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Pembrolizumab, a Monoclonal Antibody Against PD-1, in Combination With Capecitabine and Oxaliplatin (CAPOX) in People With Advanced Biliary Tract Carcinoma (BTC)

Phase 2
Completed
Conditions
Liver Cancer
Biliary Tract Neoplasms
Cholangiocarcinoma
Bile Duct Cancer
Gallbladder Cancer
Interventions
Biological: Pembrolizumab (MK-3475)
Drug: Oxaliplatin
Drug: Capecitabine
Registration Number
NCT03111732
Lead Sponsor
National Cancer Institute (NCI)
Brief Summary

Background:

Biliary tract cancers are rare but they are serious. Researchers want to see if a certain drug helps the immune system fight cancer cells. The drug is called pembrolizumab. It may work even better with two chemotherapy drugs that are widely used to treat gastrointestinal cancers.

Objective:

To study if pembrolizumab given with capecitabine and oxaliplatin (CAPOX) increases the time it takes for a person's biliary tract cancer to get worse.

Eligibility:

People age 18 and older with previously treated biliary tract cancer that has spread to other parts of the body

Design:

Participants will be screened with tests as part of their regular cancer care.

Each study cycle is 3 weeks.

For 6 cycles, participants will:

Get pembrolizumab and oxaliplatin on day 1 of each cycle. They will be given in an intravenous (IV) catheter.

Take capecitabine by mouth for 2 weeks then have 1 week without it.

Participants will complete a patient diary.

Starting with cycle 7, participants will get only pembrolizumab. They will get it once every 3 weeks.

On day 1 of every cycle, participants will have:

Physical exam

Review of symptoms and how well they do normal activities

Blood tests

Every 9 weeks, they will have a scan.

Participants may have tumor samples taken.

Participants will have a final visit about 1 month after they stop the study drug. After that, they will be contacted by phone or email yearly.

Detailed Description

Background:

* The most compelling argument in favor of testing immune-based strategies (and anti-Programmed cell death protein 1 (PD1) therapy in particular) in biliary tract cancers (BTC) is that chronic inflammation appears to be the most common etiologic factor in the development of biliary tract cancer.

* Single-agent activity has been shown for PD1-directed therapy in BTC. Given the potential for oxaliplatin-induced immunogenic cell death we would like to evaluate the combination of capecitabine and oxaliplatin (CAPOX) chemotherapy with pembrolizumab.

Objective:

To determine the 5-month progression free survival (PFS) of Pembrolizumab in combination with CAPOX in patients with advanced biliary tract carcinoma.

Eligibility:

* Histologically confirmed diagnosis biliary tract carcinoma OR histopathological confirmation of carcinoma in the setting of clinical and radiological characteristics which, together with the pathology, are highly suggestive of a diagnosis of biliary tract carcinoma.

* Patients must have at least one prior chemotherapeutic regimen.

* Patients must have disease that is not amenable to potentially curative resection.

* No prior treatment with oxaliplatin.

Design:

The proposed study is a phase II study of Pembrolizumab in combination with CAPOX in patients with advanced biliary tract carcinoma

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
11
Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
1/Arm 1Pembrolizumab (MK-3475)Pembrolizumab plus Oxaliplatin plus Capecitabine
1/Arm 1CapecitabinePembrolizumab plus Oxaliplatin plus Capecitabine
1/Arm 1OxaliplatinPembrolizumab plus Oxaliplatin plus Capecitabine
Primary Outcome Measures
NameTimeMethod
Progression Free Survival (PFS)5 Months

Median amount of time subject survives without disease progression for 5 months after treatment. Disease progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The appearance of one or more new lesions is also considered progressions.

Secondary Outcome Measures
NameTimeMethod
Number of Participants Obtaining a Complete Response (CR) and Partial Response (PR)Every 9 Weeks, until disease progression or patient is taken off the trial, whichever comes first, approximately 36 weeks.

Number of participants obtaining CR and PR per the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria of all evaluable patients. CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR is at least a 30% decrease in the sum of the diameters of target lesions,taking as reference the baseline sum of diameters.

Number Participants With Grade 1-4 Adverse Events Unrelated, Unlikely, Possibly, Probably and Definitely Related to Pembrolizumab30 Days After Enrollment

Here is the number of participants with grade 1-4 adverse events unrelated, unlikely, possibly, probably and definitely related to study drug assessed by the Common Terminology Criteria for Adverse Events v4.0. Mild (Grade1), moderate (Grade 2), severe (Grade 3), and life-threatening or disabling (Grade 4).

Number Participants With Grade 1-4 Adverse Events Unrelated, Unlikely, Possibly, Probably and Definitely Related to Oxaliplatin30 Days After Enrollment

Here is the number of participants with grade 1-4 adverse events unrelated, unlikely, possibly, probably and definitely related to study drug assessed by the Common Terminology Criteria for Adverse Events v4.0. Mild (Grade1), moderate (Grade 2), severe (Grade 3), and life-threatening or disabling (Grade 4).

Overall SurvivalDeath, approximately 48 weeks after stopping therapy.

Median amount of time subject survives after therapy.

Number of Participants With Grade 1-4 Adverse Events Unrelated, Unlikely, Possibly, and Probably Related to Capecitabine30 Days After Enrollment

Here is the number of participants with grade 1-4 adverse events unrelated, unlikely, possibly, and probably related to study drug assessed by the Common Terminology Criteria for Adverse Events v4.0. Mild (Grade1), moderate (Grade 2), severe (Grade 3), and life-threatening or disabling (Grade 4).

Trial Locations

Locations (1)

National Institutes of Health Clinical Center

🇺🇸

Bethesda, Maryland, United States

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