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

This study has been completed.
Sponsor:
Collaborators:
Beth Israel Deaconess Medical Center
Dana-Farber Cancer Institute
Genentech, Inc.
Information provided by (Responsible Party):
Lawrence S. Blaszkowsky, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00307736
First received: March 24, 2006
Last updated: April 25, 2012
Last verified: April 2012

March 24, 2006
April 25, 2012
May 2006
April 2010   (final data collection date for primary outcome measure)
  • 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 ]
  • 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
  • determine pathological response.
Complete list of historical versions of study NCT00307736 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Determine toxicity profile
  • determine survival, local control, progression free survival and duration of response
  • determine the surgical morbidity after resection of rectal cancers following preoperative 5-FU, bevacizumab, erlotinib, and external beam radiation therapy.
Not Provided
Not Provided
 
Bevacizumab, Erlotinib and 5-Fluorouracil With External Beam Radiation Therapy in Locally Advanced Rectal Cancer
A Phase I/II Study of Bevacizumab, Erlotinib and 5-fluorouracil With Concurrent External Beam Radiation Therapy in Locally Advanced Rectal Cancer

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.

  • 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.
Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Rectal Cancer
  • Adenocarcinoma of the Rectum
  • Drug: 5-fluorouracil
    Given as a 24-hour infusion on days 1-14 of each 14-day cycle for a total of 3 cycles.
  • Drug: bevacizumab
    Given intravenously on day 1 of each 14-day cycle for a total of 3 cycles.
  • Drug: 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
Not Provided
Blaszkowsky LS, Ryan DP, Szymonifka J, Borger DR, Zhu AX, Clark JW, Kwak EL, Mamon HJ, Allen JN, Vasudev E, Shellito PC, Cusack JC, Berger DL, Hong TS. Phase I/II study of neoadjuvant bevacizumab, erlotinib and 5-fluorouracil with concurrent external beam radiation therapy in locally advanced rectal cancer. Ann Oncol. 2014 Jan;25(1):121-6. doi: 10.1093/annonc/mdt516.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
32
July 2011
April 2010   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00307736
05-345
Yes
Lawrence S. Blaszkowsky, MD, Massachusetts General Hospital
Massachusetts General Hospital
  • Beth Israel Deaconess Medical Center
  • Dana-Farber Cancer Institute
  • Genentech, Inc.
Principal Investigator: Lawrence S. Blaszkowsky, MD Massachusetts General Hospital
Massachusetts General Hospital
April 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP