Midostaurin (PKC412) for Locally Advanced Rectal Cancer
This study combines midostaurin (PKC412) with radiation and a standard chemotherapy drug call 5-Fluorouracil (5-FU) for subjects with advanced rectal cancer. Midostaurin is a type of kinase inhibitor which works by blocking proteins associated with cancer cell growth. Previous studies also suggest that midostaurin may help increase the effectiveness of radiation therapy. In this research we are looking for the highest dose of midostaurin that can be given safely in combination with standard chemoradiation.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Study of Chemoradiation With Midostaurin (PKC412) For Locally Advanced Rectal Cancer|
- To determine Maximum Tolerated Dose (MTD) of midostaurin in combination with standard 5-FU chemoradiation [ Time Frame: 1.5 years ] [ Designated as safety issue: Yes ]
- To determine the rate of Dworak Tumor Regression Grade 3/4 for locally advanced rectal cancer treated with study combination at the MTD, stratified by KRAS status (mutant vs. wild type) [ Time Frame: 1.5 years ] [ Designated as safety issue: No ]
- To determine surgical complication rate in patients who received preoperative radiation therapy [ Time Frame: 1.5 years ] [ Designated as safety issue: Yes ]
- Perform an exploratory analysis of the impact of selected mutations in APC, PTEN, BRAF, NRAS, and PIK3CA, among other genes [ Time Frame: 1.5 year ] [ Designated as safety issue: No ]
- To evaluate proteomic markers of response and resistance to midostaurin-based chemoradiation [ Time Frame: 1.5 years ] [ Designated as safety issue: No ]
|Study Start Date:||August 2011|
|Estimated Primary Completion Date:||June 2014 (Final data collection date for primary outcome measure)|
|Experimental: Midostaurin with chemoradiation||
50 mg BID for 8 cycles
Midostaurin capsules will be taken by mouth for 8 weeks. For the first 2 weeks midostaurin will be taken alone (no chemoradiation). After 2 weeks standard chemoradiation will be added to the midostaurin regimen. Subjects receive midostaurin and chemoradiation for an additional 6 weeks. Physical exams will be done weekly. Blood samples will be taken and an optional tumor biopsy will be performed in week 2.
4-5 weeks after completing chemoradiation and midostaurin subjects will undergo surgery as standard of care. Tumor tissue from the surgery will be used for research purposes. A Ct scan of chest, abdomen, and pelvis will be performed.
After completion of surgery, subjects will have an end of study visit with physical exam, blood tests. CT scans of chest, abdomen, and pelvis will be performed yearly for 5 years.
|Contact: Theodore S Hong, MDfirstname.lastname@example.org|
|United States, Massachusetts|
|Massachusetts General Hospital||Recruiting|
|Boston, Massachusetts, United States, 02114|
|Contact: Theodore S Hong, MD 617-724-1159 email@example.com|
|Principal Investigator: Theodore S Hong, MD|
|Dana Farber Cancer Institute||Recruiting|
|Boston, Massachusetts, United States, 02215|
|Contact: Harvey Mamon, MD, PhD 617-732-6310 firstname.lastname@example.org|
|Principal Investigator: Harvey Mamon, MD, PhD|
|Principal Investigator:||Theodore S Hong, MD||Massachusetts General Hospital|