Biliary Tract CancerPhase 1/2NCT03785873

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

A Phase 1/2 study testing Nivolumab, Nanoliposomal-Irinotecan and 5-Fluorouracil in people with Biliary Tract Cancer, run by University of Michigan Rogel Cancer Center at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Biliary Tract Cancer
What is being tested?: Nivolumab, Nanoliposomal-Irinotecan and 5-Fluorouracil
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 34 participants
Where: 5 sitesUnited States
Study dates: 22 May 2019to 15 Nov 2024
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

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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

Who cannot join

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

Show all 19Show fewer

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).

Trial locations and contacts

5 sites in 1 country.

City, postcode or hospital

5 sites in 1 country

United States5 sites

University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, 48109
Cancer and Hematology Centers of Western Michigan
Grand Rapids, Michigan, 49503
University of Wisconsin
Madison, Wisconsin, 53705
University of Utah
Salt Lake City, Utah, 84132
Virginia Mason
Seattle, Washington, 98101

Other trials in United States

About this study

Official title: A Single Arm Phase Ib/II Multi-Center Study of Nivolumab in Combination With Nanoliposomal-Irinotecan, 5-Fluorouracil, and Leucovorin as Second Line Therapy for Patients With Advanced Biliary Tract Cancer

Conditions: Biliary Tract Cancer
Being tested: Nivolumab, Nanoliposomal-Irinotecan, 5-Fluorouracil, Leucovorin
Medical subject headings: Biliary Tract Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

NivolumabDrug
Also called Opdivo®, BMS-936558, MDX-1106, ONO-4538
Intravenous (IV) infusion
Nanoliposomal-IrinotecanDrug
Also called Onivyde®
Intravenous (IV) infusion
5-FluorouracilDrug
Also called 5-FU
Intravenous (IV) infusion
LeucovorinDrug
Intravenous (IV) infusion

Study groups in NCT03785873
Study group	Role	What they receive
Nal-Irinotecan and Nivolumab	Experimental	Not described Receives: Drug: Nivolumab; Drug: Nanoliposomal-Irinotecan; Drug: 5-Fluorouracil; Drug: Leucovorin

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: At 4 weeks after initiation of study treatment
Median Progression-Free Survival (PFS)
Based on Kaplan-Meier estimates.
Measured: Up to 2 years after last dose of study treatment, average of 4 months

Secondary outcomes (3)

Incidence of Treatment-related Adverse Events
Reportable adverse events are defined by the study protocol and graded according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE) v5.0. The maximum grade per type, per patient is reported below.
Measured: 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)
Determined per the combined Response Evaluation Criteria in Solid Tumours (RECISTv1.1) and immune-related RECIST (irRECIST) criteria. Complete Response and Partial Response are included.
Measured: Up to 2 years after last dose of study treatment, average of 8.5 months
Median Overall Survival (OS)
Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

22 May 201915 Nov 2024

First posted24 Dec 2018
Study start22 May 2019
Primary completion15 Nov 2024
Study completion15 Nov 2024

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Biliary Tract CancerStudies of the same condition, open and under way.
More trials run by University of Michigan Rogel Cancer CenterThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 34 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03785873
Sponsor's protocol ID: UMCC 2018.101
Other IDs: HUM00151852
Status last verified: Feb 2026
First submitted: 20 Dec 2018
Last updated: 13 Feb 2026
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: IPD that underlie the results published in peer reviewed research articles, after deidentification.

Publications

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.
PubMed 39701097

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruitingPhase 2/3
A Study of CTX-009 in Combination With Paclitaxel in Adult Patients With Unresectable Advanced, Metastatic or Recurrent Biliary Tract Cancers (COMPANION-002)
Biliary Tract Cancer, Cholangiocarcinoma
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
RecruitingObservational study
Tissue Procurement and Natural History Study of Patients With Malignant Mesothelioma
Thymoma, Stomach Neoplasms
Active, not recruitingPhase 2
Durvalumab and Tremelimumab in Combination With Propranolol and Chemotherapy for Treatment of Advanced Hepatopancreabiliary Tumors (BLOCKED)
Pancreatic Cancer, Hepatocellular Cancer
Not yet recruitingPhase 3
Hepatic Arterial Infusion Chemotherapy Versus Capecitabine as Adjuvant Therapy for Resected Biliary Tract Cancer
Biliary Tract Cancer, Cholangiocarcinoma

All Biliary Tract Cancer trials

Study at a glance

From the registry record, last updated by the sponsor on 13 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Single Arm Phase Ib/II Multi-Center Study of Nivolumab in Combination With Nanoliposomal-Irinotecan, 5-Fluorouracil, and Leucovorin as Second Line Therapy for Patients With Advanced Biliary Tract Cancer
ClinicalTrials.gov ID: NCT03785873
Acronym / sponsor ID: UMCC 2018.101
Conditions: Biliary Tract Cancer
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 34 participants (actual)
Lead sponsor: University of Michigan Rogel Cancer CenterUniversity, hospital or other
Collaborators: Ipsen, Bristol-Myers Squibb
Study start: 22 May 2019 (actual)
Primary completion: 15 Nov 2024 (actual)
Study completion: 15 Nov 2024 (actual)
First posted: 24 Dec 2018 (actual)
Results: Posted 13 Feb 2026

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Nal-Irinotecan and Nivolumab	Experimental	Drug: Nivolumab, Drug: Nanoliposomal-Irinotecan, Drug: 5-Fluorouracil, Drug: Leucovorin

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (11 listed)

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

Key exclusion criteria (19 listed)

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).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
NivolumabAlso: Opdivo®, BMS-936558, MDX-1106, ONO-4538Intravenous (IV) infusion	Drug	Nal-Irinotecan and Nivolumab
Nanoliposomal-IrinotecanAlso: Onivyde®Intravenous (IV) infusion	Drug	Nal-Irinotecan and Nivolumab
5-FluorouracilAlso: 5-FUIntravenous (IV) infusion	Drug	Nal-Irinotecan and Nivolumab
LeucovorinIntravenous (IV) infusion	Drug	Nal-Irinotecan and Nivolumab

Primary outcome

Phase Ib: Incidence of Dose-limiting Toxicities (DLTs) of Drug Combination Nanoliposomal-Irinotecan, 5-fluorouracil, Leucovorin and Nivolumab
Time frame: At 4 weeks after initiation of study treatment
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.
Median Progression-Free Survival (PFS)
Time frame: Up to 2 years after last dose of study treatment, average of 4 months
Based on Kaplan-Meier estimates.

3 secondary outcomes

Incidence of Treatment-related Adverse Events
Time frame: 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)
Time frame: Up to 2 years after last dose of study treatment, average of 8.5 months
Median Overall Survival (OS)
Time frame: Up to 2 years

Results and safety

Results posted to the registry on 13 Feb 2026, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Phase 1b: Nal-Irinotecan and Nivolumab	10	7
Phase 2: Nal-Irinotecan and Nivolumab	20	14

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

Time frame: At 4 weeks after initiation of study treatment. Count of participants. Unit: Participants

Measure	Nal-Irinotecan and Nivolumab n = 30
Value	4

Population analysed: All study patients have been combined into one cohort as they all received the same treatment (Irinotecan 70 mg/m2, 5-Fluorouracil 2400 mg/m2, Leucovorin 400 mg/m2, Nivolumab 240 mg)

Primary outcome: Median Progression-Free Survival (PFS)

Time frame: Up to 2 years after last dose of study treatment, average of 4 months. Median (95% Confidence Interval). Unit: months

Measure	Nal-Irinotecan and Nivolumab n = 30
Value	4.1 (1.9 to 9.9)

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: All adverse event data (serious and non-serious) collected from the time of initial study treatment administration through 100 days after the last dose of study treatment, up to 2 years, and an average of 8.5 months per subject.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Nal-Irinotecan and Nivolumab	22 of 30 (73.3%)	28 of 30 (93.3%)	26 of 30

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 39701097Sahai 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.
Individual participant dataSharing planned: Yes. IPD that underlie the results published in peer reviewed research articles, after deidentification.

Related trials for Biliary Tract Cancer

Active, not recruitingPhase 2/3
A Study of CTX-009 in Combination With Paclitaxel in Adult Patients With Unresectable Advanced, Metastatic or Recurrent Biliary Tract Cancers (COMPANION-002)
Biliary Tract Cancer, Cholangiocarcinoma
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
RecruitingObservational study
Tissue Procurement and Natural History Study of Patients With Malignant Mesothelioma
Thymoma, Stomach Neoplasms
Active, not recruitingPhase 2
Durvalumab and Tremelimumab in Combination With Propranolol and Chemotherapy for Treatment of Advanced Hepatopancreabiliary Tumors (BLOCKED)
Pancreatic Cancer, Hepatocellular Cancer
Not yet recruitingPhase 3
Hepatic Arterial Infusion Chemotherapy Versus Capecitabine as Adjuvant Therapy for Resected Biliary Tract Cancer
Biliary Tract Cancer, Cholangiocarcinoma

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Vaibhav Sahai, MBBS, MS principal investigator

University of Michigan

5 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Nivolumab, Nanoliposomal-Irinotecan and 5-Fluorouracil in people with Biliary Tract Cancer, run by University of Michigan Rogel Cancer Center at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Feb 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase Ib: Incidence of Dose-limiting Toxicities (DLTs) of Drug Combination Nanoliposomal-Irinotecan, 5-fluorouracil, Leucovorin and Nivolumab (time frame: At 4 weeks after initiation of study treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03785873, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2026.