Study of the Antitumor Activity of Capecitabine in Combination With Erlotinib in Patients With Metastatic Colorectal Cancer

This study has been terminated.
(Study halted by drug manufacturer)
Sponsor:
Collaborators:
Hoffmann-La Roche
Genentech, Inc.
Information provided by:
Beth Israel Medical Center
ClinicalTrials.gov Identifier:
NCT00459901
First received: April 11, 2007
Last updated: January 20, 2011
Last verified: January 2011
  Purpose

To document the antitumor activity of capecitabine in combination with erlotinib in patients with previously untreated metastatic colorectal cancer. Time to tumor progression, objective response rate, time to confirmed response rate, duration of confirmed response rate, time to treatment failure, and CEA response will be assessed.


Condition Intervention Phase
Metastatic Colorectal Cancer
Drug: Erlotinib and capecitabine
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of OSI-774 (Erlotinib, Tarceva™,) and Capecitabine for Patients With Previously Untreated Metastatic Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by Beth Israel Medical Center:

Primary Outcome Measures:
  • To document the antitumor activity of capecitabine in combination with erlotinib in patients with previously untreated metastatic colorectal cancer [ Time Frame: Time to tumor progression, time to confirmed response rate, time to treatment failure, . ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To determine the qualitative and quantitative toxicity of this combination and sequence of drug administration [ Time Frame: Objective response rate, duration of confirmed response rate, CEA response will be assessed. ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 40
Study Start Date: June 2004
Study Completion Date: June 2005
Estimated Primary Completion Date: June 2005 (Final data collection date for primary outcome measure)
Detailed Description:

Approximately 150,000 people are diagnosed with colorectal cancer in the United States each year. Forty to fifty thousand people eventually will develop metastatic colorectal cancer and 40,000 people die annually because of advanced or metastatic colorectal cancer. Cancer patients prefer oral therapy over intravenous therapy as palliative treatment if efficacy regarding response rate and response duration is not compromised. Therefore, development of a completely oral combination therapy that approximates or improves upon the clinical outcomes attained by the reference triple drug therapies should be a research priority. Compared with intravenous 5-fluourouracil/leucovorin as first-line treatment for metastatic colorectal cancer, oral capecitabine has demonstrated similar survival outcomes (approximately 12-13 months), response rates (15-20%), and response durations (4-5 months) in two multi-institutional international randomized phase III trials. Erlotinib (OSI-774, Tarceva) is an orally available inhibitor of human EGFR tyrosine kinase. The epidermal growth factor receptor (EGFR) is overexpressed in a variety of human cancers including colorectal cancer. The principal goal of anticancer treatment with tyrosine kinase inhibitors such as erlotinib is to restore normal cellular growth by interrupting EGFR mediated cell proliferation and malignant The hypothesis of this phase II trial is that the unique mechanisms of action and non-overlapping toxicity profiles of capecitabine (Xeloda) and erlotinib will allow these drugs to be combined into a safe and tolerable regimen with better activity regarding response, response duration, and median survival than capecitabine alone in patients with previously untreated metastatic colorectal cancer.

  Eligibility

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

Inclusion Criteria:

  • Patients who have histologically or cytologically confirmed diagnosis of metastatic colorectal adenocarcinoma.
  • Patients must be > 18 years old.
  • Patients must have a performance status of > 60 on the Karnofsky scale
  • Patients must have an expected life expectancy of at least 12 weeks.
  • Patients must give written informed consent as per institutional and federal regulatory requirements.
  • Patients must have measurable or evaluable disease .
  • Patients must have an absolute neutrophil count of > 1,500/mm3 and a platelet count > 100,000/mm3.
  • Patients must have adequate liver and renal function defined by a bilirubin of < 2.0 mg/dl and a creatinine of < 1.5 mg/dl, respectively.
  • Patients must be able to stay in the general area for the duration of their treatment on this clinical research study.

Exclusion Criteria:

  • Prior chemotherapy, treatment with inhibitors of EGFR of any kind, molecularly targeted
  • Pregnant or lactating women
  • Clinical signs of brain involvement or leptomeningeal disease
  • Serious illness or medical conditions
  • Congestive heart failure or unstable angina pectoris, uncontrolled hypertension or arrhythmias
  • Active infections
  • UnstaOphthalmic disorders that might increase the risk for epithelium related complications (bullous keratopathy, aniridia, severe chemical burns, neutrophilic keratitis e.g.)
  • GI tract disease resulting in an inability to take oral medication such as uncontrolled inflammatory GI disease (e.g. Crohn's disease, ulcerative colitis) or post surgical malabsorption characterized by uncontrolled diarrhea that results in weight loss and vitamin deficiency orequires IV hyperalimentation (however, use of pancreatic enzyme supplementation is allowed provided that the above criteria are not met).
  • Prior invasive malignancies for less 5 years
  • Known to be HIV positive.
  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: NCT00459901

Locations
United States, New York
Beth Israel Medical Center
New York, New York, United States, 10003
Sponsors and Collaborators
Beth Israel Medical Center
Hoffmann-La Roche
Genentech, Inc.
Investigators
Principal Investigator: Peter Kozuch, MD Continuum Cancer Center
  More Information

Publications:
Responsible Party: Peter Kozuch, MD, Beth Israel Medical Center
ClinicalTrials.gov Identifier: NCT00459901     History of Changes
Other Study ID Numbers: 022-03, XEL308
Study First Received: April 11, 2007
Last Updated: January 20, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Beth Israel Medical Center:
Metastatic Colorectal Cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases
Capecitabine
Erlotinib
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014