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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00039780
Recruitment Status : Completed
First Posted : June 13, 2002
Last Update Posted : September 25, 2017
Information provided by (Responsible Party):
BioNumerik Pharmaceuticals, Inc.

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

Condition or disease Intervention/treatment Phase
Breast Neoplasms Breast Diseases Metastases, Neoplasm Drug: BNP7787 Drug: Placebo Phase 3

Detailed Description:

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 764 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: BNP7787 vs. Placebo for Prevention of Paclitaxel Neurotoxicity: A Double-Blind Multicenter Randomized Phase 3 Trial in Patients With Metastatic Breast Cancer
Study Start Date : September 2001
Actual Primary Completion Date : October 2006
Actual Study Completion Date : September 2014

Resource links provided by the National Library of Medicine

Drug Information available for: Paclitaxel

Arm Intervention/treatment
Active Comparator: 1
Tavocept (BNP7787)
Drug: BNP7787
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.
Other Name: BNP7787 also known as Tavocept

Placebo Comparator: 2
0.9% Sodium Chloride Soln.
Drug: Placebo
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.

Primary Outcome Measures :
  1. 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 [ Time Frame: baseline to disease progression or discontinuation from study ]

Secondary Outcome Measures :
  1. Incidence of Dose Modifications, Treatment Delays and Treatment Discontinuations due to Neurotoxicity [ Time Frame: baseline to end of treatment ]
  2. Time-to-onset of clinically important neurotoxicity [ Time Frame: randomization to date of first occurrence of clinically important neurotoxicity ]
  3. Incidence of Neurosensory and Neuromotor Functional Impairment [ Time Frame: baseline through end of treatment ]
  4. Progression Free Survival [ Time Frame: Randomization to disease progression or death due to any cause ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No


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


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.

Responsible Party: BioNumerik Pharmaceuticals, Inc. Identifier: NCT00039780     History of Changes
Other Study ID Numbers: DMS30203R
First Posted: June 13, 2002    Key Record Dates
Last Update Posted: September 25, 2017
Last Verified: September 2017

Keywords provided by BioNumerik Pharmaceuticals, Inc.:

Additional relevant MeSH terms:
Breast Neoplasms
Neurotoxicity Syndromes
Breast Diseases
Neoplasm Metastasis
Neoplasms by Site
Skin Diseases
Nervous System Diseases
Chemically-Induced Disorders
Neoplastic Processes
Pathologic Processes
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs