Clinical trial NCT00203411: Bevacizumab Plus Capecitabine (Xeloda) in Patients With Untreated Metastatic Colorectal Cancer
Official title: A Phase II Trial to Evaluate the Efficacy and Safety of Bevacizumab in Combination With Capecitabine (Xeloda) in Frail Patients With Untreated Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
Lead sponsor: Translational Oncology Research International
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2005-09-20
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety and effectiveness of the bevacizumab and capecitabine combination in frail patients with untreated metastatic colorectal cancer.

Detailed description: The study will evaluate the tolerability, safety, and feasibility of combination bevacizumab and capecitabine in a small number of frail patients with metastatic colorectal cancer who have a compromised performance status. Preclinical studies suggest that the combination of chemotherapy and anti-angiogenic therapy offer an increased anti-tumor effect compared with either treatment alone.

Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically proven adenocarcinoma of the colon at first diagnosis
* Stage IV disease, with at least one measurable lesion according to the RECIST criteria
* Eastern Cooperative Oncology Group (ECOG) performance status 2
* No prior chemotherapy for metastatic colorectal cancer
* Prior adjuvant chemotherapy is permitted.
* At least 28 days since prior surgery
* If female of childbearing potential, pregnancy test is negative and willing to use effective contraception while on treatment and for at least 3 months thereafter.
* Required laboratory values:

  * Absolute neutrophil count \> 1.5 x 10\^9/L
  * Hemoglobin \> 9.0 g/dL
  * Platelet count \> 100 x 10\^9/L
  * Creatinine \< 2.0 mg/dL
  * Total bilirubin \< 1.5 x upper limit of normal (ULN) (Patients with documented Gilbert's syndrome are eligible.)
  * Alkaline phosphatase and AST/ALT within the following parameters. In determining eligibility, the more abnormal of the two values (AST or ALT) should be used:

    * Alkaline phosphate and AST/ALT \< or = ULN
    * Alkaline phosphate \> 1x but \< or = 2.5x and AST/ALT \< or = ULN
    * Alkaline phosphate \> 2.5x but \< or = 5x and AST/ALT \< or = ULN
    * Alkaline phosphate \< or = ULN and AST/ALT \> 1x but \< or = 1.5x
    * Alkaline phosphate \> 1x but \< or = 2.5 x and AST/ALT \> 1x but \< or = 1.5x
    * Alkaline phosphate \< or = ULN and AST/ALT \> 1x but \< or = 2.5x

Exclusion Criteria:

* Prior chemotherapy for metastatic colorectal cancer
* Prior treatment with an anti-angiogenic agent
* Concurrent therapy with any other non-protocol anti-cancer therapy
* Current or prior history of central nervous system or brain metastases
* Presence of neuropathy \> grade 2 (NCI-Common Toxicity Criteria (CTC) version 3.0) at baseline
* Presence of any non-healing wound, fracture, or ulcer, or the presence of clinically significant (\> grade 2) peripheral vascular disease
* History of any other malignancy within the past 5 years, with the exception of non-melanoma skin cancer or carcinoma-in-situ of the cervix
* Clinically significant cardiovascular disease (e.g., blood pressure \[BP\] \> 150/100, myocardial infarction or stroke within the past 6 months, unstable angina, New York Heart Association (NYHA) Grade II or greater congestive heart failure, or serious cardiac arrhythmia requiring medication
* Active peptic ulcer disease, inflammatory bowel disease, or other gastrointestinal condition increasing the risk of perforation; history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning therapy
* Active infection requiring parenteral antimicrobials
* The presence of any other medical or psychiatric disorder that, in the opinion of the treating physician, would contraindicate the use of the drugs in this protocol or place the subject at undue risk for treatment complications
* Inability to comply with the study protocol or follow-up procedures
* Pregnancy or lactation
* A history of a severe hypersensitivity reaction to bevacizumab, or capecitabine or other drugs formulated with polysorbate 80.
* Evidence of bleeding diathesis or coagulopathy.
* Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, or anticipation of the need for a major surgical procedure during the course of the study; minor surgical procedure, fine needle aspiration or core biopsy within 7 days prior to Day 0
* Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study
* Unstable angina
* Urine protein creatinine ratio greater than or equal to 1.
* Therapeutic anticoagulation with oral anticoagulation medications, specifically coumarins

Primary outcomes:
measure: Time to Disease Progression
timeFrame: 12 months
measure: Number of Subjects Requiring Dose Modifications
timeFrame: 3 months
Secondary outcomes:
measure: Response Rates
timeFrame: every 21 days up to 12 months
measure: Quality of Life of Patients
timeFrame: Baseline, Cycle 2, and End of Study
Other outcomes:
Locations:
city: Alhambra
country: United States
facility: Central Hematology Oncology Medical Group, Inc.
state: California
city: Bakersfield
country: United States
facility: Comprehensive Blood and Cancer Center
state: California
city: Fullerton
country: United States
facility: Virginia K. Crosson Cancer Center
state: California
city: Long Beach
country: United States
facility: Pacific Shores Medical Group
state: California
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: Northridge
country: United States
facility: North Valley Hematology/Oncology Medical Group
state: California
city: Oxnard
country: United States
facility: Ventura County Hematology-Oncology Specialists
state: California
city: Pomona
country: United States
facility: Wilshire Oncology Medical Group, Inc.
state: California
city: Redondo Beach
country: United States
facility: Cancer Care Associates Medical Group, Inc.
state: California
city: Santa Barbara
country: United States
facility: Santa Barbara Hematology Oncology Medical Group, Inc.
state: California
city: Santa Maria
country: United States
facility: Central Coast Medical Oncology Corporation
state: California
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
Study officials:
affiliation: University of California, Los Angeles
name: Arash Naeim, MD, PhD
role: STUDY_CHAIR
affiliation: University of California, Los Angeles
name: Randy Hecht, MD
role: STUDY_CHAIR
References: