Clinical Trials /

Study of Nivolumab in Combination With Gemcitabine/Cisplatin or Ipilimumab for Patients With Advanced Unresectable Biliary Tract Cancer

NCT03101566

Description:

The purpose of this trial is to evaluate the effect of investigational drug nivolumab in combination with either gemcitabine/cisplatin chemotherapy, or in combination with another investigational agent ipilimumab in patients with advanced unresectable biliary tract cancer. Gemcitabine/cisplatin is the standard of care treatment for biliary tract cancer. Nivolumab and ipilimumab are types of immunotherapy. Immunotherapy works by encouraging the body's own immune system to attack the cancer cells. Nivolumab (Opdivo) is FDA approved for the treatment of several cancers including metastatic melanoma, advanced lung, kidney, head & neck and bladder cancer. The combination of nivolumab and ipilimumab (Yervoy) is FDA approved for metastatic melanoma.

Related Conditions:
  • Biliary Tract Carcinoma
  • Extrahepatic Bile Duct Adenocarcinoma
  • Gallbladder Adenocarcinoma
  • Intrahepatic Bile Duct Adenoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Nivolumab in Combination With Gemcitabine/Cisplatin or Ipilimumab for Patients With Advanced Unresectable Biliary Tract Cancer
  • Official Title: A Multi-Center Randomized Phase II Study of Nivolumab in Combination With Gemcitabine/Cisplatin or Ipilimumab as First Line Therapy for Patients With Advanced Unresectable Biliary Tract Cancer [CA209-9FC]

Clinical Trial IDs

  • ORG STUDY ID: UMCC 2017.026
  • SECONDARY ID: HUM00126271
  • NCT ID: NCT03101566

Conditions

  • Biliary Tract Neoplasms

Interventions

DrugSynonymsArms
GemcitabineGemcitabine + Cisplatin + Nivolumab
CisplatinGemcitabine + Cisplatin + Nivolumab
IpilimumabNivolumab + Ipilimumab
NivolumabGemcitabine + Cisplatin + Nivolumab

Purpose

The purpose of this trial is to evaluate the effect of investigational drug nivolumab in combination with either gemcitabine/cisplatin chemotherapy, or in combination with another investigational agent ipilimumab in patients with advanced unresectable biliary tract cancer. Gemcitabine/cisplatin is the standard of care treatment for biliary tract cancer. Nivolumab and ipilimumab are types of immunotherapy. Immunotherapy works by encouraging the body's own immune system to attack the cancer cells. Nivolumab (Opdivo) is FDA approved for the treatment of several cancers including metastatic melanoma, advanced lung, kidney, head & neck and bladder cancer. The combination of nivolumab and ipilimumab (Yervoy) is FDA approved for metastatic melanoma.

Trial Arms

NameTypeDescriptionInterventions
Gemcitabine + Cisplatin + NivolumabExperimentalDrug: Gemcitabine 1000 mg/m2 IV over 30 minutes on days 1,8 every 3 weeks Drug: Cisplatin 25 mg/m2 IV over 30 minutes on days 1,8 every 3 weeks Drug: Nivolumab 360 mg IV over 30 minutes on day 1 every 3 weeks If there is continued benefit after 6 months, then: Drug: Nivolumab 240 mg IV over 30 minutes on day 1 every 2 weeks
  • Gemcitabine
  • Cisplatin
  • Nivolumab
Nivolumab + IpilimumabExperimentalDrug: Ipilimumab 1 mg/kg over 30 minutes on day 1 every 6 weeks Drug: Nivolumab 240 mg IV over 30 minutes on day 1 every 2 weeks
  • Ipilimumab
  • 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.

          -  Patients may have received prior radiation, chemoembolization, radioembolization or
             other local ablative therapies or hepatic resection if completed ≥ 4 weeks prior to
             registration AND if patient has recovered to <= grade 1 toxicity.

          -  Patients must have radiographically measurable disease 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.

          -  Age≥18 years

          -  Child-Pugh score of A (prognosis in chronic liver disease and cirrhosis)

          -  ECOG (Eastern Cooperative Oncology Group) performance status of 0-1

          -  Ability to understand and willingness to sign IRB-approved informed consent

          -  Willing to provide archived tissue, if available, from a previous diagnostic biopsy

          -  Must be able to tolerate CT (computerized tomography) and/or MRI (magnetic resonance
             imaging) with contrast

          -  Adequate organ function obtained ≤ 2 weeks prior to registration

        Exclusion Criteria:

          -  Patients may not have received prior systemic treatment (chemotherapy or targeted
             therapy) for advanced BTC (biliary tract cancer). Prior adjuvant chemotherapy is
             permitted provided it was completed > 6 months from registration.

          -  Must not have a diagnosis of immunodeficiency, or receiving systemic steroid therapy,
             or any other form of immunosuppressive therapy within 7 days prior to trial
             treatment.

          -  No known Hepatitis B, Hepatitis C, or HIV seropositivity. Testing is not required in
             absence of clinical suspicion.

          -  No prior history of organ transplantation or brain metastasis.

          -  Must not have undergone a major surgical procedure < 4 weeks prior to registration.

          -  Must not have an 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.

          -  Must have no ongoing active, uncontrolled infections

          -  Must not have received a live vaccine within 30 days of planned start of the study
             therapy.

          -  Must not 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.

          -  Women must not be pregnant or breastfeeding since nab-paclitaxel and/or gemcitabine
             may harm the fetus or child.

          -  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 5 months (for women) and 7
             months (for men) following completion of study therapy.

          -  Participants with an active, known or suspected autoimmune disease. 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The percentage of patients alive and without progression at 6 months following the initiation of treatment
Time Frame:6 Months
Safety Issue:
Description:The primary endpoint is PFS (Progression Free Survival) at 6 months following the initiation of treatment. Progression will be defined clinically or on imaging as per immune related response evaluation criteria in solid tumors (irRECIST) definition.

Secondary Outcome Measures

Measure:The percentage of patients that respond to treatment
Time Frame:Patients will be followed until death, withdrawal from study, or until 2 years, whichever is earliest
Safety Issue:
Description:Overall response rate is defined as the sum of partial responses and complete responses. Partial and complete response will be defined as per irRECIST criteria.
Measure:Median progression free survival time
Time Frame:Patients will be followed until death, withdrawal from study, or until 2 years, whichever is earliest
Safety Issue:
Description:The median time patients are alive without progression following the initiation of treatment wherein progression will be defined clinically or on imaging as per irRECIST criteria.
Measure:Median overall survival time
Time Frame:Patients will be followed until death, withdrawal from study, or until 2 years, whichever is earliest
Safety Issue:
Description:The median overall survival time following the initiation of treatment.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Michigan Cancer Center

Last Updated

March 30, 2017