Gemcitabine and Cisplatin Plus Sorafenib in Patients With Advanced Biliary Tract Carcinomas Naive to Systemic Therapy

This study has been completed.
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00919061
First received: June 11, 2009
Last updated: March 12, 2014
Last verified: March 2014
  Purpose

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. We are looking to improve treatment results. We will attempt to do so by adding sorafenib (a type of monoclonal antibody) to your treatment plan. Sorafenib acts by attaching to blocking specific targets on cells. These targets may help the cancer cells grow and divide. This study will help answer the question of whether sorafenib is a helpful drug in patients with bile duct or gallbladder cancers when given with gemcitabine and cisplatin.

This study is a phase 2 study. The purpose of a phase 2 study is to find out what effects, good and/or bad, sorafenib in combination with gemcitabine and cisplatin has on advanced bile duct and gallbladder cancers.


Condition Intervention Phase
Extrahepatic Bile Duct Cancer
Gallbladder Cancer
Drug: Gemcitabine and Cisplatin plus Sorafenib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Gemcitabine and Cisplatin Plus Sorafenib in Patients With Advanced Biliary Tract Carcinomas Naïve to Systemic Therapy

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • To determine the 6 month progression-free survival rate for patients with advanced biliary tract carcinomas treated with gemcitabine and cisplatin plus sorafenib. [ Time Frame: the six months CTscan can occur anytime within two weeks before or two weeks after the 6 months mark ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To determine the toxicity profile, radiologic response rate, and associated time to progression and overall survival. [ Time Frame: toxicity assessment week 1 & 2 then every cycle, Re-staging imaging studies will be obtained every 3 cycles. ] [ Designated as safety issue: Yes ]
  • To correlate, progression-free survival, response, time to progression and overall survival with pre-treatment tumor-cell pERK expression. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment: 39
Study Start Date: August 2009
Study Completion Date: March 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Gemcitabine and Cisplatin plus Sorafenib
This is a non-randomized, open label, single institution, phase II study of gemcitabine and cisplatin plus sorafenib for the treatment of patients with advanced or biliary tract carcinomas naïve to systemic therapy.
Drug: Gemcitabine and Cisplatin plus Sorafenib

Patients will receive treatment under the following schedule:

Gemcitabine: 800 mg/m2 over 30 minutes IV, weekly for 2 weeks, followed by a week off treatment.

Cisplatin: 20 mg /m2 over 30 minutes IV, weekly for 2 weeks, followed by a week off treatment.

Sorafenib: 400 mg PO once a day continuously. Three weeks of treatment correspond to one cycle.


  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 uni-dimensionally measurable disease by x-ray, CT scan, MRI scan or physical examination.
  • 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 < 2.0 mg/dl and calculated creatinine clearance ≥ 60 ml/min using the formula:
  • Cockcroft-Gault formula:

Cockcroft-Gault Formula - MALES CrCl = (140 - age[years]) (body wt[kg]) (72) (serum creatinine [mg/dL]) Cockcroft-Gault Formula - FEMALES CrCl = 0.85 x male value

  • If calculated creatinine clearance is not within range using the above formula, then measured levels from 24-hour urine collection may be used to calculate the creatinine clearance.
  • Adequate hepatic function defined as total bilirubin ≤ 2 mg/dl, ALT/AST/ ≤ 3 x ULN (≤ 5 if liver metastases). Patients with biliary obstruction can join if bilirubin corrects to required limit after adequate biliary drainage.
  • PT/INR ≤ 1.7 and PTT ≤ 1.5 x ULN, unless the patient is receiving anti-coagulation therapy with agents such as warfarin or heparin
  • Patients who have received prior local therapy, i.e. embolization, radiation therapy, etc. (except for chemoembolization) 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.
  • 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. Patients are encouraged to continue barrier method contraception for two years or longer after treatment.
  • 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 5-FU or gemcitabine given as adjuvant therapy as single agents and/or as radio-sensitizing agents. Patient must have completed adjuvant therapy no less than six months prior to accrual. Patients with previous significant allergic hypersensitivity to gemcitabine are excluded.
  • Evidence of another active cancer that may influence patient outcome as determined by the Principal Investigator, except for non-melanoma 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
  • History of primary central nervous system tumors or brain metastases, and/or seizures 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
  • Blood Pressure of > 150/100 mm Hg
  • 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.
  • Evidence of bleeding diathesis or coagulopathy.
  • Major surgical procedure, open biopsy, or significant traumatic injury within 4 weeks.
  • Uncontrolled infection.
  • Known or suspected allergy to sorafenib or any agent given in the course of this trial.
  • Pregnant (positive pregnancy test)
  • Breast-feeding should be discontinued if the mother is to be treated on clinical trial.
  • Serious non-healing wound, ulcer, or bone fracture
  • Use of St. John's Wort or rifampin (rifampicin)
  • Any condition that impairs patient's ability to swallow whole pills
  • Any malabsorption problem
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00919061

Locations
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Bayer
Investigators
Principal Investigator: Ghassan Abou-Alfa, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00919061     History of Changes
Other Study ID Numbers: 09-029
Study First Received: June 11, 2009
Last Updated: March 12, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
GALL BLADDER
BILE DUCTS
BAY 43-9006
SORAFENIB
CISPLATIN
GEMCITABINE
09-029

Additional relevant MeSH terms:
Bile Duct Neoplasms
Biliary Tract Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Bile Duct Diseases
Biliary Tract Diseases
Digestive System Diseases
Gemcitabine
Sorafenib
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on September 22, 2014