Bevacizumab, Erlotinib and 5-Fluorouracil With External Beam Radiation Therapy in Locally Advanced Rectal Cancer - Full Text View

Sponsors and Collaborators:	Massachusetts General Hospital Beth Israel Deaconess Medical Center Dana-Farber Cancer Institute Genentech
Information provided by:	Massachusetts General Hospital
ClinicalTrials.gov Identifier:	NCT00307736

Purpose

The purpose of this study is determine the safety of 5-fluorouracil, bevacizumab and erlotinib when administered in combination with external beam radiation therapy(Phase I portion) as well as to begin to collect information about whether this combination treatment is effective in treating(Phase II portion) patients with locally advanced rectal cancer.

Condition	Intervention	Phase
Rectal Cancer Adenocarcinoma of the Rectum	Drug: 5-fluorouracil Drug: bevacizumab Drug: erlotinib Procedure: External beam radiation therapy (EBRT)	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Dose Comparison, Single Group Assignment, Safety/Efficacy Study
Official Title:	A Phase I/II Study of Bevacizumab, Erlotinib and 5-Fluorouracil With Concurrent External Beam Radiation Therapy in Locally Advanced Rectal Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer Radiation Therapy

Drug Information available for: Fluorouracil Erlotinib hydrochloride Erlotinib Bevacizumab

U.S. FDA Resources

Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:

Determine the dose-limiting toxicity and the maximum tolerated dose of 5-FU, bevacizumab, and erlotinib when administered in combination with external beam radiation therapy [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
determine pathological response. [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Determine toxicity profile [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
determine survival, local control, progression free survival and duration of response [ Time Frame: TBD ] [ Designated as safety issue: No ]
determine the surgical morbidity after resection of rectal cancers following preoperative 5-FU, bevacizumab, erlotinib, and external beam radiation therapy. [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	32
Study Start Date:	May 2006
Estimated Primary Completion Date:	May 2009 (Final data collection date for primary outcome measure)

Intervention Details:

Given as a 24-hour infusion on days 1-14 of each 14-day cycle for a total of 3 cycles.

Given intravenously on day 1 of each 14-day cycle for a total of 3 cycles.

Taken orally on days 1-14 of each 14-day cycle for a total of 3 cycles.

Given on days 1-5 and 8-12

Detailed Description:

All participants will receive the following drugs: 5-fluorouracil (5-FU) given as a continuous 24-hour infusion; Bevacizumab given intravenously; erlotinib given orally at home. In the Phase I portion, we are looking for the highest dose of erlotinib that can be given safely in combination with the 5-FU, bevacizumab and radiation therapy. Therefore the dose of erlotinib may not be the same for each participant. The dose will increase until we find the highest dose without causing serious or unmanageable side effects.
Study treatment is given as an outpatient and consists of 14 day cycles with a total of 3 cycles. Patients will be given all three study drugs and radiation therapy on a monday (unless a monday falls on on a holiday).

This will be day 1 of the first treatment cycle. 5-FU is given continuously days 1-14. Bevacizumab is given on day 1. Erlotinib will be given on days 1-14. Radiation therapy will be performed on Days 1-5 and 8-12.

The following tests and procedures will be performed weekly while participants are receiving study treatment:

physical examination, measurement of vital signs, height and weight; performance status; blood work, urine sample.

At the end of treatment the following tests will be performed: physical examination and measurement of vital signs; performance status; blood work; CT scans of chest, abdomen and pelvis. Patients will also be evaluated for surgery at this time. Patients will be followed every three months for the first three years after surgery, then every 6 months for the next two years.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Histologically confirmed primary adenocarcinoma of the rectum that begins within 15cm of the anal verge as determined by sigmoidoscopy or colonoscopy
Clinical T3 or T4 tumors as determined by endoscopic ultrasound and/or rectal MRI
ECOG performance status of 0-2
18 years of age or older
Creatinine of < 2.0
Adequate hepatic function
Adequate hematopoietic function
Use of effective means of contraception in subjects of child-bearing potential

Exclusion Criteria:

Evidence of metastatic disease as determined by chest/abdominal/pelvic CT or physical exam
Prior chemotherapy or radiation therapy for treatment of colorectal cancer
Prior treatment with 5-FU
Prior treatment with a tyrosine kinase inhibitor, EGFR inhibitor, or VEGF inhibitor
Patients must not be receiving any other investigational agent
Prior malignancy within the last 5 years except for completely excised skin cancer, in situ cervical cancer
Warfarin anticoagulation
Co-existent malignant disease
Current or recent participation in a clinical trial (within 4 weeks from the first day of treatment)
Pregnancy
Blood pressure of >150/100 mmHg
Unstable angina
NYHA Grade II or greater congestive heart failure
History of myocardial infarction within 6 months
History of stroke within 6 months
Clinically significant peripheral vascular disease
Evidence of bleeding diathesis or coagulopathy
Presence of central nervous system or brain metastases
Major surgical procedure, open biopsy, or significant trauma injury within 28 days prior to day 0, anticipation of need for major surgical procedure during the course of the study
Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to day 0
Pregnant or lactating
Urine protein:creatinine ratio > or equal to one at screening
History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to day 0]
Serious, non-healing wound, ulcer, or bone fracture

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00307736

Contacts

Contact: Lawrence S. Blaszkowsky, MD

617-724-4637

Locations

United States, Massachusetts
Massachusetts General Hospital	Recruiting
Boston, Massachusetts, United States, 02115
Dana-Farber Cancer Institute	Recruiting
Boston, Massachusetts, United States, 02115
Beth Israel Deaconess Medical Center	Recruiting
Boston, Massachusetts, United States, 02115

Sponsors and Collaborators

Massachusetts General Hospital

Beth Israel Deaconess Medical Center

Dana-Farber Cancer Institute

Genentech

Investigators

Principal Investigator:

Lawrence S. Blaszkowsky, MD

Massachusetts General Hospital

More Information

No publications provided

Responsible Party:	Massachusetts General Hospital ( Lawrence Blaszkowsky, MD )
Study ID Numbers:	05-345
Study First Received:	March 24, 2006
Last Updated:	February 26, 2009
ClinicalTrials.gov Identifier:	NCT00307736 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Massachusetts General Hospital:

Fluorouracil
bevacizumab
erlotinib
external beam radiation therapy
EBRT

Study placed in the following topic categories:

Antimetabolites
Erlotinib
Digestive System Neoplasms
Immunologic Factors
Rectal Neoplasms
Gastrointestinal Diseases
Rectal Neoplasm
Bevacizumab
Intestinal Diseases
Protein Kinase Inhibitors
Angiogenesis Inhibitors

Immunosuppressive Agents
Rectal Diseases
Intestinal Neoplasms
Carcinoma
Digestive System Diseases
Rectal Cancer
Fluorouracil
Gastrointestinal Neoplasms
Adenocarcinoma
Colorectal Neoplasms
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Gastrointestinal Diseases
Rectal Neoplasms
Antineoplastic Agents
Physiological Effects of Drugs
Bevacizumab
Protein Kinase Inhibitors
Rectal Diseases
Neoplasms by Site
Therapeutic Uses
Growth Inhibitors
Angiogenesis Modulating Agents

Erlotinib
Digestive System Neoplasms
Neoplasms by Histologic Type
Growth Substances
Enzyme Inhibitors
Intestinal Diseases
Angiogenesis Inhibitors
Immunosuppressive Agents
Intestinal Neoplasms
Pharmacologic Actions
Carcinoma
Neoplasms
Digestive System Diseases
Fluorouracil
Gastrointestinal Neoplasms

ClinicalTrials.gov processed this record on September 11, 2009