Weekly vs. Every 2 Week vs. Every 3 Week Administration of ABI-007 (Abraxane)/Bevacizumab Combination in Metastatic Breast Cancer

Breast Neoplasms Clinical Trial

Official title:

A Phase II Study of Weekly Versus Every 2-week Versus Every 3-week Administration of ABI-007 (Abraxane) in Combination With Bevacizumab in Women With Metastatic Breast Cancer.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00281528
• Other study ID #: CA023
• Status: Terminated
• Phase: Phase 2
• Start date: February 1, 2006
• Est. completion date: March 1, 2011

Study information

• Verified date: November 2019
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a multi-center, open-label, randomized Phase II study in previously untreated patients with metastatic breast cancer to evaluate the antitumor activity and safety of weekly dose-dense ABI-007 (Abraxane) compared to 2-weekly regimen vs the standard 3-weekly infusion. All patients will also receive concurrent bevacizumab.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 208
• Est. completion date: March 1, 2011
• Est. primary completion date: July 1, 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Pathologically confirmed adenocarcinoma of the breast.

• Stage IV disease

• Measurable disease

• Patients must not be a candidate for Herceptin therapy

• At least 4 weeks since radiotherapy, with full recovery. The measurable disease must be completely outside the radiation portal or there must be pathologic proof of progressive disease within the radiation portal.

• At least 4 weeks since major surgery, with full recovery.

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

• Female >18 years of age.

• Patient has the following blood counts at Baseline:

Absolute neutrophil count = 1.5 x 10^9cells/L; platelets = 100 x 10^9 cells/L; hemoglobin = 9 g/dL.

• Patient has the following blood chemistry levels at Baseline: Aspartate transaminase (AST or SGOT), alanine aminotransferase (ALT or SGPT) = 2.5x upper limit of normal range (ULN); total bilirubin = ULN; creatinine = 1.5 mg/dL.

• If female of childbearing potential, pregnancy test is negative within 72 hours of first dose of study drug.

• If fertile, the patient agrees to use an effective method to avoid pregnancy for the duration of the study.

• Informed consent has been obtained.

Exclusion Criteria:

• Prior neo-adjuvant or adjuvant chemotherapy is allowed, and patients must have recovered from the acute toxicity of such therapies. No prior therapy for metastatic disease is allowed. If a taxane was part of the adjuvant regimen, at least 12 months should have passed from completion of taxane regimen to relapse. If a non-taxane-based adjuvant therapy was administered, at least 6 months should have passed from completion to relapse.

• Concurrent immunotherapy or hormonal therapy.

• Parenchymal brain metastases, including leptomeningeal involvement.

• Inadequately controlled hypertension (defined as blood pressure of > 150/100 mmHg) or New York Heart Association (NYHA) Grade 2 or greater congestive heart failure.

• Any prior history of hypertensive crisis or hypertensive encephalopathy.

• History of myocardial infarction or unstable angina within 6 months prior to study enrollment.

• History of stroke or transient ischemic attack within 6 months prior to study enrollment.

• Significant vascular disease (e.g., aortic aneurysm, aortic dissection).

• Symptomatic peripheral vascular disease.

• Evidence of bleeding diathesis or coagulopathy.

• History of abdominal fistula, gastrointestinal perforation, or intra- abdominal abscess within 6 months prior to study enrollment.

• Proteinuria at screening as demonstrated by either: - Urine protein:creatinine (UPC) ratio > 1.0 at screening OR - Urine dipstick for proteinuria = 2+ (patients discovered to have = 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate = 1g of protein in 24 hours to be eligible).

• Known hypersensitivity to any component of bevacizumab.

• Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to first dose.

• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to first dose, anticipation of need for major surgical procedure during the course of the study. Serious, non-healing wound, ulcer, or bone fracture. Serious intercurrent medical or psychiatric illness, including serious active infection.

• History of other malignancy within the last 5 years which could affect the diagnosis or assessment of breast cancer.

• Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study.

• Pregnant or nursing women.

• Sensory neuropathy of > Grade 1 at baseline.

Related Conditions & MeSH terms

• Breast Neoplasms
• Neoplasm Metastasis
• Neoplasms

Intervention

Drug:
• ABI-007 (Abraxane)
30 minute infusions
• bevacizumab
infusions

Locations

Country	Name	City	State
Puerto Rico	Metropolitan Oncology Center	San Juan
United States	Peachtree Hematology & Oncology Associates	Atlanta	Georgia
United States	TX Oncology, PA	Austin	Texas
United States	Greater Baltimore Medical Center	Baltimore	Maryland
United States	Harbor View Cancer Center	Baltimore	Maryland
United States	Division of Hematology/Oncology University of Alabama at Birmingham	Birmingham	Alabama
United States	Boston Medical Center Moakley Building, Solomont Center for Hematology & Medical Oncology	Boston	Massachusetts
United States	Palm Beach Institute of Hematology and Oncology	Boynton Beach	Florida
United States	Oncology Associates of Bridgeport	Bridgeport	Connecticut
United States	Rosewell Park Cancer Institute Elm & Carlton Carlton Building	Buffalo	New York
United States	Medical Oncology Aultman Hospital	Canton	Ohio
United States	Family Cancer Center	Collierville	Tennessee
United States	Drs. Forte, Schleidere, & Attas, PA	Englewood	New Jersey
United States	Front Range Cancer Specialists	Fort Collins	Colorado
United States	California Oncology of the Central Valley	Fresno	California
United States	Glendale Memorial Hospital & Health Center	Glendale	California
United States	Memorial Cancer Institute/Breast Cancer Center	Hollywood	Florida
United States	Florida Cancer Institute	Hudson	Florida
United States	Tennessee Cancer Specialists	Knoxville	Tennessee
United States	Hematology Oncology Associates	Lake Worth	Florida
United States	Medical Specialist of the Palm Beaches, Inc	Lake Worth	Florida
United States	Cancer Centers of Southwest Oklahoma Research	Lawton	Oklahoma
United States	Little Rock Hematology Oncology Associates	Little Rock	Arkansas
United States	Saint Barnabas Medical Center	Livingston	New Jersey
United States	Monmouth Medical Center	Long Branch	New Jersey
United States	Northwest Georgia Oncology Centers, PC	Marietta	Georgia
United States	Beth Israel Comprehensive Cancer Center	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	NYU Clinical Cancer Center	New York	New York
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	North Shore Medical Cancer Center	Peabody	Massachusetts
United States	Virginia Commonwealth University Medical Oncology	Richmond	Virginia
United States	St. John's Mercy Medical Center	Saint Louis	Missouri
United States	Gulfcoast Oncology Associates	Saint Petersburg	Florida
United States	South Texas Oncology & Hematology Clinical Research Dept.	San Antonio	Texas
United States	Maine Center for Cancer Medicine & Blood Disorders	Scarborough	Maine
United States	Swedish Cancer Institute	Seattle	Washington
United States	Center of Hope for Cancers and Blood	Stockbridge	Georgia
United States	Marion L. Shepard Cancer Center	Washington	North Carolina
United States	Abington Hematology Oncology	Willow Grove	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (2)

Conlin AK, Seidman AD, Bach A, Lake D, Dickler M, D'Andrea G, Traina T, Danso M, Brufsky AM, Saleh M, Clawson A, Hudis CA. Phase II trial of weekly nanoparticle albumin-bound paclitaxel with carboplatin and trastuzumab as first-line therapy for women with — View Citation

Seidman AD, Conlin AK, Bach A, Moynahan ME, Lake D, Forero A, Wright GS, Hackney MH, Clawson A, Norton L, Hudis CA. Randomized phase II trial of weekly vs. every 2 weeks vs. every 3 weeks nanoparticle albumin-bound paclitaxel with bevacizumab as first-line chemotherapy for metastatic breast cancer. Clin Breast Cancer. 2013 Aug;13(4):239-246.e1. doi: 10.1016/j.clbc.2013.02.008. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Percentage of Participants Confirmed Complete Response (CR) or Partial Response (PR) Based on Response Evaluation Criteria In Solid Tumors (RECIST v1.0)	Using the RECIST response criteria version 1.0, the percent of participants achieving either a complete response (CR) defined as the disappearance of all known disease and no new sites or disease related symptoms confirmed at least 4 weeks after initial documentation or partial response (PR) defined as at least a 30% decrease in the sum of the longest diameters of target lesions and no progression in non-target lesions based on confirmed responses from the investigator assessment of best overall response during study treatment.	Up to 43 months
Primary	Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC) as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3)	Myelosuppression is a decrease in the ability of the bone marrow to produce blood cells. The lowest measured (nadir) ANC counts were graded using NCI CTCAE version 3: Grade 0 = within normal limits; Grade 1 = < lower limit of normal - 75.0*10^9L; Grade 2 = <1.5 - 1.0*10^9L; Grade 3 = <1.0 - 0.5*10^9L; Grade 4 = <0.5*10^9L	up to 54 months
Primary	Participant Counts of the Most Severe Grade for White Blood Cells (WBC) as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3)	Myelosuppression is a decrease in the ability of the bone marrow to produce blood cells. The lowest measured (nadir) WBC counts were graded using NCI CTCAE version 3: Grade 0 = within normal limits; Grade 1 = < lower limit of normal -3.0*10^9/L; Grade 2 = <3.0 - 2.0*10^9/L; Grade 3 = <2.0 - 1.0*10^9/L; Grade 4 = <1.0*10^9/L	up to 54 months
Primary	Participant Counts of the Most Severe Grade for Platelet Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3)	Myelosuppression is a decrease in the ability of the bone marrow to produce blood cells. The lowest measured (nadir) platelet counts were graded using NCI CTCAE version 3: Grade 0 = within normal limits; Grade 1 = < lower limit of normal - 75.0*10^9/L; Grade 2 = <75.0 - 50.0*10^9/L; Grade 3 = <50.0 - 25.0*10^9/L; Grade 4 = <25.0*10^9/L	up to 54 months
Primary	Participant Counts of the Most Severe Grade for Hemoglobin Levels as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3)	Myelosuppression is a decrease in the ability of the bone marrow to produce blood cells. The lowest measured (nadir) hemoglobin levels were graded using NCI CTCAE version 3: Grade 0 = within normal limits; Grade 1 = < lower limit of normal - 100g/L; Grade 2 = <100 - 80g/L; Grade 3 = <80 - 65g/L; Grade 4 = <65g/L	up to 54 months
Primary	The Number of Participants With at Least One Dose Reduction for ABI-007	Participants with at least one dose reduction for ABI-007. ABI-007 (Abraxane) dose could be reduced according to protocol guidelines if the participant was experiencing toxicities. Participants were allowed two ABI-007 (Abraxane) dose reductions during the course of the trial. This outcome is considered to be both a safety and an efficacy outcome.	Up to 53 months
Primary	The Number of Participants With at Least One Dose Delay for ABI-007	Participants with at least one dose delay for ABI-007. Treatment delays of no longer than 2 weeks allowed participants to recovery from acute toxicity. If treatment was delayed beyond 2 weeks, continuing treatment on protocol was at the physician's discretion, based upon the best interests of the participant. This outcome is considered to be both a safety and an efficacy outcome.	Up to 53 months
Primary	The Number of Participants With a Dose Interruption of ABI-007	Number of participants who interrupted (omitted) a dose at some point in the treatment period. This outcome is considered to be both a safety and an efficacy outcome.	Up to 53 months
Secondary	Percentage of Participants With Stable Disease for = 16 Weeks, or Complete or Partial Overall Response (i.e., Total Response) Based on Response Evaluation Criteria In Solid Tumors (RECIST v1.0)	Using Response Evaluation Criteria in Solid Tumors (RECIST v1.0), the percentage of participants achieving either; A complete response (CR) defined as the disappearance of all known disease and no new sites or disease related symptoms confirmed at least 4 weeks after initial documentation or; A partial response (PR) defined as at least a 30% decrease in the sum of the longest diameters of target lesions and no progression in non-target lesions or; Stable disease (SD) defined as neither sufficient shrinkage to qualify for PR or sufficient increase to qualify for progressive disease.	Up to 43 months (until progressed)
Secondary	Kaplan Meier Estimate for Time to Disease Progression (TTP)	Time to progression was defined as the time from the first dose of study drug to the start of progression. Participants that did not have progression were censored at the last known time the patient was evaluated for progression. Participants that initiate other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated.; Progressive disease was defined as at least a 20% increase in the sum of the longest diameters of target lesions; or the appearance of one or more new lesions; or the unequivocal progression of a non-target lesion.	Up to 43 months (until progressed)
Secondary	Kaplan Meier Estimate for Duration of Response	Duration of response was defined as the time from response to the time of disease progression for participants who achieve an objective confirmed complete (CR) or partial overall response (PR). Disease progression is based on the assessments by the investigator. Participants who did not have disease progression following a confirmed complete or partial target response were censored at the last known time that the participant was evaluated for response	Up to 43 months (until progressed)
Secondary	Kaplan Meier Estimate for Participant Survival	Participant survival was summarized using Kaplan-Meier estimate of the time of first dose of study drug to the last known time that the participant was alive. Participants that were alive at the end of follow-up would be censored at the last known time that the patient was alive.	Up to 56 months
Secondary	Kaplan Meier Estimate for Progression-Free Survival (PFS)	PFS was defined as the time from the first dose of study drug to the start of progression or patient death (any cause) whichever occurred first. Participants that did not have progression or have not died were censored at the last known time the participant was progression free. Participants that initiate other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated.	up to 56 months