A Phase II Open Label Study of E7389 (Halichondrin B Analog) in Patients With Advanced/Metastatic Breast Cancer Previously Treated With Chemotherapy Including An Anthracycline and A Taxane
Overview
- Phase
- Phase 2
- Intervention
- E7389
- Conditions
- Breast Neoplasms
- Sponsor
- Eisai Inc.
- Enrollment
- 104
- Primary Endpoint
- Overall Response Rate Based on Response Evaluation Criteria in Solid Tumors (RECIST)
- Status
- Completed
- Last Updated
- 13 years ago
Overview
Brief Summary
The purpose of this study is to determine if E7389 is a safe and effective treatment for advanced/metastatic breast cancer.
Detailed Description
The primary objective is to determine the response rate (RR) to E7389 monotherapy administered as an IV bolus of 1.4 mg/m\^2 on Days 1, 8, and 15 of a 28-Day cycle and on Days 1 and 8 of a 21-day cycle in patients with advanced/metastatic breast cancer treated with chemotherapy including an anthracycline and a taxane, with previously documented progression during or within six months following the last dose of prior chemotherapy. The secondary objectives are to evaluate: * The safety and tolerability of E7389 monotherapy in this patient population; * The antitumor activity of E7389 as determined by duration of response, time to progression, and overall survival; * Quality of life measured by the Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaire/tumor-related symptom improvement or worsening measured by pain intensity on a visual analog scale (VAS), analgesics consumption, weight changes and performance status (PS); * Tumor pharmacogenetics and their possible relationship to response (assessment of beta-tubulin isotype mRNA on biopsy sample) in patients who have signed a separate consent form
Investigators
Eligibility Criteria
Inclusion Criteria
- •Female patients with histologically or cytologically confirmed carcinoma of the breast
- •Patients with advanced/metastatic disease that is not amenable to curative therapy (either surgery or radiation therapy)
- •Patients must have measurable disease by the RECIST criteria, defined as at least one lesion that can be accurately measured in at least one diameter (at least 10 mm in longest diameter (LD) by spiral computer tomography (CT) scan, or at least 20 mm by standard techniques; If the only measurable lesion is a lymph node, it must measure at least 20 mm in LD. If a single lesion is identified as the target lesion, a cytological or histological confirmation of breast carcinoma is required.
- •Patients must have had prior treatment with an anthracycline and a taxane (either sequential or in combination) and may have had prior treatment with other agents as well.
- •Patients must have progressed within six months of the last dose of chemotherapy, or experienced disease progression while receiving chemotherapy for advanced/metastatic disease.
- •Resolution of all chemotherapy or radiation-related toxicities to less than grade 1 severity
- •Age ≥ 18 years
- •Eastern Cooperative Oncology Group (ECOG) Performance Status (APPENDIX 4) of 0 or 1
- •Life expectancy of ≥ 3 months
- •Adequate renal function as evidenced by serum creatinine ≤ 1.5 mg/dL or calculated creatinine clearance ≥ 50 mL/minute (min) per the Cockcroft and Gault formula
Exclusion Criteria
- •Patients who have received chemotherapy, radiation, hormonal therapy, or Herceptin within 2 weeks of E7389 treatment start
- •Radiation therapy encompassing \> 10% of marrow
- •Failure to recover from any chemotherapy related or other therapy related toxicity at study entry that is deemed to be clinically significant by the study investigator
- •Prior treatment with Mitomycin C or nitrosoureas
- •Prior high dose chemotherapy with hematopoietic stem cell rescue in the past two years
- •Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen
- •Active symptomatic brain metastasis; Patients with central Nervous System (CNS) metastasis are considered eligible if they have completed local therapy and discontinued from corticosteroids for at least two weeks before starting treatment with E7389
- •Patients with meningeal carcinomatosis
- •Patients who require therapeutic anti-coagulant therapy with Warfarin or related compounds; Mini dose warfarin for catheter related thrombosis prophylaxis is permitted
- •Women who are pregnant or breast-feeding; Women of childbearing potential with either a positive pregnancy test at Screening or no pregnancy test. Women of childbearing potential unless (1) surgically sterile or (2) using adequate measures of contraception in the opinion of the Investigator. Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.
Arms & Interventions
E7389
Intervention: E7389
Outcomes
Primary Outcomes
Overall Response Rate Based on Response Evaluation Criteria in Solid Tumors (RECIST)
Time Frame: Confirmed 4 to 8 weeks after first observed
Defined as the percentage of subjects with CR or PR from the start of treatment until disease progression or recurrence. Lesions measured by computed tomography (CT) scan and magnetic resonance imaging (MRI). Objective response rate: complete response (CR-disappearance of all lesions)+ partial response (PR-30% decrease in lesion diameter), Progressive Disease (PD-20% increase in lesion diameter), stable disease (SD-neither shrinkage nor increase of lesions).
Secondary Outcomes
- Duration of Response(From CR or partial response PR (whichever recorded first) to date of recurrent or progressive disease)
- Progression Free Survival(From start of study drug administration to progressive disease or death)
- Overall Survival(From start of study drug administration to death)
- Change From Baseline to Study Termination in Quality of Life Measures Using Functional Assessment of Cancer Therapy-Breast (FACT-B) Scores(At Screening, Day 1 of each cycle, and 30 days after last dose of study drug)