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
  Purpose

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 Intervention Phase
Adenocarcinoma of the Rectum
Drug: Midostaurin
Phase 1

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 30
Study Start Date: August 2011
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Midostaurin with chemoradiation Drug: Midostaurin
50 mg BID for 8 cycles

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01282502

Contacts
Contact: Theodore S Hong, MD 617-724-1159 tshong1@partners.org

Locations
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Theodore S Hong, MD    617-724-1159    tshong1@partners.org   
Principal Investigator: Theodore S Hong, MD         
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Harvey Mamon, MD, PhD    617-732-6310    hmamon@partners.org   
Principal Investigator: Harvey Mamon, MD, PhD         
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: Theodore S Hong, MD Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: Theodore Sunki Hong, Radiation Oncologist, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01282502     History of Changes
Other Study ID Numbers: 10-457
Study First Received: January 21, 2011
Last Updated: April 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Massachusetts General Hospital:
rectal cancer
chemotherapy
chemoradiation

Additional relevant MeSH terms:
Adenocarcinoma
Rectal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
4'-N-benzoylstaurosporine
Staurosporine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 27, 2014