Phase II Trial of Weekly or Every 3-week Ixabepilone for Patients With Metastatic Breast Cancer

Metastatic Breast Cancer Clinical Trial

Official title:

Phase II Randomized Trial of Weekly and Every 3-week Ixabepilone in Metastatic Breast Cancer (MBC) Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00593827
• Other study ID #: CA163-132
• Secondary ID: USOR 06-106
• Status: Completed
• Phase: Phase 2
• First received: January 4, 2008
• Last updated: February 9, 2016
• Start date: May 2008
• Est. completion date: August 2010

Study information

• Verified date: February 2016
• Source: R-Pharm
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study was to determine the effects of the weekly regimen of ixabepilone dosing compared to the once every 3 week dosing regimen in participants with metastatic breast cancer.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 176
• Est. completion date: August 2010
• Est. primary completion date: August 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Has MBC that is measurable by RECIST or has nonmeasurable disease with serum CA27.29 (or CA15.3) = 50

• Has Human Epidermal Growth Factor Receptor 2 (HER2) negative breast cancer

• Prior chemotherapy is permitted with no limit on the number of prior regimens

• Two weeks or more have elapsed since last chemotherapy or radiation treatment

• Has an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0-2

• Is female, = 18 yrs of age

• Protocol defined appropriate laboratory values

• Negative pregnancy test within 7 calendar days prior to registration

• Has signed a patient informed consent

Exclusion Criteria:

• Had prior treatment with ixabepilone or other epothilones

• Has HER2+ disease

• Has a known, prior, severe (National Cancer Institute Common Terminology Criteria Adverse Events [NCI CTCAE] Grade 3-4) history of hypersensitivity reaction to a drug formulated in Cremophor ® EL (polyoxyethylated castor oil)

• Is receiving concurrent immunotherapy, hormonal therapy or radiation therapy

• Is receiving concurrent investigational therapy or has received such therapy within the past 30 days

• Has peripheral neuropathy > Grade 1

• Has evidence of central nervous system (CNS) involvement requiring radiation or steroid treatment. Participants with stable brain metastases who are off steroids at least 2 weeks are eligible

• Is pregnant or breast feeding

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• Ixabepilone
Injection, IV, Until progressive disease or intolerable toxicity Ixabepilone 16 mg/m^2 was administered as a 1-hour IV continuous infusion on Days 1, 8, and 15 in a 28-day cycle until progressive disease or intolerable toxicity.
• Ixabepilone
Injection, IV, Until progressive disease or intolerable toxicity Ixabepilone 40 mg/m^2 was administered as a 3-hour IV infusion on Day 1 of each 21-day cycle provided the subject met the retreatment criteria.

Locations

Country	Name	City	State
United States	New York Oncology Hematology, P.C.	Amsterdam	New York
United States	Texas Cancer Center	Arlington	Texas
United States	Texas Oncology-Central Austin Cancer Center	Austin	Texas
United States	Mamie Mcfaddin Ward Cancer Center Texas Oncology	Beaumont	Texas
United States	Texas Oncology	Bedord	Texas
United States	Birmingham Hematology & Oncology Associates Llc	Birmingham	Alabama
United States	Central Indiana Cancer Centers	Carmel	Indiana
United States	Maryland Oncology Hematology, P.A.	Columbia	Maryland
United States	Missouri Cancer Associates	Columbia	Missouri
United States	Baylor Sammons Cancer Ctr	Dallas	Texas
United States	Texas Cancer Center At Medical City	Dallas	Texas
United States	Texas Oncology	Dallas	Texas
United States	Texas Oncology Sammons Cancer Center	Dallas	Texas
United States	Texas Oncology/Methodist Charlton Cancer Ctr	Dallas	Texas
United States	Texas Cancer Center	Denton	Texas
United States	Regional Cancer Care	Durham	North Carolina
United States	Puget Sound Cancer Centers	Edmonds	Washington
United States	Texas Oncology	Fort Worth	Texas
United States	Texas Oncology	Garland	Texas
United States	Cancer Centers Of The Carolinas	Greenville	South Carolina
United States	Comprehensive Cancer Center Of Nevada	Henderson	Nevada
United States	Texas Oncology	Houston	Texas
United States	Florida Cancer Institute	Hudson	Florida
United States	Kansas City Cancer Center, Llc	Kansas City	Missouri
United States	Texas Oncology - Lake Vista Cancer Center	Lewisville	Texas
United States	Longview Cancer Center	Longview	Texas
United States	South Texas Cancer Center	Mcallen	Texas
United States	Texas Cancer Center Of Mesquite	Mesquite	Texas
United States	Texas Oncology, Pa	Midland	Texas
United States	Minnesota Oncology Hematology, P.A.	Minneapolis	Minnesota
United States	Hematology-Oncology Assoc. Of Northern Nj, Pa	Morristown	New Jersey
United States	Southwest Cancer Care	Murrieta	California
United States	Cancer Care & Hematology Specialists Of Chicagoland	Niles	Illinois
United States	Ocala Oncology Center	Ocala	Florida
United States	Cancer Centers Of Florida, P.A	Ocoee	Florida
United States	Texas Oncology - Odessa	Odessa	Texas
United States	Paris Regional Cancer Center Lab	Paris	Texas
United States	Hematology Oncology Associates	Phoenix	Arizona
United States	Raleigh Hematology Oncology Associates	Raleigh	North Carolina
United States	Interlakes Oncology & Hematology, P.C.	Rochester	New York
United States	Oncology & Hematology Associates Of Southwest Virginia, Inc.	Salem	Virginia
United States	New Mexico Cancer Care Associates	Santa Fe	New Mexico
United States	Puget Sound Cancer Centers	Seattle	Washington
United States	Northern Arizona Hematology & Oncology Associates	Sedona	Arizona
United States	Texas Cancer Center - Sherman	Sherman	Texas
United States	Cancer Care Northwest	Spokane	Washington
United States	Evergreen Hematology And Oncology	Spokane	Washington
United States	Arch Medical Services, Inc.	St. Louis	Missouri
United States	Texas Oncology Cancer Center - Sugar Land	Sugar Land	Texas
United States	Hope Center	Terre Haute	Indiana
United States	Arizona Oncology Associates D.B.A. Hematology Oncology	Tucson	Arizona
United States	Tyler Cancer Center	Tyler	Texas
United States	Northwest Cancer Specialists, Pc	Vancouver	Washington
United States	Texas Oncology Cancer Care And Research Center	Waco	Texas
United States	Deke Slayton Cancer Center	Webster	Texas
United States	Alliance Hematology Oncology, Pa	Westminster	Maryland
United States	Yakima Valley Memorial Hospital/North Star Lodge	Yakima	Washington

Sponsors (2)

Lead Sponsor	Collaborator
R-Pharm	US Oncology Research

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants With Death as Outcome, Treatment-related (TR) Deaths, SAEs, TR SAEs, Adverse Events (AEs) Leading to Discontinuation, AEs, TR AEs, GR 3-4 AEs, TR GR 3-4 AEs, Drug-related (DR) Peripheral Neuropathy, Neutropenia, Alopecia	An AE is any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical event that at any dose: results in death, persistent or significant disability/incapacity, drug dependency or abuse; is life-threatening, an important medical event, a congenital anomaly/birth defect; requires inpatient hospitalization; or prolongs existing hospitalization. Treatment related=possibly, probably, or certainly related to and of unknown relationship to study treatment. GR=Grade.	Assessed from the date of first dose until at least 30 days after the last dose of study drug. Median time on study therapy was 12 weeks (range: 4-60 weeks for 16 mg/m^2 arm; 3-87 weeks for 40 mg/m^2 arm).	Yes
Primary	Progression-Free Survival (PFS) at 6 Months (6-month PFS Rate): Proportion of Participants Progression Free at 6 Months	PFS at 6 months was defined as proportion of participants who neither progressed nor died before 6 months. Computed using Kaplan-Meier estimates.	From the date of randomization to 6-months on study	No
Secondary	Median Progression Free Survival	PFS is defined as time interval from the date of randomization to the date of (first) progression or date of death. Participants who progressed or died were counted as events. Participants lost to follow-up were censored as of the last date of contact. Participants who started a new treatment before they progressed were censored as of the date of start of the new treatment. Participants who had not progressed or died were censored at the date of last follow-up. PFS (months) = (End date - date of randomization + 1)/30.4375.	From the date of randomization to date of progression, death, or last tumor assessment (maximum participant PFS of 25.7 months)	No
Secondary	Overall Response Rate (ORR) Based on Response Criteria in Solid Tumors [RECIST]	ORR is defined as the proportion of responders (complete response [CR] + partial response [PR] in participants with measurable disease) in that arm among all randomized participants.; CR: Disappearance of all evidence of target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (LD) of all target lesions.; Measurable disease: Lesions that can be accurately measured in at least one dimension (LD to be recorded) as =20 mm with conventional techniques (computed tomography [CT], magnetic resonance imaging [MRI], X-ray) or as =10 mm with spiral CT scan.	Assessed at 12-week intervals until disease progression (to a maximum follow-up for tumor response of 26.3 months)	No
Secondary	Best Response as Assessed With RECIST	Determined based on the sequence of disease status with corresponding best response. PD=At least a 20% increase in the sum of LD of target lesions in reference to the smallest sum LD recorded or the appearance of 1 or more new lesions; SD=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD in reference to the smallest sum LD. NE=Participants who discontinued treatment secondary to toxicity or died (either before completion of 1 treatment cycle). Please refer outcome measure 3 for explanation of CR and PR. CR+PR+SD=overall disease control.	Assessed at 12-week intervals until disease progression (to a maximum follow-up for tumor response of 26.3 months)	No
Secondary	Overall Survival (OS)	Survival was measured as the date of randomization to the date of death. Participants who were alive at the time of the database lock or lost to follow-up were censored at the last known alive date. The distribution of overall survival was analyzed via the Kaplan Meier method in each arm.; Survival time (months) = (End date - date of randomization + 1)/30.4375	From the date of randomization to date of death (maximum participant OS of 26.3 months)	No
Secondary	Time to Response	Time to response is defined as the time from the start of treatment until the first (confirmed) CR or PR was recorded. Time to response was computed only for participants whose best response was PR or CR.; CR: Disappearance of all target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (LD) of all target lesions with reference to the baseline sum LD.	From the date of first dose to date of first PR or CR assessment ( maximum participant time to response of 8.3 months)	No
Secondary	Duration of Response	Duration of overall response was defined as the period from the time first PR or CR was recorded until the first date of documented PD or death. Duration of response was computed for participants whose best response was either PR or CR. Participants who neither relapsed nor died were censored on the date of their last tumor assessment. Kaplan-Meier method was used to estimate the duration of response. Refer to outcome measures 3 and 4 for CR, PR, and PD.	From the date of first PR or CR assessment to date of progression, death, or last tumor assessment (maximum participant duration of response of 17.4 months)	No
Secondary	Incidence of All Grades of Peripheral Neuropathy	All events of peripheral neuropathy were assessed and graded per National Cancer Institute (NCI) Common Terminology Criteria Adverse Events (CTCAE)Version 3. CTC Grade (GR) 1=Mild; GR2=Moderate; GR3=Severe or medically significant, not immediately life-threatening; and GR4=Life-threatening. All treatment-related and not related Neuropathy and Peripheral Neuropathy were included; serious adverse events (SAEs) were not included.	Assessed from the date of first study dose until at least 30 days after the last dose of study drug. Median time on study therapy was 12 weeks (range: 4-60 weeks for 16 mg/m^2 arm; 3-87 weeks for 40 mg/m^2 arm).	Yes

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