Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Breast Neoplasms

Triple Negative Breast Neoplasms

Recurrence

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Paclitaxel

Carboplatin

Hormones

Albumin-Bound Paclitaxel

Estrogens

Progesterone

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Treatment Arm A: nab-Paclitaxel 125 mg/m\^2 by intravenous (IV) administration over 30 minutes, followed by gemcitabine 1000 mg/m\^2 on Days 1 and 8 of each 21-day cycle by IV administration over 30 minutes

Treatment Arm B: nab-Paclitaxel 125 mg/m\^2 on Days 1 and 8 by IV administration followed by carboplatin at an Area Under the Curve (AUC) of 2 on Days 1 and 8 of each 21-day cycle by IV administration

Treatment Arm C: Gemcitabine 1000 mg/m\^2 on Days 1 and 8 by IV administration followed by carboplatin AUC 2 on Days 1 and 8 of each 21-day cycle by IV administration

nab-Paclitaxel 125 mg/m\^2 by IV administration over 30 minutes on Days 1 and 8 of each 21-day treatment cycle.

nab-Paclitaxel

Carboplatin at an AUC of 2 on Days 1 and 8 of each 21-day cycle by IV administration

Gemcitabine 1000 mg/m\^2 on Days 1 and 8 of each 21-day treatment cycle.

Ileana Elias, M.D.

The purpose of this study is to compare the safety and efficacy of nab-paclitaxel in combination with either gemcitabine or carboplatin to the combination of gemcitabine and carboplatin as first line treatment in female subjects with triple negative metastatic breast cancer (TNMBC) or metastatic triple negative breast cancer.

ABI-007-MBC- 001 is a Phase 2/3, multicenter, open-label, randomized, study that will compare the safety and efficacy of weekly nab-paclitaxel in combination with gemcitabine or carboplatin to the combination of gemcitabine and carboplatin as first line therapy in female subjects with Estrogen Receptor (ER), Progesterone Receptor (PgR), and human epidermal growth factor receptor 2 (HER2) negative (triple negative) metastatic breast cancer (TNMBC) or metastatic triple negative breast cancer. In the phase 2 portion of the study, the combinations of nab-paclitaxel plus gemcitabine and nab-paclitaxel plus carboplatin will be evaluated, and a comparator arm of gemcitabine combined with carboplatin will be used. In the phase 3 portion of the study, the selected nab-paclitaxel combination treatment will be compared to gemcitabine combined with carboplatin to evaluate progression free survival, safety and tolerability, overall survival, disease control rate and duration of response in women with metastatic triple negative breast cancer.

Due to changes in the treatment landscape since the initiation of this trial, the decision was made not to proceed to the Phase 3 portion of the study.

Evaluate Risk/Benefit of Nab Paclitaxel in Combination With Gemcitabine and Carboplatin Compared to Gemcitabine and Carboplatin in Triple Negative Metastatic Breast Cancer (or Metastatic Triple Negative Breast Cancer)

A Phase 2/3, Multi-Center, Open-Label, Randomized Study of Weekly Nab®-Paclitaxel in Combination With Gemcitabine or Carboplatin, Compared to Gemcitabine/Carboplatin, as First Line Treatment in Subjects With ER, PgR, and HER2 Negative (Triple Negative) Metastatic Breast Cancer

PFS was defined as the time from the date of randomization to the date of disease progression or death from any cause on or prior to the data cutoff date for the statistical analysis, whichever occurred earlier. Tumor responses were assessed every 6 weeks using, Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and defined as: Complete response (CR) is the disappearance of all target lesions; Partial response (PR) occurs when at least a 30% decrease in the sum of diameters of target lesions from baseline; Stable disease is neither sufficient shrinkage to qualify for a PR nor sufficient increase of lesions to qualify for Progressive disease (PD); Progressive Disease- is at least a 20% increase in the sum of diameters of target lesions from nadir.

Percentage of participants with an Objective Complete or Partial Overall Response according to RECIST 1.1 and defined as: Complete response-disappearance of all target lesions; partial response at least a 30% decrease in the sum of diameters of target lesions from baseline; stable disease-neither sufficient shrinkage to qualify for PR nor sufficient increase of lesions to qualify for Progressive disease (PD)• Progressive Disease- At least a 20% increase in the sum of diameters of target lesions from nadir.

The percentage of participants who initiated Cycle 6 receiving doublet combination therapy regardless of the need for dose modifications.

Overall survival was defined as the time from the date of randomization to the date of death (from any cause).

Treatment-emergent adverse events (TEAEs) were defined as any AEs that began or worsened with the onset date on or after the date of the first dose of IP through 28 days after the last dose. A serious AE (SAE) = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was graded based on the participant's symptoms according to the Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0); AEs were evaluated for severity as follows: Grade 1 = Mild - transient or mild discomfort; no medical intervention required; Grade 2 = Moderate - mild to moderate limitation in activity; Grade 3 = Severe; Grade 4 = Life threatening; Grade 5 = Death.

The number of participants with dose modifications occurring during the treatment period. Dose reductions and interruptions are typically caused by clinically significant laboratory abnormalities and /or treatment emergent adverse events/toxicities.

Treatment-emergent adverse events (TEAEs) were defined as any AEs that begin or worsen with an onset date on or after the date of the first dose of IP through 28 days after the last dose.

Celgene

Maximum treatment duration of study drug exposure was 108.3 weeks for Arm A, 83 weeks for Arm B and 110.1 weeks for Arm C

Participants received nab-Paclitaxel 125 mg/m\^2 on Days 1 and 8 by intravenous (IV) administration followed by gemcitabine 1000 mg/m\^2 on Days 1 and 8 by IV administration in each 21-day treatment cycle.

Arm A: Nab-Paclitaxel + Gemcitabine

Participants received nab-Paclitaxel 125 mg/m\^2 on Days 1 and 8 by IV administration followed by Carboplatin AUC 2 on Days 1 and 8 in each 21-day treatment cycle.

Arm B: Nab-Paclitaxel + Carboplatin

Participants received Gemcitabine 1000 mg/m\^2 on Days 1 and 8 by IV administration, followed by carboplatin AUC 2 on Days 1 and 8 by IV administration in each 21-day treatment cycle.

Arm C: Gemcitabine + Carboplatin

Participants received nab-Paclitaxel 125 mg/m\^2 on Days 1 and 8 by intravenous (IV) administration followed by gemcitabine 1000 mg/m\^2 on Days 1 and 8 by IV administration in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment.

Arm A: Nab-Paclitaxel Plus (+) Gemcitabine

Participants received nab-Paclitaxel 125 mg/m\^2 on Days 1 and 8 by IV administration followed by carboplatin area under the curve 2 (AUC 2) on Days 1 and 8 in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment.

Participants received gemcitabine 1000 mg/m\^2 on Days 1 and 8 by IV administration, followed by carboplatin AUC 2 on Days 1 and 8 by IV administration in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment.

Total

Age, Continuous

Sex: Female, Male

Black or African American

White

Unknown or Not Reported

Race

0 = Fully Active

1 = Restrictive but ambulatory

2 = Ambulatory but unable to work

Missing

ECOG performance status is used by doctors and researchers to assess how a subject's disease is progressing, assess how the disease affects the daily living activities of the subject and determine appropriate treatment and prognosis. 0 = Fully Active (Most Favorable Activity); 1 = Restricted activity but ambulatory; 2 = Ambulatory but unable to carry out work activities; 3 = Limited Self-Care; 4 = Completely Disabled, No self-care (Least Favorable Activity)

Eastern Cooperative Oncology Group (ECOG) Performance Status

≤ 1 year

> 1 year

Disease Free Interval is defined as period of being absent of disease less than or equal to one year or free of disease greater than one year.

Disease Free Interval by Clinical Interpretation

Time from Diagnosis to First Documented Disease/Relapse

Time from First Documented Metastatic Disease/Relapse to Study Randomization

Time from Primary Diagnosis to Randomization

Lymph Nodes(s)

Lung/Thoracic

Bone

Liver

Right/Left Breast

Skin/Soft Tissue

Other

Abdomen/Peritoneal

Current Sites of Metastasis

Stage 0

Stage IA

Stage IB

Stage IIA

Stage IIB

Stage IIIA

Stage IIIB

Stage IIIC

Stage IV

Invasive breast cancer stages:

* Stage 0-Stage 0 = noninvasive ductal carcinoma in situ
* Stage Ia-cancer cells are breaking through to or invading normal surrounding breast tissue.
* Stage IIa-breast tumor about 2cm and involvement of ancillary lymph nodes.
* Stage IIb-a larger tumor than earlier phases.
* Stage IIIa-axillary lymph nodes clumping together.
* Stage IIIb-spread further to the skin, breast bone or chest wall.
* Stage IIIc-expanded involvement of lymph nodes.
* Stage IV-cancer that has spread beyond the breast and nearby lymph nodes to other organs of the body.

Stage of Primary Diagnosis

Triple-Negative Breast Cancer defined as estrogen receptor (ER) negative, progesterone receptor (PgR) negative, and human epidermal growth factor receptor 2 (HER2) negative.

Triple-Negative Breast Cancer (TNBC) at Primary Diagnosis

Triple-Negative at Latest Diagnosis

Intent-to-treat (ITT) population includes all randomized participants regardless of whether they received any IP or had any efficacy assessments collected.

Due to changes in the treatment landscape since the trial initiation, including the initiation of trials with immunotherapy drugs, successful enrollment of the Phase 3 part was considered unlikely and was not conducted; no safety signals were raised.

Anne McClain, Senior Manager Clinical Trial Disclosure

For stratified analysis, the stratified log-rank test and stratified Cox proportional hazards model were used, where the stratification factor is the disease free interval (\<= 1 year; \> 1 year).

Participants received nab-Paclitaxel 125 mg/m\^2 on Days 1 and 8 by intravenous (IV) administration followed by gemcitabine 1000 mg/m\^2 on Days 1 and 8 by IV administration of each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment

ITT includes all randomized participants regardless of whether they received any IP or had any efficacy assessments collected. Those who did not have disease progression or had not died as of the data cutoff date were censored at the time of the last radiologic assessment prior to the data cutoff date.

Kaplan-Meier Estimates of Progression-Free Survival (PFS) Based on Investigator Assessment.

Percentage of Participants With an Objective Complete or Partial Overall Response by Investigator Assessment.

Percentage of Participants Who Initiated Cycle 6 Receiving Doublet Combination Therapy

Hazard ratios and associated two-sided 95% confidence intervals were estimated using stratified Cox proportional hazard model. The stratification factor is the disease free interval (≤ 1 year; \> 1 year).

The ITT population includes all randomized participants regardless of whether the participant received any Investigational Product (IP) or had any efficacy assessments collected.

Kaplan-Meier Estimates of Overall Survival

Any TEAE

Any Grade 3 or Higher TEAE

Treatment-related TEAE

Treatment-related, Grade 3 or Higher TEAE

Serious TEAE

Treatment-related Serious TEAE

TEAE Leading to Discontinuation (D/C) of IP

Treatment Related (TR) TEAE Leading to D/C of IP

TEAE Leading to Dose Reduction (DR) of IP

Treatment related TEAE Leading to DR of IP

TEAE Leading to Dose Interruption (DI) of IP

TR TEAE Leading to DI of IP

TEAE leading to D/C of nab-Paclitaxel

TR TEAE leading to D/C of nab-Paclitaxel

TEAE leading to DR of nab-Paclitaxel

TR TEAE leading to DR of nab-Paclitaxel

TEAE leading to DI of nab-Paclitaxel

TR TEAE leading to DI of nab-Paclitaxel

TEAE leading to D/C of Gemcitabine

TR TEAE leading to D/C of Gemcitabine

TEAE leading to DR of Gemcitabine

TR TEAE leading to DR of Gemcitabine

TEAE leading to DI of Gemcitabine

TR TEAE leading to DI of Gemcitabine

TEAE leading to D/C of Carboplatin

TR TEAE leading to D/C of Carboplatin

TEAE leading to DR of Carboplatin

TR TEAE leading to DR of Carboplatin

TEAE leading to DI of Carboplatin

TR TEAE leading to DI of Carboplatin

TEAE Leading to Death

Treatment Related TEAE leading to death

The safety population includes all randomized participants who received at least 1 dose of IP.

Number of Participants With Treatment Emergent Adverse Events (TEAEs)

≥ one DR for both IPs

≥ one DI for both IPs

≥ one dose missed for both IPs

The Safety/Treated population includes all randomized participants who received at least 1 dose of IP.

Spots Global Cancer Trial Database for progesterone negative receptor breast cancer