Amifostine in Treating Peripheral Neuropathy Caused by Paclitaxel in Patients With Solid Tumors

Phase II Trial Of Subcutaneous Amifostine For Reversal Of Persistent Paclitaxel-Induced Peripheral Neuropathy

RATIONALE: Amifostine may be effective in reducing pain, numbness, tingling, and other symptoms of peripheral neuropathy.

PURPOSE: This phase II trial is studying how well amifostine works in reducing pain, numbness, tingling, and other symptoms of peripheral neuropathy in patients who have received paclitaxel for solid tumors.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Ovarian Cancer; Lung Cancer; Prostate Cancer; Unspecified Adult Solid Tumor, Protocol Specific; Neurotoxicity
• Intervention / Treatment: Drug: Amifostine

Detailed Description

OBJECTIVES:

Primary

• Determine the percentage of patients with solid tumors who have persistent paclitaxel-induced peripheral neuropathy who benefit, defined as a decrease of at least 20% on their FUNCTIONAL ASSESSMENT OF CANCER THERAPY/ GYNECOLOGIC ONCOLOGY GROUP NEUROTOXICITY (FACT/GOG-Ntx) FACT-GOG-NTX score, from treatment with subcutaneous amifostine.
• Determine whether there is sufficient evidence of reversal activity of this drug in these patients to justify a phase III study.

Secondary

• Compare the acute toxic effects of this drug administered subcutaneously in these patients vs IV administrations of this drug historically and/or during the GOG-0192 study.
• Determine the capability of the Weinstein Enhanced Sensory Test to provide objective, quantitative evidence for improvement in patients who have subjective improvement as self-reported on the FACT-GOG-NTX scale.
• Determine whether any benefit in patients treated with this drug is transient or lasts at least 8 weeks.

OUTLINE: This is an open-label, multicenter study.

Patients receive amifostine subcutaneously three times weekly for 4 weeks in the absence of symptom progression or unacceptable toxicity. Patients achieving a complete or partial response receive an additional 4 weeks of therapy.

Neuropathy symptoms are assessed using the FACT-GOG-NTX questionnaire administered at baseline, weekly during therapy, and at 12 weeks and the Weinstein Enhanced Sensory Test administered at baseline and at 4, 8, and 12 weeks.

Patients are followed at 12 weeks.

PROJECTED ACCRUAL: A total of 20-40 patients will be accrued for this study within 10-20 months.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Decatur, Illinois, United States, 62526
      • CCOP - Central Illinois
    • Urbana, Illinois, United States, 61801
      • CCOP - Carle Cancer Center
  • Kansas
    • Wichita, Kansas, United States, 67214-3882
      • CCOP - Wichita
  • Louisiana
    • Alexandria, Louisiana, United States, 71301
      • Christus St. Frances Cabrini Center for Cancer Care
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • CCOP - Grand Rapids
    • Kalamazoo, Michigan, United States, 49007-3731
      • CCOP - Kalamazoo
  • Missouri
    • Kansas City, Missouri, United States, 64131
      • CCOP - Kansas City
    • Springfield, Missouri, United States, 65807
      • Cancer Research for the Ozarks
  • Ohio
    • Columbus, Ohio, United States, 43215
      • CCOP - Columbus
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • CCOP - Upstate Carolina
  • Texas
    • Houston, Texas, United States, 77030-4009
      • University of Texas M.D. Anderson CCOP Research Base
    • Temple, Texas, United States, 76508
      • CCOP - Scott and White Hospital
  • Washington
    • Tacoma, Washington, United States, 98405-0986
      • CCOP - Northwest
  • Wisconsin
    • Marshfield, Wisconsin, United States, 54449
      • CCOP - Marshfield Clinic Research Foundation
    • Racine, Wisconsin, United States, 53405
      • All Saints Cancer Center at Wheaton Franciscan Healthcare

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Diagnosis of a solid tumor, including, but not limited to the following:

  • Ovarian cancer
  • Lung cancer
  • Prostate cancer
  • Breast cancer
• Previously treated with paclitaxel

• Peripheral neuropathy (e.g., numbness, tingling, and/or pain in distal extremities) believed to be caused by paclitaxel only or the combination of paclitaxel and carboplatin

  • At least 18 out of 44 on the FACT-GOG-NTX scale
  • Persistent neuropathy for at least 2, but no more than 12 months after chemotherapy
  • Not improving
• No other possible cause of neuropathy (e.g., alcoholism, diabetes, or peripheral vascular disease)

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Age

• 18 and over

Sex

• Not specified

Menopausal status

• Not specified

Performance status

• Karnofsky 50-100%

Life expectancy

• More than 2 months

Hematopoietic

• Not specified

Hepatic

• Bilirubin ≤ 2.0 mg/dL

Renal

• Creatinine ≤ 2.0 mg/dL
• Calcium ≥ lower limit of normal

Cardiovascular

• See Disease Characteristics
• No prior cerebrovascular accident

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other significant comorbid medical condition that would preclude study participation
• No known sensitivity to aminothiol compounds

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics
• No prior cisplatin
• No chemotherapy during and for at least 3 months after study participation

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• No concurrent monoamine oxidase inhibitors

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Amifostine; 500 mg subcutaneous three times a week on Monday, Wednesday and Friday for 4 weeks.	Drug: Amifostine; 500 mg three times a week.; Other Names: amifostine trihydrate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurotoxicity secondary to cancer therapy as measured by FACT-GOG-NTX scale	11-item FACT/GOG-NTX questionnaire completed weekly following chemotherapy treatment.	12 weeks

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Arthur Forman, MD, M.D. Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start: May 1, 2004
• Primary Completion (Actual): May 1, 2007
• Study Completion (Actual): May 1, 2007

Study Registration Dates

• First Submitted: March 8, 2004
• First Submitted That Met QC Criteria: March 8, 2004
• First Posted (Estimate): March 9, 2004

Study Record Updates

• Last Update Posted (Estimate): October 17, 2012
• Last Update Submitted That Met QC Criteria: October 16, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: stage IV breast cancer; stage IIIA breast cancer; recurrent breast cancer; stage IIIB breast cancer; recurrent non-small cell lung cancer; extensive stage small cell lung cancer; recurrent small cell lung cancer; stage III prostate cancer; stage IV prostate cancer; recurrent prostate cancer; stage IIIA non-small cell lung cancer; stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer; unspecified adult solid tumor, protocol specific; stage I non-small cell lung cancer; stage II non-small cell lung cancer; stage III ovarian epithelial cancer; stage IV ovarian epithelial cancer; recurrent ovarian epithelial cancer; stage II breast cancer; stage IIIC breast cancer; neurotoxicity; stage I breast cancer; limited stage small cell lung cancer; stage I prostate cancer; stage IIB prostate cancer; stage IIA prostate cancer; stage I ovarian epithelial cancer; stage II ovarian epithelial cancer
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Nervous System Diseases; Skin Diseases; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Breast Diseases; Prostatic Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neuromuscular Diseases; Poisoning; Breast Neoplasms; Prostatic Neoplasms; Lung Neoplasms; Peripheral Nervous System Diseases; Neurotoxicity Syndromes; Physiological Effects of Drugs; Protective Agents; Radiation-Protective Agents; Amifostine
• Other Study ID Numbers: CDR0000330006; MDA-CCC-0223; MDA-CCC-0203; MDA-2003-0789