Phase Ib/II Trial of Nal-Irinotecan and Nivolumab as Second-Line Treatment in Patients With Advanced Biliary Tract Cancer

NCT03785873 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: UMCC 2018.101HUM00151852
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study is to test the effectiveness (how well the drug works), safety, and tolerability of the investigational drug combination of nivolumab plus nanoliposomal-irinotecan, 5-fluorouracil, and leucovorin for patients with advanced or metastatic biliary tract cancer after progression on first-line systemic therapy.

Conditions

Biliary Tract Cancer

Outcome Measures

Primary Outcomes (2)

• Phase Ib: Incidence of Dose-limiting Toxicities (DLTs) of Drug Combination Nanoliposomal-Irinotecan, 5-fluorouracil, Leucovorin and Nivolumab

  Adverse events will be graded according to NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0.The patients accrued to the phase 2 portion of the trial were also observed for DLT during the first cycle of therapy given the same dose level was used.

  At 4 weeks after initiation of study treatment

• Median Progression-Free Survival (PFS)

  Based on Kaplan-Meier estimates.

  Up to 2 years after last dose of study treatment, average of 4 months

Secondary Outcomes (3)

• Incidence of Treatment-related Adverse Events

  Until discontinuation of study treatment, up to approximately 2 years after initiating study treatment or 3 years after first date of treatment initiation for those that remain on treatment

• Overall Response Rate (ORR)

  Up to 2 years after last dose of study treatment, average of 8.5 months

• Median Overall Survival (OS)

  Up to 2 years

Study Arms (1)

Nal-Irinotecan and Nivolumab

EXPERIMENTAL

Drug: Nivolumab; Drug: Nanoliposomal-Irinotecan; Drug: 5-Fluorouracil; Drug: Leucovorin

Interventions

Nivolumab DRUG

Intravenous (IV) infusion

Also known as: Opdivo®, BMS-936558, MDX-1106, ONO-4538

Nal-Irinotecan and Nivolumab

5-Fluorouracil DRUG

Intravenous (IV) infusion

Also known as: 5-FU

Nal-Irinotecan and Nivolumab

Leucovorin DRUG

Intravenous (IV) infusion

Nal-Irinotecan and Nivolumab

Nanoliposomal-Irinotecan DRUG

Intravenous (IV) infusion

Also known as: Onivyde®

Nal-Irinotecan and Nivolumab

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 carcinoma 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 with mixed hepatocellular and cholangiocarcinoma histology are excluded.
• Patients must have received one and only one prior systemic therapy for advanced disease. Prior therapies must have not included irinotecan or PD- 1/PD-L1 antibody. Patient should have either progressed on or within 6 months of first-line systemic therapy or deemed intolerant of that therapy.
• Prior surgical resection, radiation, chemoembolization, radioembolization or other local ablative therapies are permitted if completed ≥ 4 weeks prior to registration AND if patient has recovered to ≤ grade 1 toxicity.
• Patients must have radiographically 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 lesion.
• Age ≥18 years
• Child-Pugh score of less than 7
• ECOG performance status of 0-1
• 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 (per protocol) assessed ≤2 weeks prior to registration

You may not qualify if:

• Must not have received systemic steroid therapy, or any other form of immunosuppressive therapy within 14 days prior to registration. Short bursts of steroids of 5-7 days (for COPD exacerbation or other similar indication) are allowed.
• No prior history of solid organ transplantation or brain metastasis (unless treated, asymptomatic and stable).
• 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 (afebrile for \> 48 hours off antibiotics).
• Must not have received a live vaccine within 30 days of registration
• 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 5-fluorouracil, nal- irinotecan 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 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 14 days of registration are excluded. Inhaled, ocular, intra-articular, intra-nasal or topical steroids, and adrenal replacement steroid doses \>10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
• No known UGT1A1\* variants or Gilbert's syndrome
• Prisoners or subjects who are involuntarily incarcerated, or compulsorily detained for treatment of either a psychiatric or physical (e.g. infectious disease) illness would be excluded.
• No known hypersensitivity to 5-fluorouracil, leucovorin, irinotecan, and/or nivolumab.
• Must not have ongoing bowel obstruction.

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead
• Ipsen: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (5)

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Cancer and Hematology Centers of Western Michigan

Grand Rapids, Michigan, 49503, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Virginia Mason

Seattle, Washington, 98101, United States

Location

University of Wisconsin

Madison, Wisconsin, 53705, United States

Location

Related Publications (1)

• Sahai V, Griffith KA, Lin BS, Soares HP, Chandana SR, Crysler O, Kumar-Sinha C, Enzler T, Dippman D, Gunchick V, Zalupski MM. BilT03: Phase 1b/2 multicenter trial of nivolumab with 5-fluorouracil and liposomal irinotecan for previously treated advanced biliary tract cancer. Med. 2025 Apr 11;6(4):100547. doi: 10.1016/j.medj.2024.10.024. Epub 2024 Dec 18.

  PMID: 39701097 DERIVED

MeSH Terms

Conditions

Biliary Tract Neoplasms

Interventions

Nivolumab; irinotecan sucrosofate; Fluorouracil; Leucovorin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Results Point of Contact

• Title: University of Michigan Rogel Cancer Center ClinicalTrials.gov Admin
• Organization: University of Michigan Rogel Cancer Center

ClinicalTrialsgov_CCAdmin@umich.edu

734-936-9499

Study Officials

• Vaibhav Sahai, MBBS, MS

  University of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2018
• First Posted: December 24, 2018
• Study Start: May 22, 2019
• Primary Completion: November 15, 2024
• Study Completion: November 15, 2024
• Last Updated: February 13, 2026
• Results First Posted: February 13, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, 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.

Locations

US (5)