- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01828034
First Line Gemcitabine, Cisplatin and MEK162 in Advanced Biliary Tract Carcinoma
October 26, 2020 updated by: Memorial Sloan Kettering Cancer Center
A Phase I/II Study of First Line Gemcitabine, Cisplatin and MEK162 in Advanced Biliary Tract Carcinoma
The purpose of this study is to test an investigational combination of drugs for bile duct or gallbladder cancers.
Gemcitabine and cisplatin are two forms of chemotherapy commonly used in combination to treat bile duct and gallbladder cancers.
The investigators are looking to improve treatment results.
They will attempt to do so by adding the drug MEK162 to the treatment plan.
MEK162 acts by blocking a protein called MEK 1/2 which helps cancer cells grow and divide.
This study will help answer the question of whether MEK162 is a helpful drug in patients with bile duct or gallbladder cancers when given with gemcitabine and cisplatin.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
42
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
New York
-
New York, New York, United States, 10065
- Memorial Sloan Kettering Cancer Center
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Histologically / cytologically verified, non-resectable, recurrent, or metastatic biliary tract carcinoma including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma and gallbladder carcinoma. Combined cholangiocarcinoma and hepatocellular carcinoma is allowed.
- Patients must have measurable disease by RECIST 1.1
- KPS ≥ 80%
- Age ≥ 18 years
- Adequate bone marrow function defined as: Hb ≥ 8 g/dl, ANC ≥ 1.5 K/mcL, Platelets ≥ 100 K/mcL
- Adequate renal function defined as serum creatinine < 1.6 mg/dl and/or measured creatinine clearance from 24-hour urine collection of ≥ 60 ml/min
- Adequate hepatic function defined as total bilirubin ≤ 2 mg/dl, ALT/AST ≤ 5 x ULN.
- Patients with biliary obstruction can join if bilirubin corrects to required limit after adequate biliary drainage.
Adequate cardiac function defined as ejection fraction ≥ 45% as determined by transthoracic echocardiogram or MUGA
- Patients who have received prior local therapy, including but not limited to embolization, chemoembolization, radiofrequency ablation, radiation therapy, are eligible provided that measurable disease falls outside the treatment field or within the field but has shown an increase of ≥ 20% in the size. Prior local therapy must be completed at least 4 weeks prior to the baseline scan
- Women of childbearing potential must have a negative pregnancy test within 7 days prior to study treatment
- Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter.
- Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
- Any previous chemotherapy, biologic therapy, or investigational agent, except for adjuvant therapy as single agents and/or as radio-sensitizing agents limited to 5-fluorouracil and gemcitabine. Patient must have completed adjuvant therapy no less than six months prior to accrual.
- Evidence of another active cancer that may influence patient outcome as determined by the Principal Investigator (PI) or co-Principal Investigator (co-PI), except for nonmelanoma skin carcinoma, melanoma in-situ, in-situ carcinoma of the cervix curatively treated, treated superficial bladder cancer, and adenocarcinoma of the prostate that has been surgically treated with a post-treatment PSA that is non-detectable.
- Known brain metastases or primary central nervous system tumors with seizures that are not well controlled with standard medical therapy.
- Uncontrolled intercurrent illness including, but not limited to psychiatric illness/social situations that would limit compliance with study requirements.
- Known HIV positive patient
- Significant cardiovascular disease including congestive heart failure (New York Heart Association Class II or higher) or active angina pectoris.
- History of a myocardial infarction within 6 months.
- History of a stroke or transient ischemic attack within 6 months.
- Clinically significant peripheral vascular disease.
- Major surgical procedure within 4 weeks.
- Uncontrolled infection.
- Known or suspected allergy to gemcitabine or cisplatin
- Pregnant (positive pregnancy test)
- Breast-feeding should be discontinued if a nursing mother is to be treated on clinical trial.
- Any condition that impairs patient's ability to swallow whole pills
- Malabsorption problem that may limit or inhibit the absorption of MEK 162
- Patients with a history or current known evidence of central serous retinopathy (CSR), retinal vein occlusion (RVO) or ophthalmopathy at baseline that would be considered a risk factor for CSR or RVO.
- History of any organ or bone marrow transplant.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Gemcitabine, Cisplatin and MEK162
Phase I component of the study, a classic 3+3 cohort dose escalation scheme will be used to identify the MTD of MEK162 when administered with gemcitabine at dose 800 mg/m2 and cisplatin given at dose 20 mg/m2 week 2 & 3 of a 3 week cycle.
The final cohort will receive gemcitabine 1000mg/m2 and cisplatin 20mg/m2 week 2 and 3 of a 3 week cycle in combination with MEK162 at the MTD as determined above.
In the phase II part of the study, patients will receive MEK162 at the MTD dose plus gemcitabine and cisplatin at the dose level determined acceptable in the phase I portion.
In the phase II part of the study, patients will receive MEK162 at 45mg BID plus gemcitabine (800 mg/m2) and cisplatin (20 mg/m2) as determined by the phase I portion.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
MTD of MEK162 - Phase I
Time Frame: 1 year
|
In the phase I portion, up to 18 patients will be enrolled in classic 3+3 cohort dose escalation design to identify the MTD of MEK162 when administered with gemcitabine and cisplatin given weeks 2 and 3 of a 3 week cycle .
|
1 year
|
Six-month Progression Free Survival
Time Frame: 6 months
|
An exact binomial single stage design will be used to discriminate between true 6-month PFS rates of 59% vs. 82%, and between true response rates of 26% and 50%.
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
|
6 months
|
Objective Response Rate (ORR)
Time Frame: 1 year
|
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
|
1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Median PFS
Time Frame: 1 year
|
progression free survival will be calculated from study entry to documented disease progression or death from any cause, whatever occurs first.
|
1 year
|
Median Overall Survival
Time Frame: 1 year
|
(survival) will be calculated from study entry to death or last follow up
|
1 year
|
Participants Evaluated for Toxicity
Time Frame: 2 years
|
All toxicities will be rated as per the NCI Common Toxicity Criteria, version 4.
|
2 years
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
April 1, 2013
Primary Completion (Actual)
May 30, 2019
Study Completion (Actual)
May 30, 2019
Study Registration Dates
First Submitted
April 5, 2013
First Submitted That Met QC Criteria
April 5, 2013
First Posted (Estimate)
April 10, 2013
Study Record Updates
Last Update Posted (Actual)
November 17, 2020
Last Update Submitted That Met QC Criteria
October 26, 2020
Last Verified
June 1, 2019
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms, Glandular and Epithelial
- Carcinoma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Gemcitabine
- Cisplatin
Other Study ID Numbers
- 13-004
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Advanced Biliary Tract Carcinoma
-
First Affiliated Hospital of Zhejiang UniversityNot yet recruitingAdvanced Biliary Tract CarcinomaChina
-
GERCOR - Multidisciplinary Oncology Cooperative...AstraZenecaActive, not recruitingAdvanced Biliary Tract CarcinomaFrance
-
CSPC Ouyi Pharmaceutical Co., Ltd.Not yet recruitingIntrahepatic Cholangiocarcinoma | Gallbladder Carcinoma | Advanced Biliary Tract Cancer | Extrahepatic CholangiocarcinomaChina
-
RaND BiosciencesNot yet recruitingAdvanced Biliary Tract Cancer | Advanced Non-small-cell Lung Cancer
-
Zhejiang Cancer HospitalRecruitingAdvanced Biliary Tract TumorsChina
-
Samsung Medical CenterCompletedAdvanced Biliary Tract AdenocarcinomaKorea, Republic of
-
Shanghai Jiahui International HospitalShanghai Zhongshan HospitalRecruitingAdvanced Biliary Tract CarcinomaChina
-
ASLAN PharmaceuticalsCompletedAdvanced or Metastatic Solid Tumors | Advanced or Metastatic Biliary Tract CancerJapan
-
AIO-Studien-gGmbHServier; Institut für Klinisch-Onkologische Forschung der Krankenhaus Nordwest...Active, not recruitingBiliary Tract Cancer | Extrahepatic Bile Duct Carcinoma | Non-Resectable Hepatocellular Carcinoma | Adenocarcinoma Metastatic | Adenocarcinoma of the Biliary Tract | Adenocarinoma Locally Advanced | Intrahepatic Bile Duct CarcinomaGermany
-
Fudan UniversityRecruitingAdvanced Biliary Tract CancerChina
Clinical Trials on Gemcitabine
-
AstraZenecaRecruitingBiliary Tract CancerFrance, Spain, Italy, Korea, Republic of, Japan, Germany, United States, Singapore
-
Sierra Oncology LLC - a GSK companyCompletedAdvanced Solid TumorsSpain, United Kingdom
-
University of Erlangen-Nürnberg Medical SchoolCompleted
-
Shenzhen University General HospitalNot yet recruiting
-
3D Medicines (Sichuan) Co., Ltd.Not yet recruitingBiliary Tract Neoplasms
-
Kansai Hepatobiliary Oncology GroupCompleted
-
Fifth Affiliated Hospital, Sun Yat-Sen UniversityRecruiting
-
3D Medicines (Sichuan) Co., Ltd.RecruitingBiliary Tract NeoplasmsChina
-
Yung NAQueen Mary Hospital, Hong Kong; Pamela Youde Nethersole Eastern HospitalRecruitingMuscle-Invasive Bladder Carcinoma | Muscle Invasive Bladder Urothelial CarcinomaHong Kong
-
Air Force Military Medical University, ChinaRecruiting