Clinical Trials /

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

NCT03111732

Description:

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.

Related Conditions:
  • Ampulla of Vater Carcinoma
  • Biliary Tract Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab, a Monoclonal Antibody Against PD-1, in Combination With Capecitabine and Oxaliplatin (CAPOX) in People With Advanced Biliary Tract Carcinoma (BTC)
  • Official Title: A Phase 2 Study of Pembrolizumab, a Monoclonal Antibody Against PD-1, in Combination With Capecitabine and Oxaliplatin (CAPOX) in Subjects With Advanced Biliary Tract Carcinoma (BTC)

Clinical Trial IDs

  • ORG STUDY ID: 170082
  • SECONDARY ID: 17-C-0082
  • NCT ID: NCT03111732

Conditions

  • Biliary Tract Neoplasms
  • Cholangiocarcinoma
  • Bile Duct Cancer
  • Liver Cancer
  • Gallbladder Cancer

Interventions

DrugSynonymsArms
Pembrolizumab (MK-3475)1/Arm 1
Oxaliplatin1/Arm 1
Capecitabine1/Arm 1

Purpose

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-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 CAPOX chemotherapy with pembrolizumab.

      Objective:

      To determine the 5-month 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
    

Trial Arms

NameTypeDescriptionInterventions
1/Arm 1ExperimentalPembrolizumab plus Oxaliplatin plus Capecitabine
  • Pembrolizumab (MK-3475)
  • Oxaliplatin
  • Capecitabine

Eligibility Criteria

        -  INCLUSION CRITERIA:

          -  Patients must have histopathological confirmation of biliary tract carcinoma (BTC) by
             the Laboratory of Pathology of the NCI prior to entering this study 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. The term BTC includes intra- or
             extrahepatic cholangiocarcinoma, gallbladder cancer or ampullary cancer.

          -  Patients must have disease that is not amenable to potentially curative resection.
             Patients must have received, been intolerant of or refused at least one line of
             chemotherapy.

          -  Patients must have at least one focus of measurable metastatic disease per RECIST 1.1.

          -  Patients must have at least one focus of metastatic disease that is amenable to pre-
             and on-treatment biopsies. Ideally the biopsied lesion should not be one of the target
             measurable lesions, although this can be up to the discretion of the investigators.

          -  Age greater than or equal to 18 years

          -  ECOG performance status 0-1

          -  Patients must have normal organ and marrow function as defined below:

               -  leukocytes greater than or equal to 3,000/mcL

               -  absolute neutrophil count greater than or equal to 1,000/mcL

               -  platelets greater than or equal to 100,000/mcL

               -  total bilirubin less than or equal to 2 xULN

               -  Serum albumin greater than or equal to 2.5g/dl

               -  Patients are eligible with ALT or AST up to 5 x ULN.

               -  creatinine <1.5X institution upper limit of normal OR creatinine clearance
                  greater than or equal to 45 mL/min/1.73 m^2 for patients with creatinine levels
                  above institutional normal

          -  Patients must have recovered from any acute toxicity related to prior therapy,
             including surgery. Toxicity should be less than or equal to grade 1 or returned to
             baseline.

          -  Patients must not have other invasive malignancies within the past 5 years (with the
             exception of non-melanoma skin cancers, non-invasive bladder cancer or localized
             prostate cancer for whom systemic therapy is not required).

          -  Patient must be able to understand and willing to sign a written informed consent
             document.

          -  The effects of Pembrolizumab in combination with Capecitabine and Oxaliplatin on the
             developing human fetus are unknown. For this reason, women of child-bearing potential
             and men must agree to use adequate contraception (hormonal or barrier method of birth
             control; abstinence) prior to study entry, for the duration of study participation and
             up to 120 days after the last dose of the drug. Should a woman become pregnant or
             suspect she is pregnant while she or her partner is participating in this study, she
             should inform her treating physician immediately.

        EXCLUSION CRITERIA:

          -  Patients who have had standard of care chemotherapy, large field radiotherapy, or
             major surgery must wait 2 weeks prior to entering the study.

          -  Previous treatment with immune checkpoint inhibitors.

          -  Patients who have undergone prior liver transplantation are ineligible.

          -  Patients with known brain metastases will be excluded from this clinical trial because
             of their poor prognosis and because they often develop progressive neurologic
             dysfunction that would confound the evaluation of neurologic and other adverse events.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             systemic infection, symptomatic congestive heart failure, unstable angina pectoris,
             cardiac arrhythmia (excluding insignificant sinus bradycardia and sinus tachycardia)
             or psychiatric illness/social situations that would limit compliance with study
             requirements.

          -  History of (non-infectious) pneumonitis that required steroids, evidence of
             interstitial lung disease or active, non-infectious pneumonitis.

          -  History of chronic autoimmune disease (e.g., Addison s disease, multiple sclerosis,
             Graves disease, Hashimoto s thyroiditis, rheumatoid arthritis, hypophysitis, etc.)
             with symptomatic disease within the 3 years before randomization. Note: Active
             vitiligo or a history of vitiligo will not be a basis for exclusion.

          -  Dementia or significantly altered mental status that would prohibit the understanding
             or rendering of Information and Consent and compliance with the requirements of the
             protocol

          -  Active or history of inflammatory bowel disease (colitis, Crohn s), irritable bowel
             disease, celiac disease, or other serious, chronic, gastrointestinal conditions
             associated with diarrhea. Active or history of systemic lupus erythematosus or Wegener
             s granulomatosis.

          -  Currently receiving immunosuppressive doses of steroids or other immunosuppressive
             medications (inhaled and topical steroids are permitted)

          -  History of sarcoidosis syndrome.

          -  Known history of active tuberculosis.

          -  Patients should not be vaccinated with live attenuated vaccines within 1 month of
             starting pembrolizumab treatment.

          -  Active hepatitis B or C infection.

          -  HIV-positive patients receiving anti-retroviral therapy are excluded from this study
             due to the possibility of pharmacokinetic interactions between antiretroviral
             medications and pembrolizumab. HIV positive patients not receiving antiretroviral
             therapy are excluded due to the possibility that pembrolizumab may worsen their
             condition and the likelihood that the underlying condition may obscure the attribution
             of adverse events.

          -  History of hypersensitivity reaction to human or mouse antibody products.

          -  Female patients who are pregnant or breastfeeding. Because there is an unknown but
             potential risk for adverse events in nursing infants secondary to treatment of the
             mother with Pembrolizumab in combination with Capecitabine and Oxaliplatin,
             breastfeeding should be discontinued.

          -  Patients with unhealed surgical wounds for more than 30 days.

          -  Prior therapy with oxaliplatin
      
Maximum Eligible Age:99 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:5-month
Time Frame:5 Months
Safety Issue:
Description:Median amount of time subject survives without disease progression for 5 months after treatment

Secondary Outcome Measures

Measure:safety
Time Frame:30 Days After Enrollment
Safety Issue:
Description:List of adverse event frequency
Measure:response rate
Time Frame:Every 9 Weeks
Safety Issue:
Description:Proportion of patients obtaining CR and PR per RECIST 1.1 criteria of all evaluable patients
Measure:overall survival
Time Frame:Death
Safety Issue:
Description:Median amount of time subject survives after therapy

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:National Cancer Institute (NCI)

Trial Keywords

  • Immune-Based Strategies
  • Anti-PD1 Therapy
  • Chronic Inflammation
  • Combination Chemotherapy

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