A Pilot Clinical Trial of Preoperative Cetuximab With Concurrent Continuous Infusion Fluorouracil and Pelvic Radiation in Patients With Local-Regionally Advanced Rectal Cancer
18 Years
N/A
Both
Colorectal Cancer
Trial Information
A Pilot Clinical Trial of Preoperative Cetuximab With Concurrent Continuous Infusion Fluorouracil and Pelvic Radiation in Patients With Local-Regionally Advanced Rectal Cancer
OBJECTIVES:
Primary
- Determine the safety profile of neoadjuvant cetuximab, fluorouracil, and pelvic
irradiation in patients with locally advanced or locally recurrent rectal cancer.
Secondary
- Determine the activity of this regimen, in terms of pathological complete response
rate, in these patients.
OUTLINE: This is a non-randomized, open-label, pilot study.
Patients receive cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, 36, 43, 50, 57, and
64 and fluorouracil IV continuously on days 1-42. Patients undergo whole-pelvic radiotherapy
once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Treatment continues in the
absence of disease progression or unacceptable toxicity.
Approximately 1-3 weeks after completion of study treatment, patients undergo surgical
resection followed by adjuvant chemotherapy off-study.
Patients are followed for up to 5 years.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed rectal adenocarcinoma meeting 1 of the following staging
criteria:
- Locally advanced disease
- Resectable (uT3) disease
- Primary gross transmural tumor that is not adherent to adjacent pelvic
structures by endorectal ultrasound
- Primary tethered or unresectable (cT4 or uT4) disease
- Primary tumor is contiguous with or adherent or fixed to adjacent
pelvic structures by clinical exam and CT scan
- Primary surgery would likely leave residual tumor
- Small volume extrapelvic metastases allowed
- Recurrent disease after definitive resection
- Disease limited to the pelvis
- Requires combined modality treatment
- Epidermal growth factor receptor status-positive, -negative, or -unknown
- If previously treated with adjuvant fluorouracil-based chemotherapy, no disease
recurrence during or within 12 months after completion of adjuvant therapy
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- ECOG 0 -1
Life expectancy
- Not specified
Hematopoietic
- Absolute neutrophil count ≥ 1,500/mm^3
- Hemoglobin > 8.0 g/dL
- Platelet count > 150,000/mm^3
Hepatic
- Not specified
Renal
- Creatinine ≤ 1.5 times upper limit of normal
Cardiovascular
- No myocardial infarction within the past 6 months
- No evidence of uncontrolled congestive heart failure requiring therapy
Other
- No other malignancy within the past 5 years except adequately treated basal cell or
squamous cell skin cancer or carcinoma in situ of the cervix
- No known severe hypersensitivity to cetuximab or any of its excipients
- No uncontrolled infection
- No high-grade bowel obstruction (bowel lumen ≤ 1 cm) unless patient has undergone
protective surgical diversion or endoscopic stenting procedure
- No other concurrent medical or psychiatric condition or disease that would preclude
study participation
- HIV negative
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for at least 3 months
after study treatment
PRIOR CONCURRENT THERAPY:
Biologic therapy
- No prior cetuximab
- No prior murine or chimeric monoclonal antibody therapy
- No prior biological response modifiers for metastatic colorectal cancer
- No concurrent anti-vascular endothelial growth factor/Flk-1 monoclonal antibody
therapy
- No other concurrent antibody therapy or immunotherapy
- No concurrent gene therapy
- No concurrent vaccine therapy
- No concurrent angiogenesis inhibitors, including thalidomide
Chemotherapy
- See Disease Characteristics
- No prior chemotherapy for metastatic colorectal cancer
- No other concurrent chemotherapy
Endocrine therapy
- No concurrent hormonal therapy
Radiotherapy
- No prior radiotherapy for metastatic colorectal cancer
- No prior pelvic radiotherapy
- No other concurrent radiotherapy
Surgery
- See Disease Characteristics
- Fully recovered from prior oncologic or other major surgery
Other
- No other prior therapy that targets the epidermal growth factor receptor pathway
- No other concurrent experimental therapy or drugs
- No concurrent matrix metalloprotease inhibitors
- No concurrent participation in another clinical study
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Safety profile
Outcome Time Frame:
2 years
Safety Issue:
Yes
Principal Investigator
Leonard B. Saltz, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Memorial Sloan-Kettering Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
04-006
NCT ID:
NCT00084773
Start Date:
March 2004
Completion Date:
March 2010
Related Keywords:
- Colorectal Cancer
- recurrent rectal cancer
- stage II rectal cancer
- stage III rectal cancer
- adenocarcinoma of the rectum
- Rectal Neoplasms
- Colorectal Neoplasms
Name | Location |
|---|---|
| Memorial Sloan-Kettering Cancer Center | New York, New York 10021 |
