Evaluation of BNP7787 for the Prevention of Neurotoxicity in Metastatic Breast Cancer Patients Receiving Weekly Paclitaxel

Study Overview
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Brief Summary
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The purpose of this study is to determine whether BNP7787 is effective in preventing or reducing neurotoxicity (nerve damage) caused by paclitaxel (Taxol®).

Detailed Description
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Chemotherapy induced toxicities are common and serious problems for many patients who receive treatment for cancer. Chemotherapy induced toxicities can adversely impact the quality of life and the ability of patients to continue treatment for their cancer. One such toxicity associated with the use of paclitaxel (Taxol®) is peripheral neurotoxicity. Paclitaxel is an active drug in the treatment of metastatic breast cancer as first-line treatment and in patients with recurrent or refractory disease, including patients who have failed to respond to previous anthracycline therapy. Recent studies with paclitaxel using a weekly schedule of administration have demonstrated higher tumor response rates and disease free survival accompanied by a shift in the frequency of certain toxicities, increased dose intensity and a potential means to improve the treatment schedule of paclitaxel for improved patient benefit. Paclitaxel induced neurotoxicity remains an important problem that limits the ability to improve the schedule of administration of this drug. To date, there is no effective or FDA approved therapy to prevent the development of or reduce the frequency or severity of paclitaxel-induced neurotoxicity. BNP7787 is an investigational new drug that is undergoing development for chemoprotection of platinum and taxane associated common clinical toxicities, particularly the prevention of chemotherapy-induced neurotoxicity. In this Phase 3 clinical trial the safety and effectiveness of BNP7787 in preventing or mitigating the frequency, severity, worsening of grade, time to onset, duration and discontinuation of therapy due to paclitaxel-induced neurotoxicity will be assessed in patients with metastatic breast cancer.

Official Title
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BNP7787 vs. Placebo for Prevention of Paclitaxel Neurotoxicity: A Double-Blind Multicenter Randomized Phase 3 Trial in Patients With Metastatic Breast Cancer

Conditions
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Breast Neoplasms, Breast Diseases, Metastases, Neoplasm

Intervention / Treatment
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* Drug: BNP7787
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA Histologically or cytologically documented metastatic breast cancer Measurable disease Performance Status; ECOG 0-2 More than 2 weeks since prior radiation therapy 14 days or more since prior therapy and recovered from all side effects For patients who progress while receiving hormonal therapy alone, the patient may be enrolled on study as soon as they have recovered from all side effects of the hormonal therapy Clinical laboratory values must meet the following: Granulocytes greater than or equal to 1,500/mm(3) Platelets greater than or equal to 100,000/mm(3) Hemoglobin greater than or equal to 9 g/dL SGOT less than 2.0 x ULN Bilirubin less than or equal to 1.5 mg/dL Creatinine less than or equal to 1.6 mg/dL Calcium less than the ULN EXCLUSION CRITERIA Current CNS metastases or history of CNS metastases History of diabetes (Type I or Type II) Previous or concurrent malignancy except: inactive non-melanoma skin cancer in situ carcinoma of the cervix or other cancer if the patient has been disease-free for more than 5 years Pregnant or lactating women History of recent myocardial infarction, stroke, or uncontrolled CHF, epilepsy, or hypertension Patients currently receiving Neurontin® (gabapentin), glutamine supplements, Elavil® (amitriptyline), Dilantin®, Tegretol®, tricyclic antidepressants or other similar medications during the study period Alternative medications including megadose vitamins, herbal preparations, tonics, extracts, etc. are not allowed during the study period.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Tavocept (BNP7787) | Drug: BNP7787<br>* The treatment regimen administered in this study is a single IV doxe of paclitaxel (80 mg/m2) +/- Herceptin given over 1 hour and either BNP7787 (18.4 g/m2) or placebo given over 45 minutes each week. One treatment cycle = 8 weeks.<br>* Other names: BNP7787 also known as Tavocept;|
| Placebo Comparator: 2<br>0.9% Sodium Chloride Soln. | Drug: Placebo<br>* The treatment regimen administered in this study is a single IV doxe of paclitaxel (80 mg/m2) +/- Herceptin given over 1 hour and either BNP7787 (18.4 g/m2) or placebo given over 45 minutes each week. One treatment cycle = 8 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1)Incidence of PNQ Grade D or Grade E neurosensory symptoms (Item 1 of the PNQ) with duration of at least 4 weks; 2) Objective tumor response rate |  | baseline to disease progression or discontinuation from study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Dose Modifications, Treatment Delays and Treatment Discontinuations due to Neurotoxicity |  | baseline to end of treatment | 
| Time-to-onset of clinically important neurotoxicity |  | randomization to date of first occurrence of clinically important neurotoxicity | 
| Incidence of Neurosensory and Neuromotor Functional Impairment |  | baseline through end of treatment | 
| Progression Free Survival |  | Randomization to disease progression or death due to any cause | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast, Cancer, Metastatic, Paclitaxel, Peripheral, Taxol, Neuropathy, Neurotoxicity, Paresthesias, Weekly, BNP7787, 7787, Tavocept, Prevention