View Clinical Trial (Medical Research Study)
A Preoperative Biological Trial of Cetuximab, Dasatinib or the Combination in Colorectal Cancer Patients With Resectable Liver Metastases
| City: |
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Nashville |
| State: |
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Tennessee |
| Zip Code: |
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37232 |
| Conditions: |
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Colorectal Cancer - Metastatic Cancer |
| Purpose: |
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RATIONALE: Monoclonal antibodies, such as cetuximab, 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. Dasatinib may stop the growth of
tumor cells by blocking some of the enzymes needed for cell growth. Giving cetuximab and/or
dasatinib before surgery may make the tumor smaller and reduce the amount of normal tissue
that needs to be removed.
PURPOSE: This early phase I trial is studying how well cetuximab and/or dasatinib works in
treating patients with colorectal cancer and liver metastases that can be removed by
surgery.
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| Study Summary: |
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OBJECTIVES:
- To evaluate the biological effects of cetuximab and/or dasatinib on EGFR- and
Src-signaling pathways in patients with colorectal cancer and resectable liver
metastases.
OUTLINE: This is a multicenter study. Patients are initially enrolled in cohort A. Once
cohort A is completed, additional patients are enrolled and randomized to treatment in
either cohorts B or C. If a significant biological effect is seen in cohorts B or C,
additional patients are enrolled in cohort D.
- Cohort A: Patients receive no systemic neoadjuvant therapy between the time of
diagnostic biopsy and definitive surgical resection of liver metastases.
- Cohort B: Patients receive cetuximab IV over 60-120 minutes on days 1 and 8.
- Cohort C: Patients receive oral dasatinib once daily on days 1-14.
- Cohort D: Patients receive cetuximab IV over 60-120 minutes on days 1 and 8 and oral
dasatinib once daily on days 1-14.
All patients undergo definitive surgical resection of liver metastases on day 15.
Patients undergo tumor tissue (from initial liver tumor biopsies and liver resection
samples), serum, and peripheral blood mononuclear cell sample collection periodically for
biomarker analysis via IHC.
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| Criteria: |
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- Patients must have histologically confirmed adenocarcinoma arising from the large
intestine that has metastasized to the liver. Liver metastases may be synchronous or
metachronous.
- The liver metastases must be considered surgically resectable prior to the initiation
of study drugs.
- Prior chemotherapy or chemoradiotherapy for colorectal cancer is allowed provided
that toxicities from prior therapy have resolved to Grade 1 or less. No prior
anti-EGFR or anti-Src therapy is allowed.
- Age >18 years.
- ECOG performance status < 1 (Karnofsky >60%)
- Patients must have organ and marrow function within the parameter defined below:
- absolute neutrophil count >1.5 x 109/L
- hemoglobin ≥ 9.0 Gm/dL
- platelets >100 x 109/L
- total bilirubin ≤ 1.5 x IULN
- AST(SGOT)/ALT(SGPT)< 5 x institutional upper limit of normal
- creatinine <1.5 institutional ULN
- Women must have a negative pregnancy test. Women of child-bearing potential and men
must agree to use adequate contraception (hormonal or barrier method of birth
control; abstinence) prior to study entry and for the duration of study
participation. Should a woman become pregnant or suspect she is pregnant while
participating in this study, she should inform her treating physician immediately.
- Ability to understand and the willingness to sign a written informed consent
document.
- Although K-Ras status will be evaluated in the tumor, wild type K-Ras status is not
an eligibility criterion.
Exclusion Criteria
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have not
recovered from adverse events due to agents administered more than 4 weeks earlier.
- Patients receiving any other investigational agents.
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to cetuximab or dasatinib.
- Uncontrolled intercurrent illness including, but not limited to ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.
- Pregnant women are excluded from this study because of the potential for teratogenic
or abortifacient effects. Because there is an unknown but potential risk for adverse
events in nursing infants secondary to treatment of the mother with cetuximab or
dasatinib, breastfeeding should be discontinued if the mother is treated with
cetuximab or dasatinib.
- Patients with immune deficiency are at increased risk of lethal infections when
treated with marrow-suppressive therapy. Therefore, HIV-positive patients receiving
combination anti-retroviral therapy are excluded from the study because of possible
pharmacokinetic interactions with cetuximab or dasatinib. Appropriate studies will
be undertaken in patients receiving combination anti-retroviral therapy when
indicated.
- Patients on potent CYP3A4 inducers and inhibitors.
Inclusion of Women and Minorities Both men and women and members of all races and ethnic
groups are eligible for this trial.
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| NCT ID: |
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NCT00835679 |
| Primary Contact: |
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Principal Investigator
Emily Chan, MD, Ph.D.
Vanderbilt-Ingram Cancer Center
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| Backup Contact: |
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N/A |
| Location Contact: |
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Nashville, Tennessee 37232
United States
Clinical Trials Office - Vanderbilt-Ingram Cancer Center
Phone: 800-811-8480
Site Status: Recruiting |
| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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May 19, 2013 |
| Modifications to this listing: |
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