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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)

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ClinicalTrials.gov Identifier: NCT03111732
Recruitment Status : Recruiting
First Posted : April 13, 2017
Last Update Posted : February 12, 2020
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Tracking Information
First Submitted Date  ICMJE April 12, 2017
First Posted Date  ICMJE April 13, 2017
Last Update Posted Date February 12, 2020
Actual Study Start Date  ICMJE June 14, 2017
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 24, 2019)
5-month PFS [ Time Frame: 5 Months ]
Median amount of time subject survives without disease progression for 5 months after treatment
Original Primary Outcome Measures  ICMJE
 (submitted: April 12, 2017)
Median amount of time subject survives without disease progression for 5 month after treatment [ Time Frame: 5 Months ]
Change History Complete list of historical versions of study NCT03111732 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 9, 2018)
  • safety [ Time Frame: 30 Days After Enrollment ]
    List of adverse event frequency
  • response rate [ Time Frame: Every 9 Weeks ]
    Proportion of patients obtaining CR and PR per RECIST 1.1 criteria of all evaluable patients
  • overall survival [ Time Frame: Death ]
    Median amount of time subject survives after therapy
Original Secondary Outcome Measures  ICMJE
 (submitted: April 12, 2017)
  • List of adverse event frequency [ Time Frame: 30 Days After Enrollment ]
  • Proportion of patients obtaining CR and PR per RECIST 1.1 criteria of all evaluable patients [ Time Frame: Every 9 Weeks ]
  • Median amount of time subject survives after therapy [ Time Frame: Death ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pembrolizumab, a Monoclonal Antibody Against PD-1, in Combination With Capecitabine and Oxaliplatin (CAPOX) in People With Advanced Biliary Tract Carcinoma (BTC)
Official Title  ICMJE 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)
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-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

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Biliary Tract Neoplasms
  • Cholangiocarcinoma
  • Bile Duct Cancer
  • Liver Cancer
  • Gallbladder Cancer
Intervention  ICMJE
  • Biological: Pembrolizumab (MK-3475)
    200 mg will be administered as an IV infusion on Day 1 of each 21 day cycle
  • Drug: Oxaliplatin
    130mg/m(2) IV Infusion will be administered as an IV infusion on Day 1 of cycles 1-6
  • Drug: Capecitabine
    750 mg/m(2) will be administered orally twice a day on Days 1-14 of cycles 1-6
Study Arms  ICMJE Experimental: 1/Arm 1
Pembrolizumab plus Oxaliplatin plus Capecitabine
Interventions:
  • Biological: Pembrolizumab (MK-3475)
  • Drug: Oxaliplatin
  • Drug: Capecitabine
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 12, 2017)
19
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2020
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Elizabeth Q Akoth (240) 858-3154 elizabeth.akoth@nih.gov
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03111732
Other Study ID Numbers  ICMJE 170082
17-C-0082
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Tim F Greten, M.D. National Cancer Institute (NCI)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date January 14, 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP