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Phase II Study of Ixabepilone in Metastatic Breast Cancer and Its Effects on the Ultrastructure of Neurons

Phase 2
Completed
Conditions
Metastatic Breast Cancer
Interventions
Registration Number
NCT00627978
Lead Sponsor
Weill Medical College of Cornell University
Brief Summary

Primary Objectives

* Assess ultrastructure changes in dermal myelinated nerves of patients who receive ixabepilone chemotherapy

* Detailed characterization of peripheral neuropathy in patients who receive ixabepilone

Secondary Objectives

* Clinical benefit rate

* Time to progression ( TTP)

* Toxicity

* Exploratory studies:

* Relation of MDR 1 and TRKA polymorphisms to evolution of ultrastructural neurologic changes observed in neurons.

* Relation of NGF, IL8, and IL10 to the development of clinical symptoms and ultrastructural changes in neurons.

Detailed Description

Eligible patient population:

* Stage 4 breast cancer

* Resolution from toxicity of prior therapy to ≤ CTC grade 1 ( except alopecia)

* No limit on prior number of therapies to treat cancer

* Adequate organ function

* Life expectancy greater than 3 months

Treatment: ixabepilone 40 mg/m2 Q3w over 3 hours

Evaluation on Study:

I. Efficacy evaluation:

* Baseline CT chest, abdomen and pelvis and bone scan within 4 weeks of starting therapy

* Evaluation of disease every 2 cycles of chemotherapy

* Ongoing toxicity evaluation using NCI CTC 3.

II. Neurological evaluation:

* Detailed neurologic exam using Neuropathy Assessment Instrument (represents a standard neurological exam)

* Serum NGF, IL 8,10, prior to starting therapy and prior to each cycle of ixabepilone

* DNA for assessment of TRK A and MDR1 polymorphisms

* Punch biopsy of skin prior to starting therapy and after every 2 cycles. Laboratory evaluation of peripheral nerve biopsies will be conducted at Rockefeller University under the direction of Dr. Carlson in Dr. Strickland's Lab.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
15
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
IxabepiloneixabepiloneParticipants are treated with Ixabepilone.
Primary Outcome Measures
NameTimeMethod
Axons With Abnormal MorphologyBaseline and Over 7 cycles of treatment, approximately 21 weeks

Digital photographs for morphometry were captured at a magnification of 8000-16,000x and the photos were uploaded onto an imaging platform of transmission electron microscope (iTEM) (Olympus, Mu¨nster, Germany). The figures were enlarged by 50%, and an individual linear array was used to measure the axonal diameter (cross-sectional area) and the number of unmyelinated axons per Remak Schwann cell was enumerated according to the established methodology.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Weill Medical College of Cornell University

🇺🇸

New York, New York, United States

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