Midostaurin (PKC412) for Locally Advanced Rectal Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Massachusetts General Hospital
Sponsor:
Information provided by (Responsible Party):
Theodore Sunki Hong, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01282502
First received: January 21, 2011
Last updated: April 10, 2014
Last verified: April 2014

January 21, 2011
April 10, 2014
August 2011
June 2014   (final data collection date for primary outcome measure)
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 MTD of midostaurin in combination with standard 5-FU chemoradiation [ Time Frame: 1.5 years ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01282502 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
Midostaurin (PKC412) for Locally Advanced Rectal Cancer
Phase I Study of Chemoradiation With 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.

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.

Interventional
Phase 1
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Adenocarcinoma of the Rectum
Drug: Midostaurin
50 mg BID for 8 cycles
Experimental: Midostaurin with chemoradiation
Intervention: Drug: Midostaurin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
30
Not Provided
June 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Adenocarcinoma of the rectum
  • T3/4 or N+ disease
  • Life expectancy > 3 months
  • Normal organ and marrow function

Exclusion Criteria:

  • Metastatic disease
  • Pregnant or breastfeeding
  • Prior radiotherapy
  • Receiving other investigational agents
  • History of inflammatory bowel disease
  • Active scleroderma or CREST syndrome
  • Uncontrolled intercurrent illness
  • History of a different malignancy unless disease free for at least 5 years
  • HIV or active viral hepatitis
  • Impaired cardiac function
Both
18 Years and older
No
Contact: Theodore S Hong, MD 617-724-1159 tshong1@partners.org
United States
 
NCT01282502
10-457
Yes
Theodore Sunki Hong, Massachusetts General Hospital
Massachusetts General Hospital
Not Provided
Principal Investigator: Theodore S Hong, MD Massachusetts General Hospital
Massachusetts General Hospital
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP