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Midostaurin (PKC412) for Locally Advanced Rectal Cancer

Sponsor
Massachusetts General Hospital (Other)
Overall Status
Completed
CT.gov ID
NCT01282502
Collaborator
(none)
19
Enrollment
2
Locations
1
Arm
88
Duration (Months)
9.5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

Detailed Description

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
19 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase I Study of Chemoradiation With Midostaurin (PKC412) For Locally Advanced Rectal Cancer
Study Start Date :
Aug 1, 2011
Actual Primary Completion Date :
Mar 1, 2015
Actual Study Completion Date :
Dec 1, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: Midostaurin with chemoradiation

Drug: Midostaurin
50 mg BID for 8 cycles

Outcome Measures

Primary Outcome Measures

  1. To determine Maximum Tolerated Dose (MTD) of midostaurin in combination with standard 5-FU chemoradiation [1.5 years]

Secondary Outcome Measures

  1. 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) [1.5 years]

  2. To determine surgical complication rate in patients who received preoperative radiation therapy [1.5 years]

  3. Perform an exploratory analysis of the impact of selected mutations in APC, PTEN, BRAF, NRAS, and PIK3CA, among other genes [1.5 year]

  4. To evaluate proteomic markers of response and resistance to midostaurin-based chemoradiation [1.5 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Massachusetts General Hospital Boston Massachusetts United States 02114
2 Dana Farber Cancer Institute Boston Massachusetts United States 02215

Sponsors and Collaborators

  • Massachusetts General Hospital

Investigators

  • Principal Investigator: Theodore S Hong, MD, Massachusetts General Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Theodore Sunki Hong, Radiation Oncologist, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01282502
Other Study ID Numbers:
  • 10-457
First Posted:
Jan 25, 2011
Last Update Posted:
Dec 12, 2018
Last Verified:
Dec 1, 2018
Keywords provided by Theodore Sunki Hong, Radiation Oncologist, Massachusetts General Hospital
rectal cancer
chemotherapy
chemoradiation
Additional relevant MeSH terms:
Rectal Neoplasms
Midostaurin

Study Results

No Results Posted as of Dec 12, 2018