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

Rectal Cancer Clinical Trial

Official title:

A Phase I/II Study of Bevacizumab, Erlotinib and 5-fluorouracil With Concurrent External Beam Radiation Therapy in Locally Advanced Rectal Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00307736
• Other study ID #: 05-345
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: March 24, 2006
• Last updated: April 25, 2012
• Start date: May 2006
• Est. completion date: July 2011

Study information

• Verified date: April 2012
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: July 2011
• Est. primary completion date: April 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Rectum
• Rectal Cancer
• Rectal Neoplasms

Intervention

Drug:
• 5-fluorouracil
Given as a 24-hour infusion on days 1-14 of each 14-day cycle for a total of 3 cycles.
• bevacizumab
Given intravenously on day 1 of each 14-day cycle for a total of 3 cycles.
• erlotinib
Taken orally on days 1-14 of each 14-day cycle for a total of 3 cycles.

Procedure:
• External beam radiation therapy (EBRT)
Given on days 1-5 and 8-12

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (4)

Lead Sponsor	Collaborator
Massachusetts General Hospital	Beth Israel Deaconess Medical Center, Dana-Farber Cancer Institute, Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		3 years	Yes
Primary	determine pathological response.		3 years	No
Secondary	Determine toxicity profile		3 years	Yes
Secondary	determine survival, local control, progression free survival and duration of response		TBD	No
Secondary	determine the surgical morbidity after resection of rectal cancers following preoperative 5-FU, bevacizumab, erlotinib, and external beam radiation therapy.		3 years	No