Pembrolizumab, a Monoclonal Antibody Against PD-1, in Combination With

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

Not yet open.

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.

Condition Intervention Phase
Biliary Tract Cancer
Drug: Pembrolizumab (MK-3475)
Drug: Oxaliplatin
Drug: Capecitabine
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
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)

Resource links provided by NLM:

Drug Information available for: Oxaliplatin Capecitabine Pembrolizumab
Genetic and Rare Diseases Information Center resources: Biliary Tract Cancer
U.S. FDA Resources

Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
Median amount of time subject survives without disease progression for 5 month after treatment [ Time Frame: 5 Months ]

Secondary Outcome Measures:
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 ]

Estimated Enrollment: 19
Study Start Date: April 5, 2017
Estimated Study Completion Date: December 31, 2020
Estimated Primary Completion Date: December 31, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort
CAPOX and Pembrolizumab in BTC
Drug: 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
2000 mg/m^2 will be administered orally twice a day on Days 1-14 of cycles 1-6

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

Eligibility

Ages Eligible for Study: 18 Years to 99 Years (Adult, Senior)
Sexes Eligible for Study: All
Accepts Healthy Volunteers: No
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.
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
Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03111732

Contacts
Contact: Suzanne Fioravanti, R.N. (240) 760-6113 fioravas@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center Not yet recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office 888-624-1937
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Tim F Greten, M.D. National Cancer Institute (NCI)
More Information

Additional Information:
NIH Clinical Center Detailed Web Page This link exits the ClinicalTrials.gov site

Publications:
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.
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.
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):2328-38. doi: 10.1093/annonc/mdu162. Epub 2014 Apr 25. Review.

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT03111732 History of Changes
Other Study ID Numbers: 170082
17-C-0082
Study First Received: April 12, 2017
Last Updated: April 12, 2017

Keywords provided by National Institutes of Health Clinical Center (CC):
Immune-Based Strategies
Anti-PD1 Therapy
Chronic Inflammation
Combination Chemotherapy

Additional relevant MeSH terms:
Biliary Tract Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Biliary Tract Diseases
Digestive System Diseases
Antibodies
Antibodies, Monoclonal
Oxaliplatin
Pembrolizumab
Capecitabine
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 14, 2017

https://clinicaltrials.gov/ct2/show/NCT03111732