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Erlotinib, Modified FOLFOX6, and Bevacizumab as First-Line Therapy Metastatic Colorectal Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Smitha Krishnamurthi, Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00118261
First received: July 8, 2005
Last updated: August 31, 2012
Last verified: August 2012
  Purpose

RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as oxaliplatin, leucovorin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Erlotinib may help chemotherapy work better by making tumor cells more sensitive to the drugs. Giving erlotinib together with combination chemotherapy and bevacizumab may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of erlotinib when given together with combination chemotherapy and bevacizumab as first-line therapy in treating patients with metastatic colorectal cancer.


Condition Intervention Phase
Colorectal Cancer
Biological: bevacizumab
Drug: erlotinib hydrochloride
Drug: fluorouracil
Drug: leucovorin calcium
Drug: oxaliplatin
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase IB Study in Patients With Metastatic Colorectal Cancer to Evaluate Pharmacodynamic Effects of Erlotinib and Safety and Efficacy of Erlotinib in Combination With Modified FOLFOX6 (mFOLFOX6) and Bevacizumab

Resource links provided by NLM:


Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:
  • Number of patients that develop study drug related toxicity [ Time Frame: 3 courses (6 weeks) ] [ Designated as safety issue: Yes ]
    Dose-limiting toxicities will be tracked in the first three cycles. The occurrence of DLT in 2 of the first 6 patients, 3 of the first 9 patients, or 4 of the first 12 patients (whichever occurs soonest)will require that subsequent patients are enrolled to the study at 100 mg erlotinib daily.


Secondary Outcome Measures:
  • Patient Response to Treatment Measured by RECIST Criteria [ Time Frame: 3 courses (6 weeks) ] [ Designated as safety issue: No ]
    The overall response is the number of participants who experience a confirmed complete (CR) or partial response (PR) of the total analysis population. Per the Response Evaluation Criteria In Solid Tumors (RECIST): CR = all detectable tumor has disappeared, PR = a >=30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum, Progressive disease (PD) = a >=20% increase in target lesions, Stable Disease = small changes that do not meet previously given criteria.

  • Number of patients that can increase the erlotinib dose to 200mg [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
    The number of patients requiring an increase in erlotinib dose to 200 mg will be reported as well as the toxicities observed at 200 mg daily erlotinib, the median onset to grade 2 or higher rash and diarrhea at 200 mg erlotinib, and the number of patients requiring a decrease in erlotinib from 200 mg.


Enrollment: 17
Study Start Date: March 2005
Study Completion Date: January 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Erlotinib, modified FOLFOX6, and bevacizumab Biological: bevacizumab
Beginning in course 3, patients also receive bevacizumab IV over 30 minutes. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Drug: erlotinib hydrochloride
Courses 1-3: oral erlotinib once daily on days 1-14. Patients who do not develop grade 2 toxicity after the first 3 courses (6 weeks) will have their erlotinib dose escalated. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Drug: fluorouracil
Starting with course 2: fluorouracil IV continuously over 46 hours on days 1 and 2. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Drug: leucovorin calcium
Starting with course 2: Leucovorin calcium IV over 2 hours on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Drug: oxaliplatin
Starting with course 2: oxaliplatin IV over 2 hours on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Detailed Description:

OBJECTIVES:

  • Determine the toxicity of erlotinib, mFOLFOX6, and bevacizumab in patients with metastatic colorectal cancer.
  • Determine the efficacy of this regimen in these patients.
  • Determine the feasibility of escalating the dose of erlotinib in order to maximize the likelihood of developing a grade 2 skin rash in select patients.

OUTLINE: This is a multicenter study.

  • Single-agent erlotinib: Patients receive oral erlotinib once daily on days 1-14 (course 1).
  • Erlotinib, modified FOLFOX6, and bevacizumab chemotherapy: Patients receive oral erlotinib* once daily on days 1-14, oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV continuously over 46 hours on days 1 and 2 in course 2. Beginning in course 3, patients also receive bevacizumab IV over 30 minutes. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

NOTE: Patients who do not develop grade 2 toxicity after the first 3 courses (6 weeks) will have their erlotinib dose escalated.

PROJECTED ACCRUAL: A total of 22 patients will be accrued for this study.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed colorectal cancer

    • Biopsy-accessible metastatic disease
  • Measurable disease
  • No CNS metastases

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-2

Life expectancy

  • At least 3 months

Hematopoietic

  • WBC ≥ 4,000/mm^3 OR
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 10 g/dL
  • No bleeding disorder

Hepatic

  • Bilirubin ≤ 1.5 mg/dL
  • Albumin ≥ 2.5 g/dL

Renal

  • Creatinine ≤ 1.5 mg/dL
  • Urine protein:creatine ratio < 1.0

Cardiovascular

  • Blood pressure ≤ 150/100 mmHg
  • No arterial thrombotic event within the past 6 months
  • No New York Heart Association grade II-IV congestive heart failure

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 1 month after completion of study treatment
  • No other malignancy within the past 3 years except nonmelanoma skin cancer, carcinoma in situ of the cervix, or other malignancy with < 10% chance of relapse within 3 years
  • No uncontrolled infection
  • No severe uncontrolled illness that would preclude study participation
  • No peripheral neuropathy interfering with function
  • No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
  • No serious non-healing wound, ulcer, or bone fracture

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No concurrent immunotherapy
  • No concurrent sargramostim (GM-CSF)

Chemotherapy

  • No prior chemotherapy, including oxaliplatin, for metastatic disease
  • Prior adjuvant oxaliplatin allowed provided disease progressed > 12 months after completion of oxaliplatin
  • At least 3 weeks since prior cytotoxic chemotherapy (6 weeks for mitomycin or nitrosoureas)

    • No more than 2 courses of prior mitomycin
  • No concurrent chemotherapy

Endocrine therapy

  • No concurrent anticancer hormonal therapy

Radiotherapy

  • At least 2 weeks since prior radiotherapy
  • No prior radiotherapy to > 15% of bone marrow
  • No concurrent radiotherapy

Surgery

  • At least 4 weeks since prior major surgery
  • At least 1 week since prior minor surgery

Other

  • Recovered from prior therapy
  • No prior epidermal growth factor receptor inhibitor therapy
  • No other concurrent antineoplastic or antitumor therapy
  • No other concurrent investigational agents
  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: NCT00118261

Locations
United States, Ohio
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106-5065
MetroHealth Cancer Care Center at MetroHealth Medical Center
Cleveland, Ohio, United States, 44109
UHHS Chagrin Highlands Medical Center
Cleveland, Ohio, United States, 44122
Sponsors and Collaborators
Case Comprehensive Cancer Center
Investigators
Principal Investigator: Smitha Krishnamurthi, MD Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Smitha Krishnamurthi, Principal Investigator, Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00118261     History of Changes
Other Study ID Numbers: CASE2204, P30CA043703, CASE2204, NCI-2009-01287
Study First Received: July 8, 2005
Last Updated: August 31, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Case Comprehensive Cancer Center:
stage IV rectal cancer
stage IV colon cancer
recurrent rectal cancer
recurrent colon 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
Bevacizumab
Erlotinib
Fluorouracil
Levoleucovorin
Oxaliplatin
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antidotes
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 24, 2014