A Phase II Study of BAY 43-9006 (Sorafenib) in Combination With Cetuximab (Erbitux®) in EGFR Expressing Metastatic Colorectal Cancer (CRC)
Protocol # 06-C-0164, NCT00326495
- Why is this trial important?
- Who is eligible for this trial?
- What types of drugs or therapies are being used?
- What is the study outline?
- What is the frequency and duration of the visits?
- What are the costs?
- Who is the Principal Investigator?
- Where is this trial taking place?
- Who are the contacts for this trial?
- Where can additional information be found?
Why is this trial important?
Many types of cancer, especially colorectal cancer, show increased activity or increased amounts of a protein called epidermal growth factor receptor (EGFR). EGFR stimulates cell growth and multiplication in response to other proteins called epidermal growth factors. Cetuximab (Erbitux®) is a monoclonal antibody that binds to and blocks EGFR activity.
Cetuximab is FDA approved for treating EGFR-expressing metastatic colorectal cancer; however, it produces significant tumor shrinkage in only about 10% of patients when used as a single agent and recent results from clinical trials indicate that patients who have tumors with a mutation/defect in a gene called KRAS do not benefit from treatment with cetuximab alone. In this research study, an additional drug, sorafenib, that may block the effect of the KRAS mutation along with blocking VEGFR2 and hence angiogenesis, is being administered along with cetuximab to determine if the combined drugs will have improved outcomes for patients with and without the KRAS mutation.
Who is eligible for this trial? (PDQ)
- Histologically or cytologically confirmed metastatic colorectal cancer
- Evidence of disease recurrence or progression after one or more prior chemotherapy regimens for the treatment of metastatic disease
- Measurable disease
- KRAS wild type and/or mutant tumors allowed
- At least one lesion amenable to biopsy (biopsies are optional)
- Expression in tumor cells of epidermal growth factor receptor (EGFR)
- Must have received or have declined one or more prior fluorouracil-containing combination chemotherapy regimens for metastatic disease
- No known brain metastasis
- Not eligible for or refused tumor resection
- No prior sorafenib or cetuximab
- Not pregnant or nursing
- Fertile patients must use effective contraception before, during, and for at least 2 months after completion of study treatment
- Able to swallow tablets
What types of drugs or therapies are being used?
Cetuximab is combined with another targeted drug called sorafenib (Nexavar®) to treat patients with metastatic colorectal cancer whose tumors show EGFR activity. Sorafenib blocks the activity of two other proteins called vascular endothelial growth factor receptor (VEGFR) and Raf kinase. VEGFR stimulates the growth of blood vessels to tumors (a process called angiogenesis), and Raf kinase is a key molecule in relaying signals from growth factor receptors and KRAS to the interior of the cell, where the signals are converted into changes in gene activity that lead to cell growth and multiplication. Cetuximab is given intravenously once a week; sorafenib is administered by mouth twice a day.
What is the study outline? (PDQ)
- Patients receive oral sorafenib twice daily on days 1-28 and cetuximab IV over 1-2 hours once a week on days 1, 8, 15 and 22; treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity
- Blood samples are collected periodically and examined for biomarkers by enzyme immunoassay
- Tumor biopsy is obtained prior to treatment and after 4 weeks of treatment (optional)
- DCE-MRI scans are performed prior to treatment and after 8 weeks of treatment to evaluate tumor vascularity and metabolism
- After completion of study treatment, patients are followed for 4 weeks
What is the frequency and duration of the visits?
Patients are admitted to the hospital for the first 2-3 days for the initiation of treatment. From then on the treatment is all out-patient, once a week clinic visits. From cycle 2 onwards, there is an option to receive some doses of cetuximab by local oncologist, reducing the number of visits to NCI's Clinical Center, but this needs to be arranged on a case-by-case basis.
What are the costs?
There is no charge for medical care received at the National Institutes of Health (NIH) Clinical Center. Patients will be responsible for travel costs for their initial screening visits. In most cases, once patients are enrolled in a trial, the National Cancer Institute (NCI) will pay the transportation costs for all subsequent trial-related visits for patients who do not live in the local area. In addition, these patients will receive a small per diem to help offset the costs of meals and lodging if they are being treated as outpatients.
It will be important to maintain your current insurance plan to cover all medical care that is provided away from the NIH Clinical Center.
No U.S. citizen or permanent U.S. resident residing in the U.S. who otherwise meets the eligibility requirements will be denied enrollment in clinical research protocols because of their inability to pay the costs of travel and subsistence.
Who is the Principal Investigator?
Dr. Kummar received her medical degree from Lady Hardinge Medical College, New Delhi, India, and her internal medicine residency training from Emory University, Atlanta, GA. Upon completion of her fellowship training in medical oncology and hematology from the National Institutes of Health, Bethesda, Maryland, she joined Yale Cancer Center, Yale University, New Haven, CT, as an assistant professor in medical oncology. In 2004, Dr. Kummar moved back to NCI and is currently head of the Early Clinical Trials Development in the Office of the Director, Division of Cancer Treatment and Diagnosis, National Cancer Institute. Her research interests focus on the early development (Phase I/II trials) of novel therapies for cancer.
Where is this trial taking place?
NIH Clinical Center
National Institutes of Health
NCI Medical Oncology Branch and Affiliates, Developmental Therapeutics Section
10 Center Drive
Bethesda, Maryland 20892
Who are the contacts for this trial?
Shivaani Kummar, M.D., F.A.C.P.
Principal Investigator
Phone: 301-435-0517
Fax: 301-496-0826
kummars@mail.nih.gov
Referrals:
Janelle Bingham, R.N.
Referral Coordinator
Phone: 301-435-2715
Fax: 301-451-5433
jbingham@mail.nih.gov
Lauren Powell
Referral Coordinator
Phone: 301-451-0992
Fax: 301-480-6044
powelllr@mail.nih.gov
Deborah Allen, R.N., O.C.N.
Research Nurse
Phone: 301-402-5640
Fax: 301-480-7281
allendeb@mail.nih.gov
Where can additional information be found?
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