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Erlotinib and Chemotherapy for 2nd Line Treatment (Tx) of Metastatic Colorectal Cancer (mCRC)

This study has been terminated.
(Terminated due to poor enrollment and grade 3 toxicities noted during an interim analysis.)
Sponsor:
Collaborators:
Genentech, Inc.
OSI Pharmaceuticals
Information provided by (Responsible Party):
OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier:
NCT00642746
First received: March 24, 2008
Last updated: September 24, 2014
Last verified: September 2014
  Purpose

The purpose of this study is to see if alternating chemotherapy with erlotinib increases tumor shrinkage in people with metastatic colorectal cancer. The investigator will also be studying the side effects (good and bad) of alternating chemotherapy with erlotinib on metastatic colorectal cancer.


Condition Intervention Phase
Metastatic Colorectal Cancer
Drug: Erlotinib
Drug: Fluorouracil
Drug: Leucovorin
Drug: Oxaliplatin
Drug: Irinotecan
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Erlotinib (Tarceva) Alternating With Chemotherapy for Second-line Treatment of Metastatic Colorectal Cancer With Molecular Correlates for p53 Pathway

Resource links provided by NLM:


Further study details as provided by OHSU Knight Cancer Institute:

Primary Outcome Measures:
  • Response Rates of Radiographically Measurable Disease [ Time Frame: Disease response assessed after every 2 Treatment Cycles, or around 8 weeks. ] [ Designated as safety issue: No ]
    The primary outcome measure will be the response rates of radiographically measurable disease. Response rate of disease will be assessed per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT scan: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >= 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), >= 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease.


Secondary Outcome Measures:
  • Second-line Progression Free Survival [ Time Frame: Upon completion of follow-up, for an average of 99 days following the initiation of study treatment. ] [ Designated as safety issue: No ]
    Time to disease progression from start of second-line experimental regimen. Disease progression will be measured per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT scan: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >= 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), >= 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease.

  • Time to Second Progression (From Start of First-Line Regimen) [ Time Frame: Documented by Follow-up CT scans following first line treatment, average of 225 days. ] [ Designated as safety issue: No ]

    Number of days from the initiation of first line treatment to first documented progression. Progression will be assessed per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT scan: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >= 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), >= 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease.

    Progression free survival (time to progression or death, whichever occurs first) is the same as time to progression as all of the patients in this trial progressed.



Enrollment: 16
Study Start Date: March 2008
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: FOLFOX with Erlotinib
Subjects received FOLFOX (Leucovorin, Fluorouracil, and Oxaliplatin) and Erlotinib. Treatment consisted of a 28 day cycle. Subjects received FOLFOX on days 1, 2, and 3, and 15-16, followed by Erlotinib on days 3-8, and 17-22.
Drug: Erlotinib

Erlotinib oral tablets are conventional, immediate-release tablets containing erlotinib as the hydrochloride salt. In addition to the active ingredient, erlotinib contains lactose (hydrous), microcrystalline cellulose, sodium starch glycolate, sodium lauryl sulfate, and magnesium stearate.

Tablets containing 25 mg, 100 mg, and 150 mg of erlotinib are available. Each bottle will contain 30 tablets, a quantity sufficient for 4 consecutive weeks of dosing, with overage.

Other Name: Tarceva
Drug: Fluorouracil
Antimetabolite used as a chemotherapy. Administered intravenously as a bolus injection at 400mg/m2 on Day 1 followed by 2400 mg/m2 continuously over 46 hours.
Drug: Leucovorin
Chemotherapy agent given as a supplement to Fluorouracil. Given intravenously 400mg/m2 in combination with Fluorouracil dosing.
Drug: Oxaliplatin
Platinum-based antineoplastic chemotherapy agent given intravenously at 85 mg/m2.
Experimental: FOLFIRI with Erlotinib
Subjects received FOLFIRI (Leucovorin, Fluorouracil, and Irinotecan) and Erlotinib. Treatment consisted of a 28 day cycle. Subjects received FOLFIRI on days 1, 2, and 3, and 15-16, followed by Erlotinib on days 3-8, and 17-22.
Drug: Erlotinib

Erlotinib oral tablets are conventional, immediate-release tablets containing erlotinib as the hydrochloride salt. In addition to the active ingredient, erlotinib contains lactose (hydrous), microcrystalline cellulose, sodium starch glycolate, sodium lauryl sulfate, and magnesium stearate.

Tablets containing 25 mg, 100 mg, and 150 mg of erlotinib are available. Each bottle will contain 30 tablets, a quantity sufficient for 4 consecutive weeks of dosing, with overage.

Other Name: Tarceva
Drug: Fluorouracil
Antimetabolite used as a chemotherapy. Administered intravenously as a bolus injection at 400mg/m2 on Day 1 followed by 2400 mg/m2 continuously over 46 hours.
Drug: Leucovorin
Chemotherapy agent given as a supplement to Fluorouracil. Given intravenously 400mg/m2 in combination with Fluorouracil dosing.
Drug: Irinotecan
Chemotherapy agent given intravenously at 180 mg/m2.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patients must fulfill all of the following criteria to be eligible for study entry:

  • Age 18-80
  • Able to provide informed consent
  • Biopsy proven unresectable metastatic adenocarcinoma of the colon or rectum
  • Documented progression on prior first-line oxaliplatin-based or irinotecan-based regimen for metastatic colorectal cancer
  • Radiographically measurable disease with at least one bidimensionally measurable lesion of > 1 cm
  • Prior first-line regimen must have been completed at least 4 weeks prior to study treatment
  • Use of biologic agents with first-line chemotherapy permitted
  • Previous adjuvant regimens must have been greater than 6 months before inclusion
  • Adequate organ function including bone marrow, liver and renal function as defined by the following values: absolute neutrophil count > 1500/microliter; Hgb > 9 g/dL; platelets > 90,000/microliter; International Normalized Ratio < 1.8 (unless in therapeutic range if taking warfarin or other warfarin-derivative anticoagulants and are being monitored regularly for changes in prothrombin time or International Normalized Ratio); bilirubin < 2 times the Upper Limit of Normal; alkaline phosphatase < 3 times the Upper Limit of Normal; aspartate aminotransferase/alanine aminotransferase < 5 times the Upper Limit of Normal; serum creatinine < 1.5 times the Upper Limit of Normal
  • Eastern Cooperative Oncology Group status < 2

Exclusion Criteria:

Patients meeting any of the following criteria are ineligible for study entry:

  • Prior second-line chemotherapy regimens for colorectal cancer
  • Prior treatment with erlotinib or gefitinib
  • Central Nervous System metastasis
  • Second malignancies less than 5 years prior to enrollment. Completely resected basal or squamous cell carcinoma of the skin is allowed.
  • Untreated/unresolved bowel obstruction
  • Inability to take oral mediations
  • HIV positive
  • Pregnancy
  • Other uncontrolled medical illnesses
  • Current diarrhea > grade 2
  • Symptomatic angina or uncontrolled congestive heart failure
  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: NCT00642746

Locations
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
Sponsors and Collaborators
OHSU Knight Cancer Institute
Genentech, Inc.
OSI Pharmaceuticals
  More Information

No publications provided

Responsible Party: OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier: NCT00642746     History of Changes
Other Study ID Numbers: 3753
Study First Received: March 24, 2008
Results First Received: February 12, 2014
Last Updated: September 24, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by OHSU Knight Cancer Institute:
Colon
Cancer
Metastatic
Colorectal

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
Erlotinib
Fluorouracil
Irinotecan
Oxaliplatin
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protein Kinase Inhibitors
Radiation-Sensitizing Agents
Therapeutic Uses
Topoisomerase I Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on November 20, 2014