Stage IVA Colon Cancer Clinical Trial
Official title:
Phase I Study of Cetuximab With RO4929097 in Metastatic Colorectal Cancer
The purpose of this study is to determine if a new drug, RO4929097, can work with cetuximab, a drug already approved for colorectal cancer, to help fight the patient's cancer. Cancers arise as a result of abnormal control of gene expression. One of the pathways that gets abnormally regulated in some cancers is the Notch pathway. RO4929097 is an investigational drug that blocks the activation of the Notch pathway. It is hoped that by blocking this abnormal activation, this drug may be helpful in patients with cancer but the investigators do not yet know if that is true. Cetuximab is an antibody against epidermal growth factor receptor and is known to have activity in metastatic colorectal cancer. Recent studies have shown that people with colorectal cancers that contain a mutation in a gene called K-ras do not benefit from receiving cetuximab. It is unknown if adding RO4929097 to cetuximab would benefit patients who have tumors with this mutation.
PRIMARY OBJECTIVES:
I. Determination of the maximum tolerated dose (MTD) of the combination of cetuximab and
RO4929097.
SECONDARY OBJECTIVES:
I. Safety and tolerability of the combination of cetuximab and RO4929097. II. Exploratory
analyses of anti-tumor effect with the combination. III. Laboratory correlatives exploring
response rate with notch receptors and ligand expression, correlation of response and
toxicity profiles to expression of EGFR pathway components, and evaluation of serum and
tissue markers of gamma-secretase inhibitor activity.
IV. Pharmacokinetic studies.
OUTLINE: This is a dose-escalation study of gamma-secretase/Notch signalling pathway
inhibitor RO4929097.
Phase I dose escalation: In this part of the study, the investigators are trying to find out
what is the highest tolerated dose of RO4929097 that can be safely combined with cetuximab.
The investigators will be testing two different cetuximab doses. One is the standard dose
(Arm A) and one is a little less than the standard dose (Arm B). Everyone will get treated
with cetuximab and R04929097 in this part of the study.
Phase I dose expansion: In this part of the study, the investigators will take the highest
tolerated dose found in the phase I part of the study and test a small number of people with
colorectal cancer to see if there is any activity with the combination of drugs. Everyone
will get treated with cetuximab and RO4929097 in this part of the study. This part of the
study will be restricted to patients whose tumors do not have a mutation in the K-ras gene.
RO4929097 is an investigational anti-cancer agent that has not yet been approved by the Food
and Drug Administration (FDA) for use in colorectal cancer. Cetuximab is FDA approved for
metastatic colorectal cancer.
After completion of study treatment, patients are followed up every 3 months.
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Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
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