Biliary Tract NeoplasmsPhase 2NCT03101566
Study of Nivolumab in Combination With Gemcitabine/Cisplatin or Ipilimumab for Patients With Advanced Unresectable Biliary Tract Cancer
A Phase 2 study testing Gemcitabine, Cisplatin and Ipilimumab in people with Biliary Tract Neoplasms, run by University of Michigan Rogel Cancer Center at 7 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Biliary Tract Neoplasms
- What is being tested?
- Gemcitabine, Cisplatin and Ipilimumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 75 participants
- Where
- 7 sitesUnited States
- Study dates
- 8 Sep 2017to 7 Jun 2021
- Phase
- Phase 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 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
Show all 10Show fewer
- 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
Who cannot join
- 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.
Show all 13Show fewer
- 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.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109
Emory University
Atlanta, Georgia, 30322
Northwestern University
Chicago, Illinois, 60611
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
University of Wisconsin
Madison, Wisconsin, 53705
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
University of Washington
Seattle, Washington, 98109
About this study
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]
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
- Being tested
- Gemcitabine, Cisplatin, Ipilimumab, Nivolumab
- 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.
GemcitabineDrug
Gemcitabine 1000 mg/m2 IV
CisplatinDrug
Cisplatin 25 mg/m2 IV
IpilimumabDrug
Ipilimumab 1 mg/kg IV
NivolumabDrug
Nivolumab 360 mg or 240 mg IV
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Ipilimumab; Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 Months
Secondary outcomes (3)
Median Progression Free Survival Time
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.
Measured: Patients will be followed until death, withdrawal from study, or until 2 years, whichever is earliest
Median Overall Survival Time
The median overall survival time following the initiation of treatment.
Measured: Patients will be followed until death, withdrawal from study, or until 2 years, whichever is earliest
Overall Response Rate (ORR)
Overall Response Rate will be determined as per the combined RECIST v1.1 and irRECIST criteria
Measured: Up to two years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2017
- Study start8 Sep 2017
- Primary completion3 Dec 2019
- Study completion7 Jun 2021
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 NeoplasmsStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan Rogel Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Vaibhav Sahai, MBBS, MS, Principal investigator, University of Michigan Rogel Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03101566
- Sponsor's protocol ID
- UMCC 2017.026
- Other IDs
- HUM00126271, HUM00130035
- Status last verified
- Sep 2022
- First submitted
- 30 Mar 2017
- Last updated
- 28 Oct 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 35895381
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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]
- ClinicalTrials.gov ID
- NCT03101566
- Acronym / sponsor ID
- UMCC 2017.026
- Conditions
- Biliary Tract Neoplasms
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 75 participants (actual)
- Lead sponsor
- University of Michigan Rogel Cancer CenterUniversity, hospital or other
- Study start
- 8 Sep 2017 (actual)
- Primary completion
- 3 Dec 2019 (actual)
- Study completion
- 7 Jun 2021 (actual)
- First posted
- 5 Apr 2017 (actual)
- Results
- Posted 10 Aug 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Gemcitabine + Cisplatin + Nivolumab | Experimental | Drug: Gemcitabine, Drug: Cisplatin, Drug: NivolumabDrug: 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 |
| Nivolumab + Ipilimumab | Experimental | Drug: Ipilimumab, Drug: NivolumabDrug: Ipilimumab 1 mg/kg IV on day 1 every 6 weeks Drug: Nivolumab 240 mg IV on day 1 every 2 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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)
Key exclusion criteria (13 listed)
- 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.
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 |
|---|---|---|
| GemcitabineGemcitabine 1000 mg/m2 IV | Drug | Gemcitabine + Cisplatin + Nivolumab |
| CisplatinCisplatin 25 mg/m2 IV | Drug | Gemcitabine + Cisplatin + Nivolumab |
| IpilimumabIpilimumab 1 mg/kg IV | Drug | Nivolumab + Ipilimumab |
| NivolumabNivolumab 360 mg or 240 mg IV | Drug | Gemcitabine + Cisplatin + Nivolumab, Nivolumab + Ipilimumab |
Primary outcome
The Percentage of Patients Alive and Without Progression at 6 Months Following the Initiation of Treatment
Time frame: 6 Months
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.
3 secondary outcomes
Median Progression Free Survival Time
Time frame: Patients will be followed until death, withdrawal from study, or until 2 years, whichever is earliest
Median Overall Survival Time
Time frame: Patients will be followed until death, withdrawal from study, or until 2 years, whichever is earliest
Overall Response Rate (ORR)
Time frame: Up to two years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35895381Sahai 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.
- Individual participant dataSharing planned: No
Related trials for Biliary Tract Neoplasms
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 Rogel Cancer Center
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Gemcitabine, Cisplatin and Ipilimumab in people with Biliary Tract Neoplasms, run by University of Michigan Rogel Cancer Center at 7 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 10 inclusion and 13 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 28 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 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 phase mean?
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 10 Aug 2021). 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?
The Percentage of Patients Alive and Without Progression at 6 Months Following the Initiation of Treatment (time frame: 6 Months). 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 NCT03101566, 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 28 Oct 2022.