Midostaurin (PKC412) for Locally Advanced Rectal Cancer
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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 |
- 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 ]
| Estimated Enrollment: | 30 |
| Study Start Date: | August 2011 |
| Estimated Primary Completion Date: | June 2013 (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 |
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| Contact: Theodore S Hong, MD | 617-724-1159 | tshong1@partners.org |
| 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 | Not yet recruiting |
| Boston, Massachusetts, United States, 02215 | |
| Contact: Harvey Mamon, MD, PhD 617-732-6310 hmamon@partners.org | |
| Principal Investigator: Harvey Mamon, MD, PhD | |
| 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: | August 17, 2012 |
| 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 September 26, 2012
