A Trial of Paclitaxel and Bevacizumab vs. Gemcitabine, Paclitaxel, and Bevacizumab in Advanced Breast Cancer

• ClinicalTrials.gov Identifier: NCT00320541
• Recruitment Status: Completed
• First Posted: May 3, 2006
• Results First Posted: July 27, 2010
• Last Update Posted: July 22, 2013
• Sponsor: Eli Lilly and Company
• Collaborator: Genentech, Inc.
• Information provided by (Responsible Party): Eli Lilly and Company

Study Description

Brief Summary:

This study will compare the cancer response to both treatments for locally advanced or metastatic breast cancer

Condition or disease	Intervention/treatment	Phase
Breast Cancer	Drug: gemcitabine; Drug: paclitaxel; Drug: bevacizumab	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 187 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Phase II Trial of Paclitaxel and Bevacizumab Versus Gemcitabine, Paclitaxel, and Bevacizumab as First Line Treatment for Locally Advanced or Metastatic Breast Cancer
• Study Start Date: May 2006
• Actual Primary Completion Date: April 2009
• Actual Study Completion Date: August 2012

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: paclitaxel plus bevacizumab (PB); paclitaxel 90 milligrams per meter squared (mg/m2) administered intravenously (IV) on days 1, 8, 15 every 28 days followed by bevacizumab 10 milligrams per kilogram (mg/kg) administered IV on days 1 and 15 every 28 days	Drug: paclitaxel; 90 mg/m2, IV, day 1, day 8 and day 15 every 28 days until complete response, disease progression or unacceptable toxicity; Other Name: Taxol; Drug: bevacizumab; 10 mg/kg, IV, day 1 and day 15 every 28 days until complete response, disease progression or unacceptable toxicity; Other Name: Avastin
Experimental: paclitaxel plus bevacizumab plus gemcitabine (PB+G); paclitaxel 90 milligrams per meter squared (mg/m2) administered intravenously (IV) on days 1, 8, 15 every 28 days followed by gemcitabine 1500 mg/m2 IV on days 1 and 15 every 28 days followed by bevacizumab 10 milligrams per kilogram (mg/kg) administered IV on days 1 and 15 every 28 days	Drug: gemcitabine; 1500 mg/m2, IV day 1 and day 15 every 28 days until complete response, disease progression or unacceptable toxicity; Other Names: LY188011; Gemzar; Drug: paclitaxel; 90 mg/m2, IV, day 1, day 8 and day 15 every 28 days until complete response, disease progression or unacceptable toxicity; Other Name: Taxol; Drug: bevacizumab; 10 mg/kg, IV, day 1 and day 15 every 28 days until complete response, disease progression or unacceptable toxicity; Other Name: Avastin

Outcome Measures

Primary Outcome Measures :

1. Overall Response Rate (ORR) [ Time Frame: baseline & every 2 cycles (approximately 8 weeks) of treatment to measured progressive disease (PD) & post-therapy until PD or other therapy initiated (up to 35 months) ]
   Response defined per Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR)=disappearance of all target lesions; Partial Response (PR)=30% decrease in sum of longest diameter of target lesions; Progressive Disease=20% increase in sum of longest diameter of target lesions; Stable Disease=small changes that do not meet above criteria. ORR was defined as the proportion of participants who achieved a best response of either CR or PR. ORR=number of participants with CR or PR/number of participants qualified for tumor response analysis (per-protocol population).

Secondary Outcome Measures :

1. Progression-free Survival (PFS) [ Time Frame: baseline to measured progressive disease or death up to 35 months (tumor assessments were performed every 2 cycles during study therapy; every 2 months during post-therapy until disease progression or new anticancer treatment initiated) ]
   PFS was measured from date of randomization to first date of disease progression or death from any cause. For participants not known to have died or had disease progression as of data-inclusion cut-off date, PFS duration was censored at date of last study visit prior to data-inclusion cut-off date.
2. Overall Survival [ Time Frame: baseline to death from any cause (up to 35 months) ]
   Overall survival was measured from date of randomization to date of death from any cause. For participants not known to have died as of data-inclusion cut-off date, overall survival duration was censored at date of last study visit prior to the data cut-off date.
3. Total Functional Assessment of Cancer Therapy -Breast (FACT-B): Change From Baseline to End of Therapy [ Time Frame: Baseline through 30 days post therapy follow-up (up to 35 months) ]
   FACT-B measures the following domains of health-related quality of life (HR-QL): physical well-being (PWB), social/family well-being (SFWB), emotional well-being (EWB), functional well-being (FWB), & additional concerns of breast cancer (BCS). Total FACT-B scores range from 0-144, with higher scores representing better HR-QOL. Minimally important differences estimates obtained for FACT-B is 7-8 points. FACT-B was assessed at baseline (prior to start of Cycle 1 [Day 1]), prior to start of each subsequent cycle (approximately every 4 weeks) during therapy, through 30-day post therapy follow-up.
4. Physical Well Being (PWB) Subscale: Change From Baseline to End of Therapy [ Time Frame: Baseline through 30 days post therapy follow-up (up to 35 months) ]
   The PWB subscale of FACT-B measures physical well-being. Total PWB scores range from 0 to 28, with higher scores representing better HR-QOL. FACT-B was assessed at baseline (prior to start of Cycle 1 [Day 1]), then prior to start of each subsequent cycle (approximately every 4 weeks) during therapy, through 30-day post therapy follow-up.
5. Social/Family Well Being (SFWB) Subscale: Change From Baseline to End of Therapy [ Time Frame: Baseline through 30 days post therapy follow-up (up to 35 months) ]
   The SFWB subscale of FACT-B measures social/family well-being. Total SFWB scores range from 0 to 28, with higher scores representing better HR-QOL. FACT-B was assessed at baseline (prior to start of Cycle 1 [Day 1]), then prior to start of each subsequent cycle (approximately every 4 weeks) during therapy, through 30-day post therapy follow-up.
6. Emotional Well Being (EWB) Subscale: Change From Baseline to End of Therapy [ Time Frame: Baseline through 30 days post therapy follow-up (up to 35 months) ]
   The EWB subscale of FACT-B measures emotional well-being. Total EWB scores range from 0 to 24, with higher scores representing better HR-QOL. FACT-B was assessed at baseline (prior to start of Cycle 1 [Day 1]), then prior to start of each subsequent cycle (approximately every 4 weeks) during therapy, through 30-day post therapy follow-up.
7. Functional Well Being (FWB) Subscale: Change From Baseline to End of Therapy [ Time Frame: Baseline through 30 days post therapy follow-up (up to 35 months) ]
   The FWB subscale of FACT-B measures functional well-being. Total FWB scores range from 0 to 28, with higher scores representing better HR-QOL. FACT-B was assessed at baseline (prior to start of Cycle 1 [Day 1]), then prior to start of each subsequent cycle (approximately every 4 weeks) during therapy, through 30-day post therapy follow-up.
8. Breast Cancer Subscale (BCS): Change From Baseline to End of Therapy [ Time Frame: Baseline through 30 days post therapy follow-up (up to 35 months) ]
   The BCS subscale of FACT-B measures additional concerns of breast cancer . Total BCS scores range from 0 to 36, with higher scores representing better HR-QOL. Minimally important differences estimates obtained for BCS is 2-3 points. FACT-B was assessed at baseline (prior to start of Cycle 1 [Day 1]), then prior to start of each subsequent cycle (approximately every 4 weeks) during therapy, through 30-day post therapy follow-up.
9. Trial Outcome Index-Breast (TOI-B): Change From Baseline to End of Therapy [ Time Frame: Baseline through 30 days post therapy follow-up (up to 35 months) ]
   The TOI-B represents the total of the subscales PWB,FWB, and BCS. Total TOI-B scores range from 0 to 92, with higher scores representing better HR-QOL. Minimally important differences estimates obtained for TOI is 5-6 points. FACT-B was assessed at baseline (prior to start of Cycle 1 [Day 1]), then prior to start of each subsequent cycle (approximately every 4 weeks) during therapy, through 30-day post therapy follow-up.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Females diagnosed with breast cancer and the cancer has spread to distant areas of the breast or organs.
• Must be able to measure the disease by specific medical parameters
• May have received breast cancer treatment in the early stage of the disease
• May be restricted in physically strenuous activity but able to carry out light work.
• Must have adequate organ function as seen in blood test results.

Exclusion

Criteria:

• Cancer that has spread to the brain.
• Unstable heart problems
• Unstable high blood pressure.
• Breast cancer treatment after the disease has considered to spread to other areas or organs.
• Unable to agree with the requirements of the study

Contacts and Locations

Locations

United States, Arkansas

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Fayetteville, Arkansas, United States, 72703

United States, California

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La Jolla, California, United States, 92037

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Mission Hills, California, United States, 91345

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Santa Rosa, California, United States, 95403

United States, Colorado

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Denver, Colorado, United States, 80218

United States, Florida

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Fort Myers, Florida, United States, 33916

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Miami Beach, Florida, United States, 33140

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Miami, Florida, United States, 33136

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Orlando, Florida, United States, 32806

United States, Georgia

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Atlanta, Georgia, United States, 30322

United States, Illinois

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Springfield, Illinois, United States, 62703

United States, Indiana

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Muncie, Indiana, United States, 47303

United States, Kentucky

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Lexington, Kentucky, United States, 40536

United States, Michigan

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Southfield, Michigan, United States, 48075

United States, Missouri

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Chesterfield, Missouri, United States, 63017

United States, Montana

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Missoula, Montana, United States, 59807

United States, Ohio

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Akron, Ohio, United States, 44302

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Dayton, Ohio, United States, 45429

United States, Oklahoma

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Oklahoma City, Oklahoma, United States, 73104

United States, Pennsylvania

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Dunmore, Pennsylvania, United States, 18512

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Pittsburgh, Pennsylvania, United States, 15213

United States, Tennessee

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Knoxville, Tennessee, United States, 37916

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Memphis, Tennessee, United States, 38138

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Nashville, Tennessee, United States, 37203

United States, Texas

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Dallas, Texas, United States, 75237

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Lubbock, Texas, United States, 79415

United States, Virginia

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Richmond, Virginia, United States, 23230

United States, Washington

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Everett, Washington, United States, 98201

United States, Wisconsin

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Madison, Wisconsin, United States, 53717

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Milwaukee, Wisconsin, United States, 53226

Puerto Rico

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Ponce, Puerto Rico, 00716

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San Juan, Puerto Rico, 00935

Sponsors and Collaborators

Eli Lilly and Company

Genentech, Inc.

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST); Eli Lilly and Company

More Information

Additional Information:

Lilly Clinical Trial Registry 

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT00320541
• Other Study ID Numbers: 10663; B9E-US-S377 ( Other Identifier: Eli Lilly and Company )
• First Posted: May 3, 2006
• Results First Posted: July 27, 2010
• Last Update Posted: July 22, 2013
• Last Verified: July 2013

Keywords provided by Eli Lilly and Company:

Breast Cancer; Cancer of Breast; Cancer of the breast; Breast Neoplasms

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Gemcitabine; Paclitaxel; Bevacizumab; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antiviral Agents; Anti-Infective Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors