immune Checkpoint Inhibitors; Nivolumab; Rucaparib
• Other Study ID Numbers: UMCC 2018.044; HUM00142974 (Other Identifier: University of Michigan)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD that underlie the results published in peer reviewed research articles, after deidentification.
• IPD Sharing Time Frame: Beginning 9 months and ending 36 months following article publication.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No