First Line Gemcitabine, Cisplatin and MEK162 in Advanced Biliary Tract Carcinoma

NCT01828034 | Completed Phase 1 Results

• 1 other identifier: 13-004
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Advanced Biliary Tract Carcinoma

Keywords

Gemcitabine; Cisplatin; MEK162; 13-004

Outcome Measures

Primary Outcomes (3)

• MTD of MEK162 - Phase I

  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

  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)

  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 Outcomes (3)

• Median PFS

  1 year

• Median Overall Survival

  1 year

• Participants Evaluated for Toxicity

  2 years

Study Arms (1)

Gemcitabine, Cisplatin and MEK162

EXPERIMENTAL

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.

Drug: Gemcitabine; Drug: Cisplatin; Drug: MEK162

Interventions

Gemcitabine DRUG

Gemcitabine, Cisplatin and MEK162

Cisplatin DRUG

Gemcitabine, Cisplatin and MEK162

MEK162 DRUG

Gemcitabine, Cisplatin and MEK162

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Array BioPharma: collaborator

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Interventions

Gemcitabine; Cisplatin; binimetinib

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Results Point of Contact

• Title: Dr. Ghassan Abou-Alfa, MD
• Organization: Memorial Sloan Kettering Cancer Center

abou-alg@mskcc.org

646-888-4184

Study Officials

• Ghassan Abou-Alfa, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 5, 2013
• First Posted: April 10, 2013
• Study Start: April 1, 2013
• Primary Completion: May 30, 2019
• Study Completion: May 30, 2019
• Last Updated: November 17, 2020
• Results First Posted: November 17, 2020

Record last verified: 2019-06

Locations

US (1)