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

NCT03101566 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: UMCC 2017.026HUM00126271HUM00130035
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Biliary Tract Neoplasms

Outcome Measures

Primary Outcomes (1)

• The Percentage of Patients Alive and Without Progression at 6 Months Following the Initiation of Treatment

  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.

  6 Months

Secondary Outcomes (3)

• Median Progression Free Survival Time

  Patients will be followed until death, withdrawal from study, or until 2 years, whichever is earliest

• Median Overall Survival Time

  Patients will be followed until death, withdrawal from study, or until 2 years, whichever is earliest

• Overall Response Rate (ORR)

  Up to two years

Study Arms (2)

Gemcitabine + Cisplatin + Nivolumab

EXPERIMENTAL

Drug: Gemcitabine 1000 mg/m2 IV on days 1,8 every 3 weeks Drug: Cisplatin 25 mg/m2 IV on days 1,8 every 3 weeks Drug: Nivolumab 360 mg IV on day 1 every 3 weeks If there is continued benefit after 6 months, then: Drug: Nivolumab 240 mg IV on day 1 every 2 weeks

Drug: Gemcitabine; Drug: Cisplatin; Drug: Nivolumab

Nivolumab + Ipilimumab

EXPERIMENTAL

Drug: Ipilimumab 1 mg/kg IV on day 1 every 6 weeks Drug: Nivolumab 240 mg IV on day 1 every 2 weeks

Drug: Ipilimumab; Drug: Nivolumab

Interventions

Gemcitabine DRUG

Gemcitabine 1000 mg/m2 IV

Gemcitabine + Cisplatin + Nivolumab

Cisplatin DRUG

Cisplatin 25 mg/m2 IV

Gemcitabine + Cisplatin + Nivolumab

Ipilimumab DRUG

Ipilimumab 1 mg/kg IV

Nivolumab + Ipilimumab

Nivolumab DRUG

Nivolumab 360 mg or 240 mg IV

Gemcitabine + Cisplatin + Nivolumab; Nivolumab + Ipilimumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 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. Extrahepatic palliative radiation is permitted if completed ≥ 2 weeks prior to enrollment 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.
• Must be ≥18 years of age
• Must have a Child-Pugh score of A (prognosis in chronic liver disease and cirrhosis)
• Must have an 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
• Must have adequate organ function obtained ≤ 2 weeks prior to registration

You may not qualify if:

• 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 have received systemic steroid therapy, or any other form of immunosuppressive therapy within 7 days prior to trial treatment.
• Must not have known Hepatitis B, Hepatitis C, or HIV seropositivity. Testing is not required in absence of clinical suspicion.
• Must not have 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 study drugs 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 which may affect vital organ function, or has/may require systemic immunosuppressive therapy for management are excluded. 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 7 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.

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead

Study Sites (7)

Emory University

Atlanta, Georgia, 30322, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

University of Washington

Seattle, Washington, 98109, United States

Location

University of Wisconsin

Madison, Wisconsin, 53705, United States

Location

Related Publications (1)

• Sahai V, Griffith KA, Beg MS, Shaib WL, Mahalingam D, Zhen DB, Deming DA, Zalupski MM. A randomized phase 2 trial of nivolumab, gemcitabine, and cisplatin or nivolumab and ipilimumab in previously untreated advanced biliary cancer: BilT-01. Cancer. 2022 Oct 1;128(19):3523-3530. doi: 10.1002/cncr.34394. Epub 2022 Jul 27.

  PMID: 35895381 DERIVED

MeSH Terms

Conditions

Biliary Tract Neoplasms

Interventions

Gemcitabine; Cisplatin; Ipilimumab; Nivolumab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Vaibhav Sahai, MBBS, MS
• Organization: University of Michigan Rogel Cancer Center

vsahai@med.umich.edu

734-936-4991

Study Officials

• Vaibhav Sahai, MBBS, MS

  University of Michigan Rogel Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2017
• First Posted: April 5, 2017
• Study Start: September 8, 2017
• Primary Completion: December 3, 2019
• Study Completion: June 7, 2021
• Last Updated: October 28, 2022
• Results First Posted: August 10, 2021

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)