Brief Title
Study of PD-1 Inhibitor in Combination With Gemcitabine/Cisplatin for Advancer BTCs
Official Title
A Pilot Study of PD-1 Inhibitor in Combination With Gemcitabine/Cisplatin for Patients With Advanced Unresectable or Metastatic Biliary Tract Cancers
Brief Summary
This is a single-arm, phase I/II trial in biliary tract cancer (BTC) patients. The purpose of
this trial is to evaluate the safety and effect of PD-1 inhibitor in combination with
gemcitabine/cisplatin chemotherapy in patients with advanced unresectable or metastatic BTCs.
The primary objective: 6-month progression free survival (PFS). The second objectives:
objective clinical response(according to RECIST version 1.1), safety, symptom control and
quality of life (QoL) (according to EORTC QoL C30 and BIL 21), overall survival. The
exploratory objectives: assessment of immunological response (cytokines, lymphocyte
phenotype, immunoglobulins), and evaluation of pathological, immunological and clinical
predictive factors for response/toxicity.
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
The percentage of patients alive and without progression at 6 months
Secondary Outcome
The percentage of patients that respond to combination treatment
Condition
Biliary Tract Cancer
Intervention
PD-1 inhibitor + Gemcitabine + Cisplatin
Study Arms / Comparison Groups
PD-1 inhibitor + Gemcitabine+Cisplatin
Description: Patients will be enrolled in the experimental arm and will receive Gemcitabine on day 1 and 5 (1000mg/m2 ) +Cisplatin on day 1(75mg/m2)+ PD-1 inhibitor on day 3 (Nivolumab 3mg/kg, or SHR-1210 200mg) every 3 weeks. If there is continued benefit after 6 months, PD-1 inhibitor will be administered as maintenance treatment until tumor progression or death.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
30
Start Date
May 1, 2017
Completion Date
October 2019
Primary Completion Date
October 2018
Eligibility Criteria
Inclusion Criteria:
- Age≥18 years with estimated life expectancy >3 months.
- Histopathological/cytological diagnosis of unresectable or recurrent / metastatic
biliary tract carcinoma (intra-hepatic, extrahepatic or gall bladder) and had at least
one measurable disease (≥1cm) by CT or MRI.
- Patients should provide samples of tumor tissue biopsied or resected no more than 3
months before enrollment and be willing to accept biopsy in the process of the study.
- Patients may have received prior radiotherapy,chemotherapy,or other local ablative
therapies, which completed ≥ 4 weeks prior to registration AND patient has recovered
to <= grade 1 toxicity.
- ECOG (Eastern Cooperative Oncology Group) performance status of 0-2.
- Adequate organ and marrow function obtained ≤ 2 weeks prior to registration as defined
below:
leukocytes greater than or equal to 3.0 x 10^9/L absolute neutrophil count greater than or
equal to 1.0 x 10^9/L platelets greater than or equal to 100 x 10^9/L hemoglobin greater
than or equal to 90 g/L total bilirubin less than or equal to 2 xULN serum albumin should
be no less than 25g/L ALT or AST less than 2 xULN serum creatinine less than 1.5 x ULN
- Ability to understand and willingness to sign a written informed consent document.
- 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, and up
to 120 days after the last dose of the drug.
Exclusion Criteria:
- Active, known or suspected autoimmune diseases.
- Known brain metastases or active central nervous system (CNS). If patients with CNS
metastases were treated with radiotherapy for at least 3 months prior to enrollment
and have no central nervous symptoms and are off corticosteroids, they will be
eligible but will need a Brain MRI prior to enrollment.
- Participants are being treated with either corticosteroids (>10 mg daily prednisone
equivalent) or other immunosuppressive medications within 14 days of enrollment.
- Prior therapy with anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody (including
ipilimumab or any other antibody specifically targeting T-cell costimulation or
checkpoint pathways).
- History of severe hypersensitive reactions to other monoclonal antibodies.
- History of allergy or intolerance to study drug components.
- Substance abuse, medical, psychological or social conditions that may interfere with
the patient's participation in the study or evaluation of the study results.
- History or concurrent condition of interstitial lung disease of any grade or severely
impaired pulmonary function.
- Uncontrolled intercurrent illness including 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 and any other illness that would limit compliance with study
requirements and jeopardize the safety of the patient.
- History of human immunodeficiency virus (HIV) infection or acquired immunodeficiency
syndrome (AIDS).
- Pregnant or breast-feeding patients. Women of childbearing potential must have a
pregnancy test performed within 7 days before the enrollment, and a negative result
must be documented.
- Previous or concurrent cancer within 3 years prior to treatment start EXCEPT for
curatively treated cervical cancer in situ, non-melanoma skin cancer, superficial
bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades
lamina propria)].
- Vaccination within 30 days of study enrollment.
- Active bleeding or known hemorrhagic tendency.
- Patients with unhealed surgical wounds for more than 30 days.
- Being participating any other trials or withdraw within 4 weeks.
Gender
All
Ages
18 Years - 75 Years
Accepts Healthy Volunteers
No
Contacts
Weidong Han, Ph.D, +86-10-66937463, [email protected]
Location Countries
China
Location Countries
China
Administrative Informations
NCT ID
NCT03311789
Organization ID
CHN-PLAGH-BT-024
Responsible Party
Principal Investigator
Study Sponsor
Chinese PLA General Hospital
Study Sponsor
Weidong Han, Ph.D, Study Director, Department of Biotherapeutic, Chinese PLA General Hospital
Verification Date
October 2017