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Biliary Tract NeoplasmsPhase 2NCT03111732

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

A Phase 2 study testing Pembrolizumab (MK-3475), Oxaliplatin and Capecitabine in people with Biliary Tract Neoplasms and Cholangiocarcinoma, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Pembrolizumab (MK-3475), Oxaliplatin and Capecitabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
1 siteUnited States
Study dates
14 Jun 2017to 8 Nov 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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.
  • 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.

Who cannot join

  • 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.
Show all 19Show fewer
  • 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.
  • 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.
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20892

Other trials in United States

About this study

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)

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.

Read more

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.

Read the 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

Being tested
Pembrolizumab (MK-3475), Oxaliplatin, Capecitabine
Keywords
Immune-Based Strategies, Anti-PD1 Therapy, Chronic Inflammation, Combination Chemotherapy
Medical subject headings
Biliary Tract Neoplasms, Cholangiocarcinoma, Bile Duct Neoplasms, Liver Neoplasms, Gallbladder Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Pembrolizumab (MK-3475)Biological

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

  • OxaliplatinDrug

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

  • CapecitabineDrug

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

Study groups in NCT03111732
Study groupRoleWhat they receive
1/Arm 1ExperimentalPembrolizumab plus Oxaliplatin plus Capecitabine
Receives: Biological: Pembrolizumab (MK-3475); Drug: Oxaliplatin; Drug: Capecitabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 5 Months

Secondary outcomes (5)

  1. Number of Participants Obtaining a Complete Response (CR) and Partial Response (PR)

    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.

    Measured: Every 9 Weeks, until disease progression or patient is taken off the trial, whichever comes first, approximately 36 weeks.

  2. Overall Survival

    Median amount of time subject survives after therapy.

    Measured: Death, approximately 48 weeks after stopping therapy.

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

    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).

    Measured: 30 Days After Enrollment

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

    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).

    Measured: 30 Days After Enrollment

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

    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).

    Measured: 30 Days After Enrollment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Apr 2017
  2. Study start14 Jun 2017
  3. Primary completion22 Jul 2020
  4. Study completion8 Nov 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03111732
Sponsor's protocol ID
170082
Other IDs
17-C-0082
Status last verified
Dec 2021
First submitted
12 Apr 2017
Last updated
3 Dec 2021
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

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.

    PubMed 25765070

  • 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.

    PubMed 22658127

  • 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.

    PubMed 24769639

  • 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.

    PubMed 35274717

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pembrolizumab (MK-3475), Oxaliplatin and Capecitabine in people with Biliary Tract Neoplasms and Cholangiocarcinoma, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Apr 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival (PFS) (time frame: 5 Months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03111732, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Dec 2021.

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