Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Breast Neoplasms

Neoplasm Metastasis

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Pharmaceutical Solutions

Capecitabine

Taxane

Epothilones

Antimetabolites

Tubulin Modulators

Antimitotic Agents

Ixabepilone - Intravenous Solution, IV 40mg/m², Day 1 every 21 days, Until progression/unacceptable toxicity

Capecitabine (Active Comparator) - Tablet, Oral, 2000 mg/m², Bid Days 1-14 every 21 days, Until progression/unacceptable toxicity

Ixabepilone + Capecitabine

Tablet, Oral, 2500 mg/m², Bid Days 1-14 every 21 days, Until progression/unacceptable toxicity

Bristol-Myers Squibb

The purpose of this clinical research study is to learn if BMS-247550 added to the approved therapy of capecitabine is better than capecitabine alone in shrinking or slowing the growth of the cancer in women with metastatic breast cancer who are resistant to taxane and received anthracycline chemotherapy. The safety of this treatment will also be studied.

Novel Epothilone Plus Capecitabine Versus Capecitabine Alone in Patients With Advanced Breast Cancer

A Phase III Trial of Novel Epothilone BMS-247550 Plus Capecitabine Versus Capecitabine Alone in Patients With Advanced Breast Cancer Previously Treated With or Resistant to an Anthracycline and Who Are Taxane Resistant

PFS defined as the time in months from randomization to date of progression. Patients who died without a reported prior progression were considered to have progressed on date of death; those who didn't progress or die were censored on date of last tumor assessment. Median PFS time with 95% CI estimated using the Kaplan Meier product limit method.

Participants with best response of "Complete" or "Partial" according to Response Evaluation Criteria in Solid Tumors (RECIST) a 4-item scale wherein complete response=disappearance of all target lesions and partial response=30% decrease in the sum of the longest diameter of target lesions

Computed for all patients with a best response of "Partial" or "Complete" per RECIST (a 4-item scale as described in previous outcome measure), calculated from the time when these criteria were first met until the first date of documented progression or death.

Time to response was summarized using descriptive statistics and was defined as the time from first dose of study treatment until measurement criteria were first met for Partial Response or Complete Response.

OS was defined as the time from randomization to death. Participants who did not die at the time of the analysis were censored at the latest follow-up date. Median OS with 95% CI was estimated using the Kaplan Meier product limit method.

Laboratory values, adverse events, and other symptoms were graded using the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTC) Version 3.0

Quality of life, as measured by the FBSI, an 8-item, participant-reported instrument to measure symptoms. Each item has 5 possible responses ranging from 0 (not at all) to 4 (very much). The scoring was conducted according to the Functional Assessment of Chronic Illness Therapy manual, Version 4; higher scores reflect fewer symptoms.

R-Pharm

Study Director

Ixabepilone 40 mg/m2 administered as a 3-hour intravenous (IV) infusion on Day 1 of each 21-day cycle, plus oral capecitabine 1000 mg/m2 twice a day (BID) x 14 days

Total

<65 years

>= 65 years

<50 years

>= 50 years

Unknown

Age, Customized

Age, Continuous

Sex: Female, Male

American Indian or Alaska Native

Asian

Black or African American

White

Other

Race/Ethnicity, Customized

Ascites

Bone

Breast

Chest Wall

Effusion

Lymph Node

Peritoneum

Pleura

Skin/Soft Tissue

Visceral, Liver

Visceral, Lung

Visceral, Other

Disease Sites

Liver ± Lung ± Skin/Soft Tissue ± Bone

Lung ± Skin/Soft Tissue ± Bone

Skin/Soft Tissue ± Bone

Disease Sites at Baseline

Not reported

Karnofsky Performance Scale Index measures a patient's functional impairment: 100-80=Able to carry on normal activity and work, no special care; 70-50=Unable to work; able to live at home and care for most personal needs with assistance; 40-0=Unable to care for self; institutional or hospital care needed. Score reported in multiples of 10.

Karnofsky Performance Status

Premenopausal

Perimenopausal

Postmenopausal

Menopausal Status

1 disease site

2 disease sites

3 disease sites

4 disease sites

≥5 disease sites

Number of Disease Sites

Subjects with at least 1 lesion

Subjects with no lesions

Presence of All Lesions

Missing

Visceral Disease in Liver and/or Lung

Bristol-Myers Squibb Study Director

Study required 615 events to achieve 90% power to detect a hazard ratio of 0.77 using a 2-sided α = 0.05 log-rank test. The analysis was a comparison between the 2 treatment arms using a 2-sided α=0.0483 log-rank test (adjusted for an interim analysis using the O'Brien Fleming spending function) to reject the null hypothesis of equality of progression free survival. The analysis was conducted when 639 events (310 in combination:329 in capecitabine) were observed from the 752 randomized patients.

PFS was analyzed on all randomized patients on an intention to treat basis.

Progression-free Survival (PFS) Per Independent Radiology Review Committee (IRRC)

The study had 95 percent power to detect a significant difference in ORR if the true response rate was 32 percent in the combination arm and 20 percent in the capecitabine arm.

The analysis of ORR was conducted on all randomized patients on an intent to treat basis.

Overall Response Rate (ORR) Per IRRC

Results for duration of response apply to only those subjects with a response (defined as complete or partial response).

Duration of Response Per IRRC

Results for time to response apply to only those subjects with a response (defined as complete or partial response)

Time to Response Per IRRC

Study required 631 deaths to achieve 80% power to detect a Hazard ratio of 0.8 using a 2-sided α = 0.05 log rank test. The analysis was a comparison between the 2 treatment arms using a 2-sided α=0.05 log-rank test to reject the null hypothesis of equality of survival. The analysis was conducted when 639 deaths (318 in combination:321 in capecitabine) were observed from the 752 randomized patients.

Overall survival was analyzed on all randomized patients on an intent to treat basis.

Overall Survival (OS)

Deaths on-study or within 30 days of last dose

Treatment-related Serious Adverse Events (SAEs)

Treatment-related Adverse Events (AEs)

Treatment-related AEs leading to Discontinuation

Ixabepilone in combination with capecitabine (combination group): Ixabepilone 40 mg/m2 administered as a 3-hour intravenous (IV) infusion on Day 1 of each cycle only, plus oral capecitabine 1000 mg/m2 twice a day (BID) (2000 mg/m2 daily dose) x 14 days, followed by 1 week of rest.

All treated participants; all participants who received at least 1 dose of study therapy.Participants with baseline hepatic impairment (combination arm, n = 29; capecitabine arm, n = 35), defined as Grade ≥2 AST, ALT or Grade ≥1 total bilirubin, were contraindicated due to disproportionate number of toxic deaths.

Treatment-related Safety Summary

There was a statistically significant difference between groups in change from baseline FBSI score favoring capecitabine. A mean change from baseline of 2.5 was considered a clinically meaningful difference (minimally important difference or MID). On-treatment mean changes in the FBSI did not reach the MID in either group.

Week 3 (n=282; n=273)

Week 6 (n=227; n=214)

Week 9 (n=194; n=184)

Week 12 (n=173; n=158)

Week 15 (n=148; n=145)

Week 18 (n=122; n=121)

Week 21 (n=116; n=101)

Week 24 (n=95; n=82)

Analysis was conducted on all randomized participants on an intent to treat basis.(Note: while table only reports data up to 24 wks, which represents most results, statistical analysis includes ALL assessments through study and follow-up; a few participants were assessed after more than 100 weeks.)

Symptom Assessment Score Changes From Baseline for Functional Assessment of Cancer Therapy-Breast Symptom Index (FBSI)

Overall Study

Ixabepilone lypholized powder/Diluent for solution for injection/Tablets, IV/Oral, 40 mg/m2 + Capecitabine 2000 mg/m2, Ixabepilone on Day 1 and Capecitabine twice daily Days 1-14 of 21 day cycle

Tablet, Oral, 2500 mg/m2, Capecitabine twice daily Days 1-14 of 21 day cycle

The purpose of this clinical research study is to learn if BMS-247550 added to the approved therapy of capecitabine (Xeloda) provides measurable clinical benefits over capecitabine alone in women with metastatic breast cancer. Patients should have previously received an anthracycline and a taxane. The safety of this treatment will also be studied.

Epothilone (Ixabepilone) Plus Capecitabine Versus Capecitabine Alone in Patients With Advanced Breast Cancer

A Phase III Study of Novel Epothilone (Ixabepilone) Plus Capecitabine Versus Capecitabine Alone in Patients With Advanced Breast Cancer Previously Treated With an Anthracycline and a Taxane

Overall survival was defined as the time in months from randomization until the date of death. For those patients who had not died, survival duration was censored at the last date the patient was known to be alive. Median OS with 95% CI estimated using the Kaplan-Meier Product Limit Method.

PFS was defined for each patient as the time in months from randomization to the date of progression. Patients who died without a reported prior progression were considered to have progressed on their date of death. Patients who did not progress or die were censored on the date of their last tumor assessment.

RR=number of patients in that group whose best response is "partial"(30% decrease in the sum of the longest diameter of target lesions) or "complete" (disappearance of all target lesions), according to the 4-item Response Evaluation Criteria in Solid Tumors (RECIST), divided by the total number of response-evaluable participants

Measured from the time RECIST criteria (described in previous outcome measure) were first met for "complete" or "partial" response until first date of documented disease progression or death. Patients who neither relapsed nor died were censored on the date of last tumor assessment. Median w/ 95% CI estimated using Kaplan Meier Product Limit Method.

Time to response was defined as the time from the first dose of study therapy until measurement criteria were first met for "partial" or "complete" (whichever status was recorded first) per RECIST criteria (a 4-item scale described in the previous outcome measure).

Capecitabine alone: Capecitabine 1250 mg/m2 BID (2500 mg/m2 daily dose) x 14 days, followed by 1 week of rest.

≥65 years

≥50 years

Unknown or Not Reported

not reported

Karnofsky Performance Scale Index measures a patient's functional impairment: 100-80=able to carry on normal activity and work, no special care; 70-50=unable to work; able to live at home and care for most personal needs with assistance; 40=unable to care for self; requires institutional or hospital care. Score reported in multiples of 10.

Karnofsky performance Status

Not Reported

Brain

Chest Wall Mass

Cutaneous

Intestine

Mediastinum

Subcutaneous

Organ Sites

Presence with at least 1 lesion

The analysis was conducted when 903 progressions or deaths (446 in combination:457 in capecitabine) were observed in 960 participants.

All randomized patients with measurable disease as stratified at the time of randomization; n=480 and n=480 for the 2 treatment groups, respectively. Analysis was conducted once 903 progressions or deaths were observed in 960 participants.

Progression-Free Survival (PFS)

Response-evaluable participants (all treated participants with the correct diagnosis of adenocarcinoma originating in the breast who had measurable disease as determined at baseline).

Response Rate (RR)

Response-evaluable participants (all treated patients with the correct diagnosis of adenocarcinoma originating in the breast who had measurable disease as determined at baseline)

Duration of Response

Time to Response

Deaths within 30 days of last dose

Treatment-related serious adverse events

Treatment-related Grade 3-4 adverse events

Treatment-related AEs leading to discontinuation

All patients who received at least 1 dose of ixabepilone and/or capecitabine. Participants with baseline hepatic impairment (combination arm, n = 50; capecitabine arm, n = 37), defined as Grade ≥2 AST, ALT or Grade ≥1 total bilirubin, were contraindicated due to disproportionate number of toxic deaths observed in study CA163-046.

Treatment-Related Safety Summary

Week 3 (n=440; n=429)

Week 6 (n=379; n=353)

Week 9 (n=330; n=283)

Week 12 (n=283; n=250)

Week 15 (n=255; n=240)

Week 18 (n=205; n=202)

Week 21 (n=166; n=185)

Week 24 (n=149; n=141)

Analysis was conducted on all randomized participants on an intent to treat basis. (Note: while table only reports data up to 24 wks, which represents most results, statistical analysis includes ALL assessments through study and follow-up; a few participants were assessed after more than 100 weeks.)

This primary analysis was a comparison between the 2 treatment arms using a 2-sided, α=0.05 level log-rank test (to reject the null hypothesis of equality of survival). The analysis was conducted when 880 deaths (430 in combination:450 in capecitabine) were observed from the 1221 randomized participants.

This prespecified secondary analysis was a Cox model adjusted for age, Karnofsky performance status, number of organ sites, estrogen receptor status, hepatic impairment, time from diagnosis, liver/lung metastases.

Analysis was conducted on all randomized patients on an intent to treat basis. This study required at least 846 events (deaths) to ensure the 2-sided, α = 0.05 level, log-rank test to have 90% power to show a statistically significant difference in OS between treatment groups when the hazard ratio (HR) is 0.8.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Novel Epothilone Plus Capecitabine Versus Capecitabine Alone in Patients With Advanced Breast Cancer	NCT00080301	Breast Cancer Metastases	Ixabepilone + C... Capecitabine	18 Years -	R-Pharm
Novel Epothilone Plus Capecitabine Versus Capecitabine Alone in Patients With Advanced Breast Cancer	NCT00080301	Breast Cancer Metastases	Ixabepilone + C... Capecitabine	18 Years -	R-Pharm
Epothilone (Ixabepilone) Plus Capecitabine Versus Capecitabine Alone in Patients With Advanced Breast Cancer	NCT00082433	Cancer Breast Cancer	Ixabepilone + C... Capecitabine	18 Years -	R-Pharm
Epothilone (Ixabepilone) Plus Capecitabine Versus Capecitabine Alone in Patients With Advanced Breast Cancer	NCT00082433	Cancer Breast Cancer	Ixabepilone + C... Capecitabine	18 Years -	R-Pharm
Novel Epothilone Plus Capecitabine Versus Capecitabine Alone in Patients With Advanced Breast Cancer	NCT00080301	Breast Cancer Metastases	Ixabepilone + C... Capecitabine	18 Years -	R-Pharm

Spots Global Cancer Trial Database for ixabepilone + capecitabine