Midostaurin (PKC412) for Locally Advanced Rectal Cancer

Phase 1

Completed

• Conditions: Adenocarcinoma of the Rectum
• Interventions: Drug: Midostaurin

• Registration Number: NCT01282502
• Lead Sponsor: 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.

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 Timeline

• Study First Submitted: 2011-01-21
• Study First Submitted QC: 2011-01-21
• Study First Posted: 2011-01-25
• Study Start: 2011-08
• Primary Completion: 2015-03
• Status Verified: 2018-12
• Study Completion: 2018-12
• Last Update Submitted: 2018-12-11
• Last Update Posted: 2018-12-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 19

Inclusion Criteria

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Midostaurin with chemoradiation	Midostaurin	-

Primary Outcome Measures

Name	Time	Method
To determine Maximum Tolerated Dose (MTD) of midostaurin in combination with standard 5-FU chemoradiation	1.5 years

Secondary Outcome Measures

Name	Time	Method
To determine surgical complication rate in patients who received preoperative radiation therapy	1.5 years
Perform an exploratory analysis of the impact of selected mutations in APC, PTEN, BRAF, NRAS, and PIK3CA, among other genes	1.5 year
To evaluate proteomic markers of response and resistance to midostaurin-based chemoradiation	1.5 years
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

Trial Locations

Locations (2)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Dana Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States