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
18 Years
N/A
Both
Colorectal Cancer
Trial Information
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
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Number of patients that develop study drug related toxicity
Outcome Description:
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.
Outcome Time Frame:
3 courses (6 weeks)
Safety Issue:
Yes
Principal Investigator
Smitha Krishnamurthi, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
CASE2204
NCT ID:
NCT00118261
Start Date:
March 2005
Completion Date:
January 2011
Related Keywords:
- Colorectal Cancer
- stage IV rectal cancer
- stage IV colon cancer
- recurrent rectal cancer
- recurrent colon cancer
- Colorectal Neoplasms
Name | Location |
|---|---|
| MetroHealth Cancer Care Center at MetroHealth Medical Center | Cleveland, Ohio 44109 |
| Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center | Cleveland, Ohio 44106-5065 |
| UHHS Chagrin Highlands Medical Center | Orange Villager, Ohio 44122 |
