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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


Phase 1
18 Years
N/A
Not Enrolling
Both
Colorectal Cancer

Thank you

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 CenterCleveland, Ohio  44109
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer CenterCleveland, Ohio  44106-5065
UHHS Chagrin Highlands Medical CenterOrange Villager, Ohio  44122