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

NCT03111732 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 17008217-C-0082
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  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.

  5 Months

Secondary Outcomes (5)

• 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.

• Overall Survival

  Death, approximately 48 weeks after stopping therapy.

• Number Participants With Grade 1-4 Adverse Events Unrelated, Unlikely, Possibly, Probably and Definitely Related to Pembrolizumab

  30 Days After Enrollment

• Number Participants With Grade 1-4 Adverse Events Unrelated, Unlikely, Possibly, Probably and Definitely Related to Oxaliplatin

  30 Days After Enrollment

• Number of Participants With Grade 1-4 Adverse Events Unrelated, Unlikely, Possibly, and Probably Related to Capecitabine

  30 Days After Enrollment

Other Outcomes (1)

• Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)

  Date treatment consent signed to date off study, approximately 38 months and 25 days.

Study Arms (1)

1/Arm 1

EXPERIMENTAL

Pembrolizumab plus Oxaliplatin plus Capecitabine

Biological: Pembrolizumab (MK-3475); Drug: Oxaliplatin; Drug: Capecitabine

Interventions

Pembrolizumab (MK-3475) BIOLOGICAL

200 mg will be administered as an IV infusion on Day 1 of each 21 day cycle

1/Arm 1

Oxaliplatin DRUG

130mg/m(2) IV Infusion will be administered as an IV infusion on Day 1 of cycles 1-6

1/Arm 1

Capecitabine DRUG

750 mg/m(2) will be administered orally twice a day on Days 1-14 of cycles 1-6

1/Arm 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histopathological confirmation of biliary tract carcinoma (BTC) by the Laboratory of Pathology of the National Cancer Institute (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 Response Evaluation Criteria in Solid Tumors (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
• Eastern Cooperative Oncology Group (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 alanine aminotransferase (ALT) or aspartate aminotransferase (AST) up to 5 x upper limit of normal (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.

You may not qualify if:

• 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.
• 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.
• Human Immunodeficiency Virus (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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, Lee W, Yuan J, Wong P, Ho TS, Miller ML, Rekhtman N, Moreira AL, Ibrahim F, Bruggeman C, Gasmi B, Zappasodi R, Maeda Y, Sander C, Garon EB, Merghoub T, Wolchok JD, Schumacher TN, Chan TA. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015 Apr 3;348(6230):124-8. doi: 10.1126/science.aaa1348. Epub 2015 Mar 12.

  PMID: 25765070 BACKGROUND

• Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, Chen L, Sharfman WH, Anders RA, Taube JM, McMiller TL, Xu H, Korman AJ, Jure-Kunkel M, Agrawal S, McDonald D, Kollia GD, Gupta A, Wigginton JM, Sznol M. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012 Jun 28;366(26):2443-54. doi: 10.1056/NEJMoa1200690. Epub 2012 Jun 2.

  PMID: 22658127 BACKGROUND

• Lamarca A, Hubner RA, David Ryder W, Valle JW. Second-line chemotherapy in advanced biliary cancer: a systematic review. Ann Oncol. 2014 Dec;25(12):2328-2338. doi: 10.1093/annonc/mdu162. Epub 2014 Apr 25.

  PMID: 24769639 BACKGROUND

• Monge C, Pehrsson EC, Xie C, Duffy AG, Mabry D, Wood BJ, Kleiner DE, Steinberg SM, Figg WD, Redd B, Budhu A, Wang S, Tandon M, Ma L, Wei Wang X, Greten TF. A Phase II Study of Pembrolizumab in Combination with Capecitabine and Oxaliplatin with Molecular Profiling in Patients with Advanced Biliary Tract Carcinoma. Oncologist. 2022 Mar 11;27(3):e273-e285. doi: 10.1093/oncolo/oyab073.

  PMID: 35274717 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Biliary Tract Neoplasms; Cholangiocarcinoma; Bile Duct Neoplasms; Liver Neoplasms; Gallbladder Neoplasms

Interventions

pembrolizumab; Oxaliplatin; Capecitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Bile Duct Diseases; Liver Diseases; Gallbladder Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Dr. Tim F. Greten
• Organization: National Cancer Institute

tim.greten@nih.gov

240-760-6114

Study Officials

• Tim F Greten, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: National Cancer Institute

Study Record Dates

• First Submitted: April 12, 2017
• First Posted: April 13, 2017
• Study Start: June 14, 2017
• Primary Completion: July 22, 2020
• Study Completion: November 8, 2021
• Last Updated: December 3, 2021
• Results First Posted: April 15, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)