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

NCT ID: NCT03785873

Last Updated: 2024-12-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-22
• Study Completion Date: 2024-11-15

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Nal-Irinotecan and Nivolumab

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: DRUG

Intravenous (IV) infusion

Nanoliposomal-Irinotecan

Intervention Type: DRUG

Intravenous (IV) infusion

5-Fluorouracil

Intervention Type: DRUG

Intravenous (IV) infusion

Leucovorin

Intervention Type: DRUG

Intravenous (IV) infusion

Interventions

Nivolumab

Intravenous (IV) infusion

Intervention Type: DRUG

Nanoliposomal-Irinotecan

Intravenous (IV) infusion

Intervention Type: DRUG

5-Fluorouracil

Intravenous (IV) infusion

Intervention Type: DRUG

Leucovorin

Intravenous (IV) infusion

Intervention Type: DRUG

Other Intervention Names

Opdivo®, BMS-936558, MDX-1106, ONO-4538; Onivyde®; 5-FU

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion

• 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.
• No known HIV, Hepatitis B or Hepatitis C infection that is untreated and/or with a detectable viral load.
• Patients must not have uncontrolled intercurrent illness including, but not limited to, interstitial lung disease, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia.
• No known medical condition (e.g. a condition associated with uncontrolled diarrhea such as ulcerative colitis or acute diverticulitis) that, in the investigator's opinion, would increase the risk associated with study participation or interfere with the interpretation of safety results.
• Patients must not be on warfarin, strong CYP3A4 inducers (such as phenytoin, phenobarbital, primidone, carbamazepine, rifampin, rifabutin, rifapentine or St. John's wort), strong CYP3A4 inhibitors (such as ketoconazole, clarithromycin, indinavir, itraconazole, lopinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telaprevir, voriconazole), and strong UGT1A1 inhibitors (such as atazanavir, gemfibrozil, indinavir and ketoconazole).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ipsen

INDUSTRY

Sponsor Role: collaborator

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

University of Michigan Rogel Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Vaibhav Sahai, MBBS, MS

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

Locations

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, United States

Cancer and Hematology Centers of Western Michigan

Grand Rapids, Michigan, United States

University of Utah

Salt Lake City, Utah, United States

Virginia Mason

Seattle, Washington, United States

University of Wisconsin

Madison, Wisconsin, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 39701097 (View on PubMed)

Other Identifiers

HUM00151852

Identifier Type: OTHER

Identifier Source: secondary_id

UMCC 2018.101

Identifier Type: -

Identifier Source: org_study_id