RO4929097 in Treating Patients With Metastatic Colorectal Cancer
|Recurrent Colon Cancer Recurrent Rectal Cancer Stage IV Colon Cancer Stage IV Rectal Cancer||Drug: gamma-secretase/Notch signalling pathway inhibitor RO4929097 Other: laboratory biomarker analysis||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 2 Open-Label Study of RO4929097 in Metastatic Colorectal Cancer|
- Number of Participants With Objective Radiographic Response (ORR) [ Time Frame: 2 months from enrollment for each participant ]To determine the objective radiographic response rate associated with RO4929097 in patients with metastatic colorectal cancer who have progressed following at least 2 prior treatments in the metastatic setting. Radiologic assessment of tumor burden (CT scans of the chest, abdomen and pelvis, or MRI of the abdomen and pelvis and CT of the chest) was scheduled every 8 weeks. Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) were used for evaluation of the primary endpoint.
- Participant Overall Survival (OS) Rate [ Time Frame: Study duration of 12 months ]Overall Survival defined as the time from start of treatment until death as a result of any cause, with patients censored at the date of last follow-up if still alive. The Kaplan-Meier method was used to estimate all time-to-event functions. Statistical analysis was performed using Stata SE 9.0 software and SAS 9.2 software.
- Participant Progression Free Survival (PFS) Rate [ Time Frame: Study duration of 12 months ]Progression-Free Survival defined as the time from start of treatment until disease progression or death as a result of any cause. Patients were re-evaluated for response every 8 weeks. Response and progression were evaluated using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) [Eur J Ca 45:228-247, 2009]. Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria.
- Number of Related Serious Adverse Events (SAEs) [ Time Frame: Study duration of 12 months ]Study drug related grade 3-4 toxicities. To measure Adverse Events, investigators used the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
|Study Start Date:||May 2010|
|Study Completion Date:||March 2012|
|Primary Completion Date:||May 2011 (Final data collection date for primary outcome measure)|
Experimental: Treatment (RO4929097)
See detailed description.
Drug: gamma-secretase/Notch signalling pathway inhibitor RO4929097
Other Names:Other: laboratory biomarker analysis
I. To determine the objective radiographic response rate associated with RO4929097 in patients with metastatic colorectal cancer who have progressed following at least two prior treatments in the metastatic setting.
I. To determine the progression-free survival (PFS) and overall survival (OS) associated with this agent.
II. To determine the safety and tolerability of RO4929097 in this patient population.
III. To assess whether response correlates with up regulation of the Notch pathway, to be determined through immunohistochemical analysis of Notch1, ICN and HES1 on available paraffin-embedded tissue samples (exploratory aim).
Participants will take 20 mg of RO4929097 by mouth at home in the morning for 3 days and then not take it for 4 days, continuously. The tablet is to be taken at approximately the same time the days they take it on an empty stomach, 1 hour before a meal or 2 hours after a meal. Participants will be asked to keep a "pill diary" recording each dose of study drug (including missed, skipped, or vomited doses) and return the diary to the study staff each visit. Participants will be informed that tablets should not be broken or opened; that they should avoid eating grapefruits or drinking grapefruit juice while on the study; that if they miss a dose of study drug, they should not try to make up that dose; that instead, they should wait until their next scheduled dose. Participants will see their study doctor and undergo standard blood work (approximately 12 mL) every 4 weeks. During these visits, participants will be asked about side effects of the RO4929097 and undergo a physical examination. Participants will continue taking the RO4929097 as long as they are tolerating it and as long as the cancer is shrinking or remains stable.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01116687
|United States, Florida|
|H. Lee Moffitt Cancer Center and Research Institute|
|Tampa, Florida, United States, 33612|
|Principal Investigator:||Jonathan Strosberg||H. Lee Moffitt Cancer Center and Research Institute|