Pre-operative 5-Fluorouracil (5-FU) and Sorafenib With External Radiation in Locally Advanced Rectal Cancer
The main purpose of this study is to find the maximum tolerable dose of sorafenib when administered along with another drug called 5-Fluorouracil (5-FU) and to find out more about whether these drugs, along with radiation, can help people with rectal cancer when given before surgery. 5-FU and radiation are both approved by the US Food and Drug Administration (FDA) for use in people with rectal cancer.
The investigators will utilize a standard 3 + 3 phase I study design. In the phase I part of the study, the investigators will attempt dose escalation of sorafenib in combination with standard infusional 5-FU and external beam at standard doses. Clinical staging should be done by endorectal ultrasound (ERUS) and/or pelvic magnetic resonance imaging (MRI) for T and N stage; chest and abdomen computed tomography (CT) for staging of metastatic disease; undergo sigmoidoscopy and/or colonoscopy done by crude odds ratios (CORS); biopsy is taken for diagnosis and extra is sent for tissue bank. At the maximum tolerated dose (MTD) of sorafenib we will expand the cohort to 6 more patients to further evaluate toxicity profile and efficacy.
Drug: 5-Fluorouracil (5-FU)
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Study of Pre-operative Continuous 5-FU, and Sorafenib With External Radiation Therapy in Locally Advanced Rectal Adenocarcinoma|
- Maximum Tolerated Dose (MTD) [ Time Frame: Start of treatment through end of follow up - average of 21 weeks ] [ Designated as safety issue: No ]To determine maximally tolerated dose of sorafenib when delivered concurrently with 5-FU and external beam radiation in patients with locally advanced rectal adenocarcinoma
- Number of Participants With Pathologic Response [ Time Frame: Start of treatment through end of follow up - average of 21 weeks ] [ Designated as safety issue: No ]To determine the pathologic response rate after pre-operative therapy and surgery
- Number of Participants With Serious Adverse Events (SAEs) [ Time Frame: Start of treatment through end of follow up - average of 21 weeks ] [ Designated as safety issue: Yes ]To further define safety profile of the combination. During the 5 1/2 weeks of radiation, participants will be seen in the study clinic and will have blood tests weekly.
|Study Start Date:||June 2011|
|Estimated Study Completion Date:||June 2015|
|Primary Completion Date:||November 2014 (Final data collection date for primary outcome measure)|
Experimental: Sorafenib Dose Escalation
Pre-operative Continuous 5-FU, and Sorafenib with External Radiation Therapy. Dose level -1 will only be evaluated if dose level 1 exceeds MTD. The sorafenib and infusional 5-FU will only be given Day 1-5(Monday-Friday) with radiation only.
In addition to radiation and 5-FU, sorafenib will be taken by mouth daily every day until the last day of radiation. The dose of sorafenib will be one of the following: 200 mg every other day, 200 mg daily, 400 mg daily, or 800 mg daily
Other Names:Drug: 5-Fluorouracil (5-FU)
5-FU will be delivered at a dose of 225 mg/m^2 daily through a catheter in a large vein continuously until the last day of radiation.
Other Names:Radiation: Radiation
Radiation sessions will be daily, Monday through Friday, except for holidays.
Participants' study regimen will include 5 ½ weeks of radiation. Radiation sessions will be daily, Monday through Friday, except for holidays. 5-FU will be delivered at a dose of 225 mg/m² daily through a catheter in a large vein continuously until the last day of radiation. In addition, sorafenib will be taken by mouth twice daily every day until the last day of radiation. The dose of sorafenib participants may receive will be one of the following: 200 mg every other day, 200 mg daily, 400 mg daily, or 800 mg daily. Following completion of this phase of the study, participants will receive no study drug or radiation for one month. At 4 to 5 weeks after stopping study drug and radiation, participants will have another CT scan or MRI to assess their cancer. About 6 to 8 weeks after the end of radiation, participants will undergo surgery and every effort will be made to remove the tumor. The surgery will occur just as it would if participants were not in the study, except that a portion of their tumor obtained during surgery will be used for research biomarker testing (as described in the consent form).
Approximately 6 -10 weeks after participants' surgery, when they have adequately healed, they may receive additional chemotherapy at their study doctor's discretion.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01376453
|United States, Florida|
|H. Lee Moffitt Cancer Center and Research Institute|
|Tampa, Florida, United States, 33612|
|Principal Investigator:||Richard Kim, M.D.||H. Lee Moffitt Cancer Center and Research Institute|