Study of Biweekly Capecitabine Dosing With Bevacizumab for the Treatment of Metastatic Breast Cancer Based Upon the Norton-Simon Mathematical Model
The purpose of this study is to find out what effects (both good and bad) that capecitabine has on you and your breast cancer when given in a novel schedule in combination with the antibody therapy, bevacizumab. Capecitabine (Xeloda®) is an anticancer drug that was approved by FDA in 1998 for treating metastatic breast cancer. Capecitabine is a pill that blocks the way cancer cells multiply and grow. Usually, this medicine is taken twice a day for fourteen days in a row.
Patients then get a break from the drug for seven days. With this schedule and usual dose, some patients on capecitabine have experienced side effects that interfered with their daily comfort.Different doses and schedules of capecitabine have been studied in animal studies and in people with colon cancer. Mathematic modeling has been used to better understand these results.Information from these experiments leads us to ask if 7 days of treatment with capecitabine followed by a 7-day break is both safer and more active against breast cancer. The study you are considering is a first step in this direction and is designed to demonstrate both safety and activity.
Bevacizumab is a biologic therapy that targets the growth of blood vessels which tumors need to grow. Women whose breast cancer spread to other parts of their bodies lived longer without their cancers growing when they were treated with bevacizumab and chemotherapy. Bevacizumab was tested with the 14-day/7-day schedule of capecitabine. These two medicines are safe when given together and seem to work better against breast cancer than capecitabine alone.
This study is designed to answer the questions:
- What are the side effects of bevacizumab and capecitabine when given in this different schedule and how often do they occur?
- When given in this schedule, does capecitabine with bevacizumab help treat breast cancer that has spread or continues to grow despite being treated by other chemotherapy drugs before?
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Multicenter, Phase I/II Study of Every Other Week Capecitabine Dosing With Bevacizumab for the Treatment of Metastatic Breast Cancer Based Upon the Norton-Simon Mathematical Model|
- The primary endpoint of the phase I portion of the trial is the MTD of biweekly capecitabine. [ Time Frame: in 2 years ] [ Designated as safety issue: Yes ]
- Secondary efficacy endpoints of the phase II study include clinical benefit (CR+PR+SD, >6 months), time to tumor progression, progression free survival and duration of response associated with the combination of biweekly capecitabine and bevacizumab. [ Time Frame: in 2 years ] [ Designated as safety issue: No ]
- A secondary safety endpoint is to determine the toxicity rate associated with the combination of biweekly capecitabine and bevacizumab. [ Time Frame: each study visit for the duration of their participation in the study. ] [ Designated as safety issue: Yes ]
|Study Start Date:||June 2005|
|Study Completion Date:||April 2011|
|Primary Completion Date:||April 2011 (Final data collection date for primary outcome measure)|
Experimental: 1 Capecitabine and Bevacizumab
The Phase II trial has a Simon mini-max two-stage design. Twenty-seven patients will be enrolled to the first stage of the Phase II trial, with a target accrual of 40 patients. The treatment dose of capecitabine as determined in the Phase I portion of this trial will be administered orally in two divided doses daily on Days 1 through 7 and Days 15 through 21 in a 28 day cycle. Phase II patients will receive bevacizumab 10 mg/kg intravenously every 2 weeks concurrently with oral capecitabine. Patients will be evaluated for toxicity between Days 3 to 5 (complete blood count only), Day 8, Day 15, and Day 22 during cycle #1. Thereafter, toxicity will be assessed on Days 1 and 15. Efficacy will be assessed with every other week physical examination and radiographic scans of measurable disease every 12 weeks.
Drug: Capecitabine and Bevacizumab
In the Phase I portion of the study, a standard three patient per cohort dose escalation scheme will be used, treating between 6 and 36 patients with biweekly capecitabine monotherapy. There will be no intrapatient dose escalation. The starting dose of capecitabine is 1,500 mg twice daily. Capecitabine will be administered orally in two divided doses daily on Days 1 through 7 and Days 15 through 21 in a 28 day cycle.
The Phase II trial has a Simon mini-max two-stage design. The treatment dose of capecitabine as determined in the Phase I portion of this trial will be administered orally in two divided doses daily on Days 1 through 7 and Days 15 through 21 in a 28 day cycle. Phase II patients will receive bevacizumab 10 mg/kg intravenously every 2 weeks concurrently with oral capecitabine. Patients will be evaluated for toxicity between Days 3 to 5.
A. Primary Objectives:
• To estimate the efficacy of every other week capecitabine and bevacizumab in patients with metastatic breast cancer in terms of overall response rate (complete response (CR) + partial response (PR)) when administered at the MTD of capecitabine determined by the phase I portion of this trial.
B. Secondary Objectives:
- To estimate secondary efficacy endpoints of this combination including clinical benefit (CR+PR+SD > 6 months), time to tumor progression (TTP), progression free survival (TTP) and duration of response.
- To evaluate toxicity rates associated with this capecitabine schedule in combination with bevacizumab using the NCI CTC (version 3) and the Hand-Foot Syndrome Grading Scale developed by Roche Laboratories, Inc.
- To evaluate the pharmacogenetics of capecitabine in breast cancer patients by assessing the impact of specific candidate SNPs on toxicity and/or response.
|United States, New Jersey|
|Memorial Sloan-Kettering at Basking Ridge|
|Basking Ridge, New Jersey, United States, 07920|
|United States, New York|
|Memorial Sloan-Kettering Cancer Center at Commack|
|Commack, New York, United States, 11725|
|Memorial Sloan-Kettering Cancer Center 1275 York Avenue|
|New York, New York, United States, 10021|
|Memorial Sloan-Kettering Cancer Center at Mercy Medical Center|
|Rockville Centre, New York, United States, 11570|
|Memorial Sloan-Kettering Cancer Center at Phelps Memorial Hospital Center|
|Sleepy Hollow, New York, United States, 10591|
|Principal Investigator:||Tiffany Traina, MD||Memorial Sloan-Kettering Cancer Center|