Clinical trial NCT01282502: Midostaurin (PKC412) for Locally Advanced Rectal Cancer
Official title: Phase I Study of Chemoradiation With Midostaurin (PKC412) For Locally Advanced Rectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Adenocarcinoma of the Rectum
Keywords: rectal cancer
chemotherapy
chemoradiation
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2011-01-25
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: To determine Maximum Tolerated Dose (MTD) of midostaurin in combination with standard 5-FU chemoradiation
timeFrame: 1.5 years
Secondary outcomes:
measure: 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)
timeFrame: 1.5 years
measure: To determine surgical complication rate in patients who received preoperative radiation therapy
timeFrame: 1.5 years
measure: Perform an exploratory analysis of the impact of selected mutations in APC, PTEN, BRAF, NRAS, and PIK3CA, among other genes
timeFrame: 1.5 year
measure: To evaluate proteomic markers of response and resistance to midostaurin-based chemoradiation
timeFrame: 1.5 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Theodore S Hong, MD
role: PRINCIPAL_INVESTIGATOR
References: