This is the classic website, which will be retired eventually. Please visit the modernized ClinicalTrials.gov instead.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Durvalumab(MEDI4736)/Tremelimumab in Combination With Gemcitabine/Cisplatin in Chemotherapy-naïve Biliary Tract Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03046862
Recruitment Status : Active, not recruiting
First Posted : February 8, 2017
Last Update Posted : April 19, 2024
Sponsor:
Information provided by (Responsible Party):
Do-Youn Oh, Seoul National University Hospital

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:

<Research Hypothesis> The dynamics of immune systems by cytotoxic chemotherapy and its changes by combination with immuno-oncology agents will be uncovered.

The combination of Durvalumab/Tremelimumab with gemcitabine/cisplatin chemotherapy is feasible and efficacious in chemo-naïve biliary tract cancer.

<Purpose of the study> To assess the effect of Durvalumab/Tremelimumab in combination with gemcitabine/cisplatin on response rate (RR) in chemo-naïve advanced biliary tract cancer patients.


Condition or disease Intervention/treatment Phase
Biliary Tract Neoplasms Drug: Durvalumab Drug: Tremelimumab Drug: Gemcitabine Drug: Cisplatin Phase 2

Detailed Description:

<Rationale for conducting this study>

  1. Rational #1. The incidence of biliary tract cancer (BTC) is higher in Korea than the West. (Korea: 10 new cases/100,000 population every year, the West:1-2 cases/100,100 population every year). Therefore, to conduct clinical study of BTC in Korea is very feasible and efficient.
  2. Rational #2 The Gemcitabine/cisplatin is the current standard of care in 1st-line treatment for advanced BTC ((N Engl J Med 2010; 362 (14): 1273-81). No one-targeted therapy has been approved in BTC, yet. The overall survival of advanced BTC with cytotoxic chemotherapy is only 8-10 months, in general. Therefore, there is a huge unmet medical need.
  3. Rational #3 In recent sequencing data of BTC showed the BTC patients with the worse prognosis had significant enrichment of hypermutated tumors and a characteristic elevation in the expression of immune checkpoint molecules. According, immune-modulating therapies also be potentially promising options for these patients (Nat Genet. 2015 Sep;47(9):1003-10.)
  4. Rational #4 In PDL1 (+) BTC, anti-PD1 Ab shows promising activity as a monotherapy (Bang YJ, et al. ECC/ESMO 2015) In one clinical study of pembrolizumab, 37 out of 89 BTC patients (41.6%) showed the PDL1 (+) tumor. Among 24 PDL1 (+) patients who were enrolled and treated with pembrolizumab, 50% were Asian, 62.5% had ECOG 1, 16.7% had gallbladder cancer, 80% were at the 3rd-line or later setting. Four patients showed PR (3 from Seoul National University Hospital), 4 patients SD, which led the overall response rate of 17.4%. A total 40% of patients showed tumor shrinkage. The decreases in tumor size were generally maintained over time. This study gives us the evidence that immune checkpoint inhibitor is working on BTC likewise other solid tumors.
  5. Rational #5 In recent studies have shown the combination of CTLA4 inhibitor with anti-PD1/PDL1 agents shows the enhanced clinical activities, especially, regardless of PDL1 status. This combination strategy is being actively under test in many solid tumors.

  6. Rational #6 Certain chemotherapeutic drugs stimulate cancer-specific immune responses by inducing immunogenic cell death and other effector mechanisms (Immunity 2013, Annu Rev Immunol 2013) With the cytotoxic chemotherapy, the PDL-1 is induced and this increased expression of PDL1 contributes the resistance to cytotoxic chemotherapy. Successful eradication of tumors by immunogenic chemotherapy requires removal of immunosuppressive IgA+, PDL1+plasmocytes (Nature 2015). More importantly, still vast majorities of dynamic changes of immune system by cytotoxic chemotherapy are unanswered.

    These support that the combination of cytotoxic chemotherapy with immuno-oncology agents including immune checkpoint inhibitors might be efficacious and needed.

  7. Rational #7 The advantages of "Immunotherapy and cytotoxic chemotherapy" combination are; 1) can explore science on the dynamic immunologic changes by cytotoxic chemotherapy and its overcome by immunotherapy 2) easy way to be incorporated in the current clinical practice 3) can be applied to variety of tumor types such as NSCLC, urothelial cancer. 4) relatively affordable than "immunotherapy and targeted agent" combination. Durvalumab/Tremelimumab in combination of cytotoxic chemotherapy has not been tested, especially in BTC.

<Sample Size Determination> Primary efficacy endpoint is response rate. In BTC, the response rate of 1st-line gemcitabine/cisplatin chemotherapy is about 20% (20% in BT22 clinical trial, 25% in ABC-02 clinical trial). Therefore, we set H0 as 20%, and H1 as 40%. Using 75% of power and a-error of 0.05, a total 28 patients will be needed. When we assume the drop-out rate of 10%, a total of 31 patients will be enrolled.

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 31 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Biomarker-oriented Study of Durvalumab(MEDI4736)/Tremelimumab in Combination With Gemcitabine/Cisplatin in Chemotherapy-naïve Biliary Tract Cancer
Actual Study Start Date : February 25, 2017
Actual Primary Completion Date : May 30, 2020
Estimated Study Completion Date : December 31, 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: Durvalumab/Tremelimumab+chemotherapy
Durvalumab and Tremelimumab in combination with gemcitabine/cisplatin.
 Drug: Durvalumab
Durvalumab 1.12 g iv on D1 every 3 weeks
Other Name: MEDI4736

Drug: Tremelimumab
Tremelimumab 75mg iv on D1 every 3 weeks

Drug: Gemcitabine
Gemcitabine 1000 mg/m2 iv on D1& D8 every 3 weeks

Drug: Cisplatin
Cisplatin 25 mg/m2 iv on D1& D8 every 3 weeks


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Response rate [ Time Frame: 6 weeks ]
    According to RECIST v1.1 criteria


Secondary Outcome Measures :
  1. Disease control rate [ Time Frame: 6 weeks ]
    the percentage of patients who have achieved complete response, partial response and stable disease

  2. Progression-free survival [ Time Frame: 6 weeks ]
    Time from randomization until disease progression or death

  3. Duration of response [ Time Frame: 1 year ]
    Time from documentation of tumor response to disease progression

  4. Overall survival [ Time Frame: 1 year ]
    Time from randomization until death from any cause

  5. Quality-of-life as measured by EORTC QLQ-BIL21 [ Time Frame: 1 year ]
    EORTC QLQ-BIL21

  6. Overall response rate [ Time Frame: 6 week ]
    According to immune-related response criteria

  7. Safety and tolerability as measured by number and grade of toxicity events [ Time Frame: 6 week ]
    CTCAE V4.1


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically proven BTC, including intrahepatic cholangiocarcinoma, extrahepatic bile duct cancer, gallbladder cancer, ampulla of vater cancer
  • Unresectable or recurrent
  • chemotherapy -naïve for their unresectable or recurrent cancer (Previous expose to adjuvant chemotherapy is allowed)
  • should have measurable lesion
  • ECOG 0, 1
  • Without previous expose to immune-oncology agents including anti-CTLA4, anti-PD1, anti-PDL1, etc

  • Adequate organ function

    : ANC>1500/mm3, platelet>100K/mm3, HgB>9 g/Dl, bilirubin<1.5 x ULN, ALT/AST<2.5 X UNL, (in case of liver metastasis, <5 Xunl), Cr<1.5 mg/Dl

  • Informed consent

Exclusion Criteria:

  • Previous treatment for unresectable or recurrent cancer
  • Under immunosuppressive agents higher than equivalent dose of prednisone 10mg/day
  • Uncontrolled disease such as current active infection, congestive heart failure, uncontrolled hypertension, unstable angina, arrhythmia, interstitial lung disease
  • Current active pulmonary tuberculosis
  • Current active hepatitis B or hepatitis C (simple carrier is allowed)
  • anti-HIV (+)
  • Pregnant, breast-feeding women
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03046862


Locations
Layout table for location information
Korea, Republic of
Seoul National University Hospital
Seoul, Korea, Republic of, 110-744
Sponsors and Collaborators
Seoul National University Hospital
Investigators
Layout table for investigator information
Principal Investigator: Do-Youn Oh, MD, PhD Seoul National University Hospital
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Layout table for additonal information
Responsible Party: Do-Youn Oh, Professor, Seoul National University Hospital
ClinicalTrials.gov Identifier: NCT03046862    
Other Study ID Numbers: BTC-1st MEDITREME
First Posted: February 8, 2017    Key Record Dates
Last Update Posted: April 19, 2024
Last Verified: April 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Biliary Tract Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Biliary Tract Diseases
Digestive System Diseases
Gemcitabine
 Durvalumab
Tremelimumab
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological