First Line Therapy for Patients With Metastatic Breast Cancer

• Sponsor: Celgene (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00456846
• Collaborator: (none)
• Enrollment: 123
• Locations: 14
• Arm: 1
• Actual Duration (Months): 63.9
• Patients Per Site: 8.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the toxicity and anti-tumor activity of nab-paclitaxel 100mg/m^2 administered weekly in a 4-week cycle as first line therapy to patients with metastatic breast cancer who received taxanes as part of their adjuvant therapy and patients who did not receive taxanes as part of their adjuvant therapy.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Breast Cancer	Drug: ABI-007	Phase 2

Detailed Description

This is an open-label, phase II study to determine the toxicity and antitumor activity of ABI-007 100 mg/m2 administered weekly for 3 weeks followed by a rest week (4-week cycle) as first line therapy to patients with metastatic breast cancer in the following 2 cohorts: Patients who have received a taxane as part of their adjuvant therapy, and patients who did not receive a taxane as part of their adjuvant therapy. Patients will be assessed for antitumor response every 8 weeks.

The last subject received study treatment 11DEC2012. The study was terminated on 31 May 2013 via a notification letter to all investigators on 14 May 2013.

Study Design

• Study Type: Interventional
• Actual Enrollment: 123 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Phase II Study of Weekly ABI-007 as First Line Therapy for Patients With Metastatic Breast Cancer
• Actual Study Start Date: Feb 1, 2008
• Actual Primary Completion Date: Dec 11, 2012
• Actual Study Completion Date: May 31, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ABI-007 100 mg/m^2 ABI-007 was administered by intravenous (IV) infusion over 30 minutes weekly for 3 weeks followed by 1 week rest. Therapy continued until disease progression or unacceptable toxicity.	Drug: ABI-007; 100 mg/m^2 ABI-007 weekly for 3 weeks followed by 1 week rest; Other Names: Nab-paclitaxel Abraxane

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Objective Confirmed Complete or Partial Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0 Based on Investigator and Independent Reviewers [Every 8 weeks from study start until disease progression; Up to 61 months]

   Overall response rate (ORR) is complete response (CR) + partial response (PR). Complete response (CR): The disappearance of all known disease and no new sites or disease related symptoms confirmed at least 4 weeks after initial documentation. All sites must be assessed, including non-measurable sites, such as effusions, or markers. Disappearance of all non-target lesions. The normalization of tumor marker level confirmed at least 4 weeks after initial documentation. Partial response (PR): At least a 30% decrease in the sum of the longest diameters of target lesions, taking as a reference the baseline sum of the longest diameters confirmed at least 4 weeks after initial documentation. PR is also recorded when all measurable disease has completely disappeared, but a non-measurable component (i.e., ascites) is still present but not progressing. As well as persistence of one or more non-target lesion(s) and/or the maintenance of tumor marker level above the normal limits

Secondary Outcome Measures

1. Percentage of Participants With Disease Control [Every 8 weeks from study start until disease progression; Up to 61 months]

   Disease control was defined as stable disease (SD) for ≥ 16 weeks or complete response (CR) or partial response (PR). Response was evaluated by the Investigator and by an independent reviewer using Response Evaluation Criteria in Solid Tumors (RECIST) guidelines version 1.0. See Outcome #1 for definitions of CR and PR. RECIST defines SD for target lesions as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, no occurrence of progression disease for non-target lesions, and no new lesions.

2. Progression-free Survival (PFS) [Study start until disease progression, death, or up to data cut off of 31 May 2013; up to 61 months]

   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 who did not have progression or did not die were censored at the last known time the participant was progression free. Participants who initiated other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated.

3. Duration of Response Based on Independent Reviewer Assessment [Initial response until disease progression; or until data cut off 31 May 2013; up to 61 months]

   Duration of response was defined as progression-free survival in responders, i.e. as the time between the start of a complete response (CR) or partial response (PR) and the start of progressive disease (PD) or patient death from any cause, whichever occurred first. Participants who did not have progression or had not died were censored at the last known time the participant was progression free. Participants who had initiated other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated. CR and PR were defined in outcome #1. 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. Response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST).

4. Duration of Response Based on Investigator Assessment [Initial response until disease progression; or until data cut off 31 May 2013; up to 61 months]

   Duration of response was defined as progression-free survival in responders, i.e. as the time between the start of a complete response (CR) or partial response (PR) and the start of progressive disease (PD) or patient death from any cause, whichever occurred first. Participants who did not have progression or had not died were censored at the last known time the participant was progression free. Participants who had initiated other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated. Complete response (CR) and partial response (PR) were defined in outcome #1. 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. Response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST).

5. Patient Survival [Study start until death, or until data cut-off 31 May 2013; up to 61 months]

   Participant survival was the time from the first dose of study drug to participant death from any cause. Participants who did not die were censored at the last known time the participant was alive.

6. Number of Participants Experiencing Dose Reductions, Interruptions, or Dose Delays of Study Drug [Day 1 of study drug to Day 940; data cut off 31 May 2013]

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

7. Number of Participants With Treatment-Emergent Adverse Events [Day 1 to Day 940]

   Count of study participants who had at least one treatment-emergent adverse event (TEAE) defined as any adverse event that began or worsened in grade after the start of study drug through 30 days after the last dose of study drug. The National Cancer Institute (NCI)'s Common Terminology Criteria for AEs (CTCAE) was used to grade AE severity: severity grade 3= severe and undesirable AE. Severity grade 4= life-threatening or disabling AE. Severity grade 5 = death.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Females with pathologically confirmed adenocarcinoma of the breast.

• No prior chemotherapy for metastatic breast cancer

• At least 12 months between completion of adjuvant chemotherapy and the diagnosis of metastatic disease

• Stage IV disease

• Measurable disease (must be equal or greater to 2.0 cm using conventional Computed Tomography (CT) or equal or greater to 1.0 cm using spiral CT except for pulmonary lesions that are well documented on conventional CT scan which must be equal or greater than 1.0 cm)

• At least 4 weeks since radiotherapy, with full recovery. The measurable disease must be completely outside the radiation portal or there must be radiologic or clinical exam 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

• Age equal or greater to 18

• Patients has the following blood counts at Baseline:

• Absolute Neutrophil Count (ANC) equal or greater to 1.5 x 10^9 cells/L

• Platelets equal or greater to 100 x 10^9 cells/L

• Hemoglobin (Hgb) equal or greater to 90 grams/L

• Patients has the following blood chemistry levels at Baseline:

• Aspartate aminotransferase (AST) Serum glutamic-oxaloacetic transaminase (SGOT), alanine aminotransferase (ALT) serum glutamic:pyruvic transaminase (SGPT)less than or equal to 2.5x upper limit of normal range (ULN);

• total bilirubin normal (unless bilirubin elevation is due to Gilbert's (Disease);

• alkaline phosphatase less than or equal 2.5x ULN (unless bone metastasis is present in the absence of liver metastasis);

• Creatinine less than or equal to 1.5mg/dL

• Current sensory neuropathy Grade 0 or 1 by Breast Cancer Index (BCI) Common Toxicity Criteria Adverse Events (CTCAE)

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

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

• Patient is able to supply unstained slides or 1 tumor block of her primary breast tumor or a biopsy of a current site of metastasis for Secreted protein acidic and rich in cysteine (SPARC) analysis

• Informed consent has been obtained

Exclusion Criteria:

• Concurrent immunotherapy or hormonal therapy (other than Herceptin) for breast cancer

• Parenchymal brain metastases, unless documented to be clinically and radiographically stable for at least 6 months after treatment

• Serious intercurrent medical or psychiatric illness, including serious active infection

• History of class II-IV congestive heart failure

• History of other malignancy within the last 5 years which could affect the diagnoses or assessment of breast cancer, with the exception of basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix

• Patients who have received an investigational drug within the previous 3 weeks

• Patient is currently enrolled in a different clinical study in which investigational procedures are performed or investigational therapies are administered. Also a patient may not enroll in such clinical trials while participating in this study.

• Pregnant or nursing women

• Patients with prior hypersensitivity to Taxol or Taxotere

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	BC Cancer Agency-Burnaby	Burnaby	British Columbia	Canada
2	Lions Gate Hospital	North Vancouver	British Columbia	Canada
3	B.C.C.A Vancouver Island Center	Victoria	British Columbia	Canada
4	Dr. H. Bliss Murphy Cancer Center	St. Johns	Newfoundland and Labrador	Canada
5	The Royal Victoria Hospital	Barrie	Ontario	Canada
6	London Regional Cancer Centre	London	Ontario	Canada
7	Mount Sinai Hospital	Toronto	Ontario	Canada
8	St. Michael's Hospital	Toronto	Ontario	Canada
9	Toronto Synnybrook Cancer Centre	Toronto	Ontario	Canada
10	Windsor Regional Hospital	Windsor	Ontario	Canada
11	Hospital de la Cite-de-la Sante-de-Laval	Laval	Quebec	Canada
12	Centre Hospitalier de l'Universite de Montreal-Hotel-Dieu	Montreal	Quebec	Canada
13	McGill University	Montreal	Quebec	Canada
14	CHA: Saint Sacrement Hospital	Quebec		Canada

Sponsors and Collaborators

• Celgene

Investigators

• Principal Investigator: Sasha Smiljanik, MD, Lions Gate Hospital
• Principal Investigator: Kara Laing, MD, Dr. H. Bliss Murphy Cancer Center
• Principal Investigator: Wendy Lam, MD, BC Cancer Agency-Burnaby
• Principal Investigator: Maureen Trudeau, MD, Toronto Sunnybrook Cancer Centre
• Principal Investigator: Vanessa Bernstein, MD, B.C.C.A. Vancouver Island Center
• Principal Investigator: Jawaid Younus, MD, London Regional Cancer Centre
• Principal Investigator: Lawrence Panasci, MD, McGill University
• Principal Investigator: Guy Cantin, MD, CHA: Saint Sacrement Hospital
• Principal Investigator: Nicolas Raymond, MD, Hospital de la Cite-de-la Sante-de-Laval
• Principal Investigator: Robert El-Maraghi, MD, The Royal Victoria Hospital
• Principal Investigator: Christine Brezden-Masley, MD, Unity Health Toronto
• Principal Investigator: Andre Robidoux, MD, Centre Hospitalier de l'Universite de Montreal-Hotel-Dieu
• Principal Investigator: Martin Blackstein, MD, MOUNT SINAI HOSPITAL
• Principal Investigator: Caroline Hamm, MD, Windsor Regional Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

• Brezden B, et al. An open-label, phase II study of weekly nab-paclitaxel as first-line therapy for patients (pts) with metastatic breast cancer (MBC): Safety update. Presented at 2010 ASCO Annual Meeting, June 4-8, 2010, Chicago, IL. Abstract No 1127 C.

• Responsible Party: Celgene
• ClinicalTrials.gov Identifier: NCT00456846
• Other Study ID Numbers: CA042
• First Posted: Apr 5, 2007
• Last Update Posted: Nov 22, 2019
• Last Verified: Nov 1, 2019

• Keywords provided by Celgene: Metastatic Breast Cancer, ABI-007, Abraxane
• Additional relevant MeSH terms: Breast Neoplasms; Paclitaxel; Albumin-Bound Paclitaxel

Study Results

Participant Flow

Arm/Group Title	Abraxane (Prior Taxane Therapy)	Abraxane (No Prior Taxane Therapy)
Arm/Group Description	Participants who had received a taxane as part of their adjuvant therapy received Abraxane (ABI-007) at 100 mg/m^2 given intravenously (IV) over 30 minutes weekly for 3 weeks followed by 1 week rest. Therapy continued until disease progression or unacceptable toxicity.	Participants who had not received a taxane as part of their adjuvant therapy received Abraxane (ABI-007) at 100 mg/m^2 given intravenously (IV) over 30 minutes weekly for 3 weeks followed by 1 week rest. Therapy continued until disease progression or unacceptable toxicity.
Period Title: Overall Study
STARTED	47	76
COMPLETED	31	48
NOT COMPLETED	16	28

Baseline Characteristics

Arm/Group Title	Abraxane (Prior Taxane Therapy)	Abraxane (No Prior Taxane Therapy)	Total
Arm/Group Description	Participants who had received a taxane as part of their adjuvant therapy received Abraxane (ABI-007) at 100 mg/m^2 given intravenously (IV) over 30 minutes weekly for 3 weeks followed by 1 week rest	Participants who had not received a taxane as part of their adjuvant therapy received Abraxane (ABI-007) at 100 mg/m^2 given intravenously (IV) over 30 minutes weekly for 3 weeks followed by 1 week rest	Total of all reporting groups
Overall Participants	47	76	123
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.3 (9.78)	58.3 (10.88)	57.2 (10.54)
Sex: Female, Male (Count of Participants)
Female	47 100%	76 100%	123 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (participants) [Number]
Asian	0 0%	5 6.6%	5 4.1%
Black, of African Heritage	2 4.3%	3 3.9%	5 4.1%
Native Hawaiian or Other Pacific Islander	1 2.1%	0 0%	1 0.8%
White, Non-Hispanic/Non Latino	41 87.2%	60 78.9%	101 82.1%
White, Hispanic or Latino	0 0%	5 6.6%	5 4.1%
Other-Unspecified	3 6.4%	3 3.9%	6 4.9%
Menopausal Status (participants) [Number]
Premenopausal	12 25.5%	12 15.8%	24 19.5%
Postmenopausal	35 74.5%	64 84.2%	99 80.5%
Stage at Primary Diagnosis (participants) [Number]
Stage I	4 8.5%	12 15.8%	16 13%
Stage IIa	7 14.9%	12 15.8%	19 15.4%
Stage IIb	14 29.8%	13 17.1%	27 22%
Stage IIIa	11 23.4%	8 10.5%	19 15.4%
Stage IIIb	6 12.8%	4 5.3%	10 8.1%
Stage IIIc	5 10.6%	5 6.6%	10 8.1%
Stage IV	0 0%	19 25%	19 15.4%
Unknown	0 0%	3 3.9%	3 2.4%
Eastern Cooperative Oncology Group (ECOG) Performance Status (participants) [Number]
0 (fully active)	21 44.7%	38 50%	59 48%
1 (restrictive but ambulatory)	22 46.8%	30 39.5%	52 42.3%
2 (ambulatory but unable to work)	4 8.5%	8 10.5%	12 9.8%
3 (limited self-care) + 4 (completely disabled)	0 0%	0 0%	0 0%
Physician Assessment of Peripheral Neuropathy] [2] (participants) [Number]
Grade 0	37 78.7%	69 90.8%	106 86.2%
Grade 1	10 21.3%	7 9.2%	17 13.8%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Objective Confirmed Complete or Partial Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0 Based on Investigator and Independent Reviewers
Description	Overall response rate (ORR) is complete response (CR) + partial response (PR). Complete response (CR): The disappearance of all known disease and no new sites or disease related symptoms confirmed at least 4 weeks after initial documentation. All sites must be assessed, including non-measurable sites, such as effusions, or markers. Disappearance of all non-target lesions. The normalization of tumor marker level confirmed at least 4 weeks after initial documentation. Partial response (PR): At least a 30% decrease in the sum of the longest diameters of target lesions, taking as a reference the baseline sum of the longest diameters confirmed at least 4 weeks after initial documentation. PR is also recorded when all measurable disease has completely disappeared, but a non-measurable component (i.e., ascites) is still present but not progressing. As well as persistence of one or more non-target lesion(s) and/or the maintenance of tumor marker level above the normal limits
Time Frame	Every 8 weeks from study start until disease progression; Up to 61 months

Outcome Measure Data

Analysis Population Description

Treated Population: The Treated population consisted of all enrolled participants who received at least one dose of study drug.

Arm/Group Title	Abraxane (Prior Taxane Therapy)	Abraxane (No Prior Taxane Therapy)
Arm/Group Description	Participants who had received a taxane as part of their adjuvant therapy received Abraxane (ABI-007) at 100 mg/m^2 given intravenously (IV) over 30 minutes weekly for 3 weeks followed by 1 week rest	Participants who had not received a taxane as part of their adjuvant therapy received Abraxane (ABI-007) at 100 mg/m^2 given intravenously (IV) over 30 minutes weekly for 3 weeks followed by 1 week rest
Measure Participants	47	76
Investigator Assessment	30 63.8%	28 36.8%
Independent Reviewer Assessment	32 68.1%	32 42.1%

2. Secondary Outcome

Title	Percentage of Participants With Disease Control
Description	Disease control was defined as stable disease (SD) for ≥ 16 weeks or complete response (CR) or partial response (PR). Response was evaluated by the Investigator and by an independent reviewer using Response Evaluation Criteria in Solid Tumors (RECIST) guidelines version 1.0. See Outcome #1 for definitions of CR and PR. RECIST defines SD for target lesions as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, no occurrence of progression disease for non-target lesions, and no new lesions.
Time Frame	Every 8 weeks from study start until disease progression; Up to 61 months

Outcome Measure Data

Analysis Population Description

Treated Population: The Treated population consisted of all enrolled participants who received at least one dose of study drug.

Arm/Group Title	Abraxane (Prior Taxane Therapy)	Abraxane (No Prior Taxane Therapy)
Arm/Group Description	Participants who had received a taxane as part of their adjuvant therapy received Abraxane (ABI-007) at 100 mg/m^2 given intravenously (IV) over 30 minutes weekly for 3 weeks followed by 1 week rest	Participants who had not received a taxane as part of their adjuvant therapy received Abraxane (ABI-007) at 100 mg/m^2 given intravenously (IV) over 30 minutes weekly for 3 weeks followed by 1 week rest
Measure Participants	47	76
Investigator Assessment	51 108.5%	57 75%
Independent Reviewer Assessment	55 117%	57 75%

3. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	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 who did not have progression or did not die were censored at the last known time the participant was progression free. Participants who initiated other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated.
Time Frame	Study start until disease progression, death, or up to data cut off of 31 May 2013; up to 61 months

Outcome Measure Data

Analysis Population Description

Treated Population: The Treated population consisted of all enrolled participants who received at least one dose of study drug.

Arm/Group Title	Abraxane (Prior Taxane Therapy)	Abraxane (No Prior Taxane Therapy)
Arm/Group Description	Participants who had received a taxane as part of their adjuvant therapy received Abraxane (ABI-007) at 100 mg/m^2 given intravenously (IV) over 30 minutes weekly for 3 weeks followed by 1 week rest	Participants who had not received a taxane as part of their adjuvant therapy received Abraxane (ABI-007) at 100 mg/m^2 given intravenously (IV) over 30 minutes weekly for 3 weeks followed by 1 week rest
Measure Participants	47	76
Investigator Assessment	6.0	6.7
Independent Reviewer Assessment	5.3	5.3

4. Secondary Outcome

Title	Duration of Response Based on Independent Reviewer Assessment
Description	Duration of response was defined as progression-free survival in responders, i.e. as the time between the start of a complete response (CR) or partial response (PR) and the start of progressive disease (PD) or patient death from any cause, whichever occurred first. Participants who did not have progression or had not died were censored at the last known time the participant was progression free. Participants who had initiated other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated. CR and PR were defined in outcome #1. 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. Response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST).
Time Frame	Initial response until disease progression; or until data cut off 31 May 2013; up to 61 months

Outcome Measure Data

Analysis Population Description

Treated Population: The Treated population with a confirmed complete response or partial response.

Arm/Group Title	Abraxane (Prior Taxane Therapy)	Abraxane (No Prior Taxane Therapy)
Arm/Group Description	Participants who had received a taxane as part of their adjuvant therapy received Abraxane (ABI-007) at 100 mg/m^2 given intravenously (IV) over 30 minutes weekly for 3 weeks followed by 1 week rest	Participants who had not received a taxane as part of their adjuvant therapy received Abraxane (ABI-007) at 100 mg/m^2 given intravenously (IV) over 30 minutes weekly for 3 weeks followed by 1 week rest
Measure Participants	15	24
Median (95% Confidence Interval) [months]	10.9	9.2

5. Secondary Outcome

Title	Duration of Response Based on Investigator Assessment
Description	Duration of response was defined as progression-free survival in responders, i.e. as the time between the start of a complete response (CR) or partial response (PR) and the start of progressive disease (PD) or patient death from any cause, whichever occurred first. Participants who did not have progression or had not died were censored at the last known time the participant was progression free. Participants who had initiated other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated. Complete response (CR) and partial response (PR) were defined in outcome #1. 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. Response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST).
Time Frame	Initial response until disease progression; or until data cut off 31 May 2013; up to 61 months

Outcome Measure Data

Analysis Population Description

Treated Population: The Treated population consisted of all enrolled participants that received at least one dose of study drug.

Arm/Group Title	Abraxane (Prior Taxane Therapy)	Abraxane (No Prior Taxane Therapy)
Arm/Group Description	Participants who had received a taxane as part of their adjuvant therapy received Abraxane (ABI-007) at 100 mg/m^2 given intravenously (IV) over 30 minutes weekly for 3 weeks followed by 1 week rest	Participants who had not received a taxane as part of their adjuvant therapy received Abraxane (ABI-007) at 100 mg/m^2 given intravenously (IV) over 30 minutes weekly for 3 weeks followed by 1 week rest
Measure Participants	14	21
Median (95% Confidence Interval) [months]	10.5	10.8

6. Secondary Outcome

Title	Patient Survival
Description	Participant survival was the time from the first dose of study drug to participant death from any cause. Participants who did not die were censored at the last known time the participant was alive.
Time Frame	Study start until death, or until data cut-off 31 May 2013; up to 61 months

Outcome Measure Data

Analysis Population Description

Treated Population: The Treated population consisted of all enrolled participants that received at least one dose of study drug.

Arm/Group Title	Abraxane (Prior Taxane Therapy)	Abraxane (No Prior Taxane Therapy)
Arm/Group Description	Participants who had received a taxane as part of their adjuvant therapy received Abraxane (ABI-007) at 100 mg/m^2 given intravenously (IV) over 30 minutes weekly for 3 weeks followed by 1 week rest	Participants who had not received a taxane as part of their adjuvant therapy received Abraxane (ABI-007) at 100 mg/m^2 given intravenously (IV) over 30 minutes weekly for 3 weeks followed by 1 week rest
Measure Participants	47	76
Median (95% Confidence Interval) [months]	20.9	20.0

7. Secondary Outcome

Title	Number of Participants Experiencing Dose Reductions, Interruptions, or Dose Delays of Study Drug
Description	The number of participants with dose reductions, dose interruptions and dose delays that occurred during the treatment period. Dose reductions, interruptions and delays are typically caused by clinically significant laboratory abnormalities and /or treatment emergent adverse events/toxicities.
Time Frame	Day 1 of study drug to Day 940; data cut off 31 May 2013

Outcome Measure Data

Analysis Population Description

Treated Population: The Treated population consisted of all enrolled participants who received at least one dose of study drug.

Arm/Group Title	Abraxane (Prior Taxane Therapy)	Abraxane (No Prior Taxane Therapy)
Arm/Group Description	Participants who had received a taxane as part of their adjuvant therapy received Abraxane (ABI-007) at 100 mg/m^2 given intravenously (IV) over 30 minutes weekly for 3 weeks followed by 1 week rest	Participants who had not received a taxane as part of their adjuvant therapy received Abraxane (ABI-007) at 100 mg/m^2 given intravenously (IV) over 30 minutes weekly for 3 weeks followed by 1 week rest
Measure Participants	47	76
Patients with at Least One Dose Reduction	11 23.4%	19 25%
Patients with at Least One Dose Interruption	3 6.4%	2 2.6%
Patients with at Least One Dose Delay/Not Given	20 42.6%	39 51.3%

8. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events
Description	Count of study participants who had at least one treatment-emergent adverse event (TEAE) defined as any adverse event that began or worsened in grade after the start of study drug through 30 days after the last dose of study drug. The National Cancer Institute (NCI)'s Common Terminology Criteria for AEs (CTCAE) was used to grade AE severity: severity grade 3= severe and undesirable AE. Severity grade 4= life-threatening or disabling AE. Severity grade 5 = death.
Time Frame	Day 1 to Day 940

Outcome Measure Data

Analysis Population Description

Treated Population: The Treated population consisted of all enrolled participants who received at least one dose of study drug.

Arm/Group Title	Abraxane (Prior Taxane Therapy)	Abraxane (No Prior Taxane Therapy)
Arm/Group Description	Participants who had received a taxane as part of their adjuvant therapy received Abraxane (ABI-007) at 100 mg/m^2 given intravenously (IV) over 30 minutes weekly for 3 weeks followed by 1 week rest	Participants who had not received a taxane as part of their adjuvant therapy received Abraxane (ABI-007) at 100 mg/m^2 given intravenously (IV) over 30 minutes weekly for 3 weeks followed by 1 week rest
Measure Participants	47	76
≥1 Adverse Event (AE)	46 97.9%	75 98.7%
≥1 Treatment related Adverse Event	41 87.2%	74 97.4%
≥ 1 Serious Adverse Event	5 10.6%	14 18.4%
Treatment related Serious Adverse Event	2 4.3%	7 9.2%
≥1 One Grade 3/4 Adverse Event	25 53.2%	36 47.4%
≥1 One Grade 3 or Higher Adverse Event	25 53.2%	36 47.4%
≥1 AE leading to treatment discontinuation	2 4.3%	16 21.1%
≥1 AE leading to death	0 0%	2 2.6%
≥1 AE leading to dose reduction of study drug	11 23.4%	18 23.7%
≥1 AE leading to dose interruption of study drug	2 4.3%	0 0%
≥1 AE leading to dose delay of study drug	15 31.9%	29 38.2%

Adverse Events

Time Frame	Any Adverse Event (AE) that started after initial study drug administration through the end of the study or 30 days after the last treatment, whichever was later, were followed until the AE had resolved or stabilized. Upt to 61 months.
Arm/Group Title	Abraxane (Prior Taxane Therapy)		Abraxane (No Prior Taxane Therapy)
Arm/Group Description	Participants who had received a taxane as part of their adjuvant therapy received Abraxane (ABI-007) at 100 mg/m^2 given intravenously (IV) over 30 minutes weekly for 3 weeks followed by 1 week rest		Participants who had not received a taxane as part of their adjuvant therapy received Abraxane (ABI-007) at 100 mg/m^2 given intravenously (IV) over 30 minutes weekly for 3 weeks followed by 1 week rest
All Cause Mortality
	Abraxane (Prior Taxane Therapy)		Abraxane (No Prior Taxane Therapy)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Abraxane (Prior Taxane Therapy)		Abraxane (No Prior Taxane Therapy)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/47 (10.6%)		14/76 (18.4%)
Cardiac disorders
Left ventricular dysfunction	0/47 (0%)		1/76 (1.3%)
Pericardial effusion	1/47 (2.1%)		0/76 (0%)
Gastrointestinal disorders
Diarrhoea	1/47 (2.1%)		0/76 (0%)
Lower gastrointestinal haemorrhage	1/47 (2.1%)		0/76 (0%)
General disorders
Chest pain	0/47 (0%)		1/76 (1.3%)
General physical health deterioration	0/47 (0%)		1/76 (1.3%)
Mucosal inflammation	0/47 (0%)		1/76 (1.3%)
Hepatobiliary disorders
Hepatic cirrhosis	0/47 (0%)		1/76 (1.3%)
Infections and infestations
Pneumonia	0/47 (0%)		3/76 (3.9%)
Bacteraemia	1/47 (2.1%)		0/76 (0%)
Bronchopneumonia	0/47 (0%)		1/76 (1.3%)
Cellulitis	1/47 (2.1%)		0/76 (0%)
Histoplasmosis	0/47 (0%)		1/76 (1.3%)
Lung infection	0/47 (0%)		1/76 (1.3%)
Injury, poisoning and procedural complications
Ankle fracture	0/47 (0%)		1/76 (1.3%)
Cervical vertebral fracture	0/47 (0%)		1/76 (1.3%)
Hip fracture	0/47 (0%)		1/76 (1.3%)
Post procedural haemorrhage	0/47 (0%)		1/76 (1.3%)
Musculoskeletal and connective tissue disorders
Chondrocalcinosis pyrophosphate	0/47 (0%)		1/76 (1.3%)
Musculoskeletal chest pain	1/47 (2.1%)		0/76 (0%)
Pathological fracture	0/47 (0%)		1/76 (1.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain	1/47 (2.1%)		0/76 (0%)
Metastases to bone	0/47 (0%)		1/76 (1.3%)
Nervous system disorders
Somnolence	0/47 (0%)		1/76 (1.3%)
Psychiatric disorders
Confusional state	1/47 (2.1%)		0/76 (0%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion	0/47 (0%)		2/76 (2.6%)
Pulmonary embolism	0/47 (0%)		2/76 (2.6%)
Dyspnoea	0/47 (0%)		1/76 (1.3%)
Hypoxia	0/47 (0%)		1/76 (1.3%)
Pneumothorax	1/47 (2.1%)		0/76 (0%)
Skin and subcutaneous tissue disorders
Stevens-Johnson syndrome	0/47 (0%)		1/76 (1.3%)
Other (Not Including Serious) Adverse Events
	Abraxane (Prior Taxane Therapy)		Abraxane (No Prior Taxane Therapy)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	46/47 (97.9%)		75/76 (98.7%)
Blood and lymphatic system disorders
Anaemia	3/47 (6.4%)		4/76 (5.3%)
Neutropenia	7/47 (14.9%)		13/76 (17.1%)
Thrombocytopenia	3/47 (6.4%)		2/76 (2.6%)
Eye disorders
Dry eye	1/47 (2.1%)		5/76 (6.6%)
Lacrimation increased	5/47 (10.6%)		14/76 (18.4%)
Vision blurred	5/47 (10.6%)		5/76 (6.6%)
Gastrointestinal disorders
Abdominal pain	3/47 (6.4%)		12/76 (15.8%)
Abdominal pain upper	1/47 (2.1%)		4/76 (5.3%)
Constipation	15/47 (31.9%)		15/76 (19.7%)
Diarrhoea	15/47 (31.9%)		37/76 (48.7%)
Dry mouth	3/47 (6.4%)		3/76 (3.9%)
Dyspepsia	11/47 (23.4%)		9/76 (11.8%)
Dysphagia	4/47 (8.5%)		2/76 (2.6%)
Gastrooesophageal reflux disease	3/47 (6.4%)		2/76 (2.6%)
Haemorrhoids	1/47 (2.1%)		4/76 (5.3%)
Nausea	24/47 (51.1%)		47/76 (61.8%)
Stomatitis	6/47 (12.8%)		18/76 (23.7%)
Vomiting	13/47 (27.7%)		22/76 (28.9%)
General disorders
Asthenia	5/47 (10.6%)		6/76 (7.9%)
Chills	6/47 (12.8%)		5/76 (6.6%)
Fatigue	33/47 (70.2%)		55/76 (72.4%)
Influenza like illness	1/47 (2.1%)		5/76 (6.6%)
Mucosal inflammation	1/47 (2.1%)		4/76 (5.3%)
Non-cardiac chest pain	3/47 (6.4%)		4/76 (5.3%)
Oedema	2/47 (4.3%)		4/76 (5.3%)
Oedema peripheral	13/47 (27.7%)		22/76 (28.9%)
Pain	4/47 (8.5%)		3/76 (3.9%)
Performance status decreased	2/47 (4.3%)		6/76 (7.9%)
Pyrexia	8/47 (17%)		17/76 (22.4%)
Infections and infestations
Cellulitis	3/47 (6.4%)		0/76 (0%)
Influenza	2/47 (4.3%)		4/76 (5.3%)
Nasopharyngitis	4/47 (8.5%)		6/76 (7.9%)
Sinusitis	4/47 (8.5%)		4/76 (5.3%)
Upper respiratory tract infection	6/47 (12.8%)		6/76 (7.9%)
Urinary tract infection	6/47 (12.8%)		8/76 (10.5%)
Injury, poisoning and procedural complications
Fall	3/47 (6.4%)		1/76 (1.3%)
Investigations
Aspartate aminotransferase increased	0/47 (0%)		5/76 (6.6%)
Haemoglobin decreased	4/47 (8.5%)		9/76 (11.8%)
Neutrophil count decreased	0/47 (0%)		4/76 (5.3%)
Weight decreased	6/47 (12.8%)		6/76 (7.9%)
Weight increased	6/47 (12.8%)		7/76 (9.2%)
Metabolism and nutrition disorders
Decreased appetite	16/47 (34%)		30/76 (39.5%)
Hypokalaemia	2/47 (4.3%)		5/76 (6.6%)
Musculoskeletal and connective tissue disorders
Arthralgia	7/47 (14.9%)		14/76 (18.4%)
Back pain	12/47 (25.5%)		13/76 (17.1%)
Bone pain	9/47 (19.1%)		6/76 (7.9%)
Flank pain	3/47 (6.4%)		4/76 (5.3%)
Muscular weakness	0/47 (0%)		6/76 (7.9%)
Musculoskeletal chest pain	6/47 (12.8%)		6/76 (7.9%)
Musculoskeletal pain	5/47 (10.6%)		4/76 (5.3%)
Myalgia	15/47 (31.9%)		13/76 (17.1%)
Pain in extremity	14/47 (29.8%)		15/76 (19.7%)
Nervous system disorders
Dizziness	10/47 (21.3%)		17/76 (22.4%)
Dysgeusia	10/47 (21.3%)		19/76 (25%)
Headache	17/47 (36.2%)		20/76 (26.3%)
Hypoaesthesia	5/47 (10.6%)		4/76 (5.3%)
Peripheral motor neuropathy	3/47 (6.4%)		1/76 (1.3%)
Peripheral sensory neuropathy	22/47 (46.8%)		44/76 (57.9%)
Somnolence	4/47 (8.5%)		1/76 (1.3%)
Depression	5/47 (10.6%)		5/76 (6.6%)
Insomnia	6/47 (12.8%)		15/76 (19.7%)
Mood altered	1/47 (2.1%)		4/76 (5.3%)
Psychiatric disorders
Anxiety	3/47 (6.4%)		10/76 (13.2%)
Renal and urinary disorders
Urinary incontinence	0/47 (0%)		4/76 (5.3%)
Reproductive system and breast disorders
Breast pain	0/47 (0%)		4/76 (5.3%)
Respiratory, thoracic and mediastinal disorders
Cough	12/47 (25.5%)		18/76 (23.7%)
Dysphonia	2/47 (4.3%)		4/76 (5.3%)
Dyspnoea	10/47 (21.3%)		20/76 (26.3%)
Dyspnoea exertional	3/47 (6.4%)		2/76 (2.6%)
Epistaxis	10/47 (21.3%)		21/76 (27.6%)
Nasal dryness	2/47 (4.3%)		7/76 (9.2%)
Oropharyngeal pain	4/47 (8.5%)		7/76 (9.2%)
Productive cough	3/47 (6.4%)		1/76 (1.3%)
Rhinorrhoea	7/47 (14.9%)		7/76 (9.2%)
Skin and subcutaneous tissue disorders
Alopecia	29/47 (61.7%)		61/76 (80.3%)
Dry skin	5/47 (10.6%)		6/76 (7.9%)
Erythema	2/47 (4.3%)		6/76 (7.9%)
Nail disorder	12/47 (25.5%)		20/76 (26.3%)
Pruritus	4/47 (8.5%)		4/76 (5.3%)
Rash	3/47 (6.4%)		14/76 (18.4%)
Vascular disorders
Hot flush	4/47 (8.5%)		11/76 (14.5%)
Hypertension	1/47 (2.1%)		4/76 (5.3%)
Lymphoedema	3/47 (6.4%)		2/76 (2.6%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Institution may publish the results of its findings if a multicenter publication is not forthcoming within 18 months after study completion. Institution shall provide Celgene with a copy of the papers prior to their submission; Celgene shall complete its review within 60 days after receipt. Upon Celgene's request, proposed publication or presentation will be delayed up to 60 additional days to enable Celgene to secure adequate intellectual property protection of patentable material.