Phase II study of pembrolizumab in metastatic biliary tract cancer as second-line treatment after failing to at least one cytotoxic chemotherapy regimen: integration of genomic analysis to identify predictive molecular subtypes
- Conditions
- Diseases of the digestive system
- Registration Number
- KCT0003948
- Lead Sponsor
- Samsung Medical Center
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 33
In order to be eligible for participation in this trial, the subject must:
1.Be willing and able to provide written informed consent/assent for the trial. The subject may also provide consent for Biomedical Research. However, the subject may participate in the main trial without participating in Biomedical Research.
2.Be ? 20 years of age on day of signing informed consent (or acceptable age according to local regulations, whichever is older).
3.Have histologically or cytologically-confirmed diagnosis of biliary tract cancer including intra- and extra-hepatic biliary tract cancer
4.Have metastatic disease or locally advanced, unresectable disease with feasible biopsy sites (baseline and follow up)
5.Has experienced documented objective radiographic or clinical disease progression during or after first-line therapy containing any platinum/gemcitabine or any platinum/ fluoropyrimidine doublet.
a.To be considered as second-line, the subject needs to have the documentation of disease progression on first-line treatment. The disease progression can be confirmed by CT scan or by clinical evidence (such as cytology report from newly developed ascites and plural effusion).
b.Any new or worsening malignant effusion (documented by ultrasound) may be confirmed by pathologic criteria (histology and/or cytology) if appropriate.
c.A subject experiencing clinical disease progression during or within 6 months following the last dose of adjuvant therapy will be eligible for enrollment provided they received any platinum/gemcitabine or any platinum/ fluoropyrimidine doublet as required.
d.To be eligible, the subject is required to have received at least one dose of any platinum/gemcitabine or any platinum/ fluoropyrimidine doublet therapy.
The dose reduction and discontinuation of one of these drugs, switching to/adding new drugs on the first-line treatment is allowed; however, the documentation of disease progression on/after the first-line treatment is required. Therefore, subjects with discontinuation due to adverse events on first-line treatment prior to disease progression are not eligible until disease progression is confirmed by documentation.
6.Have measurable disease based on mRECIST as determined by investigator. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
a.Note: The exact same image acquisition and processing parameters should be used throughout the study.
7.Be willing to provide fresh tissue for biomarker analysis, and, based on the adequacy of the tissue sample quality for assessment of biomarker status. Repeat samples may be required if adequate tissue is not provided. Newly obtained endoscopic biopsy specimens are preferred to archived samples and formalin-fixed, paraffin-embedded (FFPE) block specimens are preferred to slides.
a.Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen.
b.Collection of an archived tissue sample will also be requested (where available) to support evaluation of the clinical utility of biomarker assessment in newly obtained vs. archived tissue samples; however, a subject will not be precluded from participating in the study if an archived tissue sample is not available for collection or is otherwise insuffi
The subject must be excluded from participating in the trial if the subject:
1.Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
2.Has squamous cell or sarcomatoid biliary duct cancer. Ampulla of Vater cancer.
3.Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
4.Has a known history of active TB (Bacillus Tuberculosis)
5.Hypersensitivity to pembrolizumab or any of its excipients.
6.Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., = Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
7.Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., = Grade 1 or at baseline) from adverse events due to a previously administered agent.
-Note: Subjects with = Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
-Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
8.Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
9.Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
10.Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
11.Has known history of, or any evidence of interstitial lung disease or active, non-infectious pneumonitis.
12.Has an active infection requiring systemic therapy.
13.Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
14.Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
15.Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial tr
Study & Design
- Study Type
- Interventional Study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method objective response rate
- Secondary Outcome Measures
Name Time Method biomarker