Midostaurin (PKC412) for Locally Advanced Rectal Cancer

Adenocarcinoma of the Rectum Clinical Trial

Official title:

Phase I Study of Chemoradiation With Midostaurin (PKC412) For Locally Advanced Rectal Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01282502
• Other study ID #: 10-457
• Status: Completed
• Phase: Phase 1
• Start date: August 2011
• Est. completion date: December 2018

Study information

• Verified date: December 2018
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: December 2018
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Rectum
• Rectal Neoplasms

Intervention

Drug:
• Midostaurin
50 mg BID for 8 cycles

Locations

Country	Name	City	State
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Massachusetts General Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine Maximum Tolerated Dose (MTD) of midostaurin in combination with standard 5-FU chemoradiation		1.5 years
Secondary	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
Secondary	To determine surgical complication rate in patients who received preoperative radiation therapy		1.5 years
Secondary	Perform an exploratory analysis of the impact of selected mutations in APC, PTEN, BRAF, NRAS, and PIK3CA, among other genes		1.5 year
Secondary	To evaluate proteomic markers of response and resistance to midostaurin-based chemoradiation		1.5 years