Clinical Trials /

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

NCT03639935

Description:

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.

Related Conditions:
  • Adenocarcinoma
  • Biliary Tract Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Rucaparib in Combination With Nivolumab in Patients With Advanced or Metastatic Biliary Tract Cancer Following Platinum Therapy
  • 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

Clinical Trial IDs

  • ORG STUDY ID: UMCC 2018.044
  • SECONDARY ID: HUM00142974
  • NCT ID: NCT03639935

Conditions

  • Biliary Tract Cancer

Interventions

DrugSynonymsArms
RucaparibRucaparib and Nivolumab
NivolumabRucaparib and Nivolumab

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Rucaparib and NivolumabExperimentalRucaparib 600 mg PO BID days 1-28 Nivolumab 240 mg IV days 1 and 15
  • Rucaparib
  • Nivolumab

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Proportion of patients alive and without radiological or clinical progression at 4 months
Time Frame:4 months
Safety Issue:
Description: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

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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Michigan Rogel Cancer Center

Trial Keywords

  • Metastatic
  • Platinum
  • Rucaparib
  • Nivolumab
  • PARP Inhibitor
  • Anti-PD-1 Antibody

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