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Midostaurin (PKC412) for Locally Advanced Rectal Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01282502
Recruitment Status : Completed
First Posted : January 25, 2011
Last Update Posted : December 12, 2018
Information provided by (Responsible Party):
Theodore Sunki Hong, Massachusetts General Hospital

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
Adenocarcinoma of the Rectum Drug: Midostaurin 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
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 : August 2011
Actual Primary Completion Date : March 2015
Actual Study Completion Date : December 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Midostaurin

Arm Intervention/treatment
Experimental: Midostaurin with chemoradiation Drug: Midostaurin
50 mg BID for 8 cycles

Primary Outcome Measures :
  1. To determine Maximum Tolerated Dose (MTD) of midostaurin in combination with standard 5-FU chemoradiation [ Time Frame: 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) [ Time Frame: 1.5 years ]
  2. To determine surgical complication rate in patients who received preoperative radiation therapy [ Time Frame: 1.5 years ]
  3. 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 ]
  4. To evaluate proteomic markers of response and resistance to midostaurin-based chemoradiation [ Time Frame: 1.5 years ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01282502

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United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Massachusetts General Hospital
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Principal Investigator: Theodore S Hong, MD Massachusetts General Hospital

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Responsible Party: Theodore Sunki Hong, Radiation Oncologist, Massachusetts General Hospital Identifier: NCT01282502    
Other Study ID Numbers: 10-457
First Posted: January 25, 2011    Key Record Dates
Last Update Posted: December 12, 2018
Last Verified: December 2018
Keywords provided by Theodore Sunki Hong, Massachusetts General Hospital:
rectal cancer
Additional relevant MeSH terms:
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Rectal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action