Study of Biweekly Capecitabine Dosing With Bevacizumab for the Treatment of Metastatic Breast Cancer Based Upon the Norton-Simon Mathematical Model

NCT00468585 | Completed Phase 1 Results DMC

• 1 other identifier: 05-030
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 5

Brief Summary

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:

1. 1.What are the side effects of bevacizumab and capecitabine when given in this different schedule and how often do they occur?
2. 2.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?

Conditions

Breast Cancer

Keywords

Breast cancer; Metastatic breast cancer; Breast; Metastatic

Outcome Measures

Primary Outcomes (1)

• Overall Objective Response

  This is defined as the percentage of patients who achieve either an objective complete or partial target lesion response that is confirmed based on the RECIST criteria.

  2 years

Study Arms (1)

1 Capecitabine and Bevacizumab

EXPERIMENTAL

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; Drug: Bevacizumab

Interventions

Capecitabine DRUG

1 Capecitabine and Bevacizumab

Bevacizumab DRUG

1 Capecitabine and Bevacizumab

Eligibility Criteria

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

You may qualify if:

• Patient (male or female) with diagnosis of invasive adenocarcinoma of the breast confirmed at MSKCC either by histology or cytology.
• Clinical evidence of metastatic breast cancer, non-amenable to surgery or radiation therapy with curative intent.
• Presence of at least one measurable metastatic lesion according to the RECIST criteria which has not been irradiated (i.e. newly arising lesions in previously irradiated areas are accepted). Ascites, pleural effusion, and bone metastases are not considered measurable. Minimum indicator lesion size: greater than or equal to 10 mm measured by spiral CT or greater than or equal to 20 mm measured by conventional techniques.
• Any number of prior endocrine or biologic therapies is permitted on this trial. In addition, patients may be untreated in the metastatic setting or have received any number of prior cytotoxic regimens. All previous chemotherapy must have been discontinued at least 3 weeks prior to study entry. All acute toxic effects (excluding alopecia or neurotoxicity) of any prior therapy must have resolved to NCI CTC (Version 3) Grade less than or equal to 1.
• Endocrine therapy with an aromatase inhibitor, SERM (ie, tamoxifen) or fulvestrant is permitted within 4 weeks of study entry, however concurrent therapy with these drugs is not acceptable.
• ECOG performance status of 0, 1 or 2.
• Patients must be either HER2-negative or HER2-positive and no longer a candidate for trastuzumab therapy. HER2-negative is defined as 0 or 1+ staining on immunohistochemistry or FISH negative for gene amplification. HER2-positive is defined as 3+ staining on immunohistochemistry or FISH positive for gene amplification.
• Age greater than or equal to 18 years old.
• Baseline laboratory data within the following limits:
• Absolute neutrophil count (ANC) \>1.5 x 10\^9/L
• Platelets \> 100 x 10\^9/L
• Estimated creatinine clearance greater than or equal to 50 ml/min by - Cockcroft-Gault equation
• Total serum bilirubin \<1.5 x upper normal limit
• ALT, AST \< 2.5x upper normal limit (or \<5x upper normal limit in the case of liver metastases)
• Alkaline phosphatase \< 2.5x upper normal limit (or \>5x upper normal limit in the case of liver metastases or \>10x upper normal limit in the case of bone disease)

You may not qualify if:

• Pregnant or nursing women may not participate. Patients of reproductive potential may not participate unless they have agreed to use an effective method of contraception and to continue contraception for 30 days from the date of the last study drug administration. Postmenopausal woman must be amenorrheic for at least 12 months to be considered of nonchildbearing potential.
• Life expectancy \< 3 months.
• Serious, uncontrolled, concurrent infection.
• Any prior fluoropyrimidine therapy with the exception of adjuvant administration. Adjuvant fluoropyrimidine containing therapy must be completed at least 6 months prior to enrollment.
• Prior severe reaction to fluoropyrimidine therapy, or known hypersensitivity to 5-fluorouracil. A history of DPD deficiency will exclude patients from the trial.
• Completion of previous chemotherapy regimen \<3 weeks prior to the start of study treatment.
• Prior adjuvant hormonal therapy is permitted. Use of an aromatase inhibitor, anti-estrogen or fulvestrant must be discontinued prior to treatment start.
• Biologic therapy (eg, bevacizumab,trastuzumab) for the treatment of metastatic disease must be discontinued \>3 weeks from the start of protocol treatment.
• HER2-positive patients who are candidates for treatment with trastuzumab are excluded from this trial as the concurrent use of trastuzumab may confound study results.
• History of prior malignancy with the following exceptions: adequately treated basal cell or squamous cell carcinoma, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission (with no evidence of disease) for more than five years.
• Non-malignant systemic disease (cardiovascular, renal, hepatic etc) that would preclude any of the study therapy drugs. Specifically excluded are the following cardiac conditions:
• Inadequately controlled hypertension (defined as blood pressure of \>150/100 mmHg on antihypertensive medications)
• Any prior history of hypertensive crisis or hypertensive encephalopathy
• New York Heart Association (NYHA) Class II or greater congestive heart failure
• History of myocardial infarction or unstable angina within 6 months

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (5)

Memorial Sloan-Kettering at Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan-Kettering Cancer Center at Commack

Commack, New York, 11725, United States

Location

Memorial Sloan-Kettering Cancer Center 1275 York Avenue

New York, New York, 10021, United States

Location

Memorial Sloan-Kettering Cancer Center at Mercy Medical Center

Rockville Centre, New York, 11570, United States

Location

Memorial Sloan-Kettering Cancer Center at Phelps Memorial Hospital Center

Sleepy Hollow, New York, 10591, United States

Location

Related Links

• Related Info

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis

Interventions

Capecitabine; Bevacizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Tiffany Traina
• Organization: Memorial Sloan Kettering Cancer Center

trainat@mskcc.org

646-888-4558

Study Officials

• Tiffany Traina, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2007
• First Posted: May 3, 2007
• Study Start: June 1, 2005
• Primary Completion: April 1, 2011
• Study Completion: April 1, 2011
• Last Updated: January 22, 2016
• Results First Posted: January 22, 2016

Record last verified: 2015-12

Locations

US (5)