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

NCT00307736 | Completed Phase 1 Results DMC

• 1 other identifier: 05-345
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Rectal Cancer; Adenocarcinoma of the Rectum

Keywords

Fluorouracil; bevacizumab; erlotinib; external beam radiation therapy; EBRT

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of Erlotinib When Administered in Combination With 5-fluorouracil (5-FU), Bevacizumab, and External Beam Radiation Therapy

  MTD of Erlotinib was determined using a traditional 3 + 3 dose escalation scheme of three dose levels (50,100,150mg). Successive cohorts of 3-6 patients were enrolled into dose escalation cohorts for 14 day cycles. MTD reflects the highest dose of Erlotinib that had ≤1 out of 6 patients with Dose-Limiting Toxicity (DLT) at the highest dose level below the maximally administered dose. The maximally administered dose is the first dose that causes DLT in \>33% of patients. DLT was defined as: Any grade 4 neutropenia, Any grade 3 thrombocytopenia, or Any ≥ grade 3 non-hematologic toxicity that results in greater than 7 days interruption in therapy.

  3 years

Secondary Outcomes (3)

• Summary of Grade 3 or Greater Toxicity

  3 years

• Percentage of Participants With Disease-free Survival

  1, 2, 3 years

• Post-operative Complications After Resection of Rectal Cancers Following Preoperative 5-FU, Bevacizumab, Erlotinib, and External Beam Radiation Therapy.

  3 years

Other Outcomes (1)

• Pathologic Complete Response

  3 years

Study Arms (1)

Chemotherapy and radiation

EXPERIMENTAL

Continuous infusion 5-fluorouracil 225 mg/M2/d, bevacizumab 5 mg/kg IV q 14 days, erlotinib 50-150 mg orally daily for duration of radiation.

Drug: 5-fluorouracil; Drug: bevacizumab; Drug: erlotinib; Procedure: External beam radiation therapy (EBRT)

Interventions

5-fluorouracil DRUG

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

Chemotherapy and radiation

bevacizumab DRUG

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

Chemotherapy and radiation

erlotinib DRUG

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

Chemotherapy and radiation

External beam radiation therapy (EBRT) PROCEDURE

Given on days 1-5 and 8-12

Chemotherapy and radiation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Beth Israel Deaconess Medical Center: collaborator
• Dana-Farber Cancer Institute: collaborator
• Genentech, Inc.: collaborator

Study Sites (3)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02115, United States

Location

Related Publications (1)

• 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.

  PMID: 24356623 DERIVED

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Fluorouracil; Bevacizumab; Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Lawrence Blaszkowsky
• Organization: Massachusetts General Hospital

lblaszkowsky@partners.org

6177244637

Study Officials

• Lawrence S. Blaszkowsky, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Physician

Study Record Dates

• First Submitted: March 24, 2006
• First Posted: March 28, 2006
• Study Start: May 1, 2006
• Primary Completion: April 1, 2010
• Study Completion: July 1, 2011
• Last Updated: May 10, 2017
• Results First Posted: May 10, 2017

Record last verified: 2017-03

Locations

US (3)