First Line Therapy for Patients With Metastatic Breast Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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An Open-Label, Phase II Study of Weekly ABI-007 as First Line Therapy for Patients With Metastatic Breast Cancer

Conditions
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Metastatic Breast Cancer

Intervention / Treatment
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* Drug: ABI-007


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABI-007<br>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<br>* 100 mg/m^2 ABI-007 weekly for 3 weeks followed by 1 week rest<br>* Other names: Abraxane;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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 | Every 8 weeks from study start until disease progression; Up to 61 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Disease Control | 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. | Every 8 weeks from study start until disease progression; Up to 61 months | 
| 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 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. | Study start until disease progression, death, or up to data cut off of 31 May 2013; up to 61 months | 
| Duration of Response Based on Independent Reviewer Assessment | 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). | Initial response until disease progression; or until data cut off 31 May 2013; up to 61 months | 
| Duration of Response Based on Investigator Assessment | 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). | Initial response until disease progression; or until data cut off 31 May 2013; up to 61 months | 
| Patient Survival | 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. | Study start until death, or until data cut-off 31 May 2013; up to 61 months | 
| Number of Participants Experiencing Dose Reductions, Interruptions, or Dose Delays of Study Drug | 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. | Day 1 of study drug to Day 940; data cut off 31 May 2013 | 
| Number of Participants With Treatment-Emergent Adverse Events | 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. | Day 1 to Day 940 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic Breast Cancer, ABI-007, Abraxane