Ignite Creation Date:
2025-12-24 @ 10:13 PM
Ignite Modification Date:
2025-12-30 @ 3:00 PM
Study NCT ID:
NCT01198535
Status:
TERMINATED
Last Update Posted:
2015-05-18
First Post:
2010-09-09
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Phase I Study of Cetuximab With RO4929097 in Metastatic Colorectal Cancer
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
Phase I Study of Cetuximab With RO4929097 in Metastatic Colorectal Cancer
Status:
TERMINATED
Status Verified Date:
2012-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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.
Detailed Description:
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.
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.
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| NCI-2012-02905 | REGISTRY | CTRP (Clinical Trial Reporting Program) | View | |
| VICC GI 09106 | OTHER | Vanderbilt University/Ingram Cancer Center | View | |
| 8511 | OTHER | CTEP | View | |
| N01CM00100 | NIH | None | https://reporter.nih.gov/quic… | View |
| P30CA068485 | NIH | None | https://reporter.nih.gov/quic… | View |