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Phase I Study of Pre-operative Continuous 5-FU, and Sorafenib With External Radiation Therapy in Locally Advanced Rectal Adenocarcinoma

Phase 1
18 Years
Open (Enrolling)
Rectal Cancer

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Trial Information

Phase I Study of Pre-operative Continuous 5-FU, and Sorafenib With External Radiation Therapy in Locally Advanced Rectal Adenocarcinoma

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.

Inclusion Criteria:

- Histologically confirmed adenocarcinoma of the rectum that begins within 12 cm of the
anal verge as determined by sigmoidoscopy and/or colonoscopy with no evidence of
distant metastasis

- Locally advanced rectal cancer determined by any of the following features: Fixed or
immobile tumor on physical exam and/or; T3 disease with invasion through the
muscularis propria as defined by transrectal ultrasound, CT or MRI; T4 disease with
invasion of adjacent structures such as pelvic sidewall, sacrum, pelvis, bladder
and/or prostate as determined appropriate imaging modalities such as ultrasound, CT
or MRI; Any T with + N on CT scan/MRI or transrectal ultrasound

- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1

- Adequate bone marrow, liver and renal function as assessed by the following:
Hemoglobin > 9.0 g/dl, Absolute neutrophil count (ANC) > 1,500/mm^3, Platelet count >
100,000/mm^3, Total bilirubin < 1.5 times upper limit of normal (ULN), alanine
aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 times the ULN ( < 5
x ULN for patients with liver involvement), Creatinine < 1.5 times ULN

- Women of childbearing potential must have a negative serum pregnancy test performed
within 7 days prior to the start of treatment

- Women of childbearing potential and men must agree to use adequate contraception
(barrier method of birth control) prior to study entry and for the duration of study
participation. Men should use adequate birth control for at least three months after
the last administration of sorafenib.

- Ability to understand and the willingness to sign a written informed consent. A
signed informed consent must be obtained prior to any study specific procedures.

- Patients receiving anti-coagulation treatment with an agent such as warfarin or
heparin will be allowed to participate. For patients on warfarin, the INR should be
measured prior to initiation of sorafenib and monitored at least weekly, or as
defined by the local standard of care, until international normalized ratio (INR) is

Exclusion Criteria:

- Cardiac disease: Congestive heart failure > class II New York Heart Association
(NYHA). Patients must not have unstable angina (anginal symptoms at rest) or new
onset angina (began within the last 3 months) or myocardial infarction within the
past 6 months.

- Pelvic irradiation therapy.

- Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.

- Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic
pressure > 90 mmHg, despite optimal medical management.

- Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.

- Active clinically serious infection > Common Terminology Criteria for Adverse Events
(CTCAE) Grade 2.

- Thrombolic or embolic events such as a cerebrovascular accident including transient
ischemic, attacks, deep vein thrombosis (DVT) within the past 6 months.

- No active malignancy except for nonmelanoma skin cancer or in situ cervical cancer or
Treated non-pelvic cancer from which the patient has been continuously disease free
more than five years.

- Needing medical attention for serious bleeding in past 4 weeks.

- Previous chemotherapy except for antiangiogenic agent or tyrosine kinase inhibitor
(TKI) will be allowed as long as it is more than 5 years.

- Evidence or history of bleeding diathesis

- Use of St. John's Wort or rifampin

- Known or suspected allergy to sorafenib or any agent given in the course of this

- Any condition that impairs patient's ability to swallow whole pills.

- Any malabsorption problem.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum Tolerated Dose (MTD)

Outcome Description:

To determine maximally tolerated dose of sorafenib when delivered concurrently with 5-FU and external beam radiation in patients with locally advanced rectal adenocarcinoma

Outcome Time Frame:

Start of treatment through end of follow up - average of 21 weeks

Safety Issue:


Principal Investigator

Richard Kim, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

H. Lee Moffitt Cancer Center and Research Institute


United States: Institutional Review Board

Study ID:




Start Date:

June 2011

Completion Date:

July 2014

Related Keywords:

  • Rectal Cancer
  • External Radiation Therapy
  • Locally Advanced Rectal
  • Adenocarcinoma
  • Adenocarcinoma
  • Rectal Neoplasms



H. Lee Moffitt Cancer Center and Research InstituteTampa, Florida  33612