Baclofen-Amitriptyline Hydrochloride-Ketamine Gel in Treating Peripheral Neuropathy Caused by Chemotherapy in Patients With Cancer

Pain Clinical Trial

Official title:

The Use of Topical Baclofen, Amitriptyline HCI, and Ketamine (BAK) in a PLO Gel vs. Placebo for the Treatment of Chemotherapy Induced Peripheral Neuropathy: A Phase III Randomized Double-Blind Placebo Controlled Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00516503
• Other study ID #: NCCTG-N06CA
• Secondary ID: NCI-2011-01768CD
• Status: Completed
• Phase: Phase 3
• First received: August 14, 2007
• Last updated: July 3, 2015
• Start date: February 2008
• Est. completion date: January 2010

Study information

• Verified date: July 2015
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Baclofen-amitriptyline-ketamine (BAK) gel may lessen peripheral neuropathy caused by chemotherapy. It is not yet known whether BAK gel is more effective than a placebo in treating peripheral neuropathy caused by chemotherapy .

PURPOSE: This randomized phase III trial is studying BAK gel to see how well it works compared with a placebo in treating peripheral neuropathy caused by chemotherapy in patients with cancer.

Description:

OBJECTIVES:

Primary

• Compare the effectiveness of baclofen-amitriptyline hydrochloride-ketamine (BAK) gel versus placebo, in terms of improving sensory neuropathy, in cancer patients with chemotherapy-induced peripheral neuropathy.

Secondary

• Compare motor and autonomic symptoms and functioning, mood states, pain, and peripheral neuropathy in these patients.

• Assess the adverse event profile of topical BAK gel.

• Explore whether topical BAK gel is absorbed systemically.

OUTLINE: Patients are stratified according to neurotoxic chemotherapy (active vs non-active), current use of opioids or oral pain medications (yes vs no), pain rating (4-7 vs 8-10), and prior ineffective pharmacologic treatment for peripheral neuropathy (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients apply 1 spoonful of baclofen-amitriptyline hydrochloride-ketamine gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks.

• Arm II: Patients apply 1 spoonful of placebo gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks.

Some patients in both arms may choose to continue on the active gel or, if on placebo, begin the active gel for an additional 8 weeks off study.

Patients complete health, pain, mood, and quality of life questionnaires at baseline and periodically during study. Patients also record adverse symptoms weekly in a Symptom Experience Diary.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 211
• Est. completion date: January 2010
• Est. primary completion date: April 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Diagnosis of cancer

• Received or currently receiving neurotoxic chemotherapy including, but not limited to, taxanes (e.g., paclitaxel or docetaxel); platinum-based compounds (e.g., carboplatin, cisplatin, or oxaliplatin); vinca alkaloids (e.g., vincristine or vinblastine); or other neurotoxic chemotherapy agents (e.g., bortezomib, lenalidomide, or thalidomide)

• Must have pain or symptoms of peripheral neuropathy attributable to chemotherapy for = 1 month

• Neuropathy is limited to either hands and/or feet where gel can be applied

• Neuropathic pain score of = 4 out of 10 on the numbness/tingling/pain numeric analogue scale

• No pre-existing or history of peripheral neuropathy due to any cause other than chemotherapy (e.g., diabetes, alcohol, toxin, heredity)

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2

• Life expectancy = 4 months

• Creatinine = 1.5 times upper limit of normal

• Not pregnant or nursing

• No ability to bear children defined by 1 of the criteria:

• Menopausal (12 months and no menstrual period if natural menopause)

• Underwent a hysterectomy and/or oophorectomy

• Permanent surgical sterilization (tubal ligation)

• Fertile patients must use effective contraception

• Able to complete questionnaires independently or with assistance

• Able to sign informed consent and understand the nature of a placebo-controlled trial

• No history of an allergic reaction to baclofen, amitriptyline hydrochloride, and/or ketamine

• No diagnosis of any New York Heart Association class I-IV congestive heart failure

• No diagnosis of coronary artery disease including, but not limited to, myocardial infarction, within the past 5 years

• No other medical condition that, in the opinion of the treating physician or allied health professional, would make this clinical trial unreasonably hazardous for the patient

• No skin abnormalities at the intended application sites (hands and feet) of study gel (i.e., skin breakdown)

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• More than 30 days since prior anticonvulsants, tricyclic antidepressants, monoamine oxidase inhibitor, or other neuropathic pain medication (e.g., carbamazepine, phenytoin, valproic acid, gabapentin, lamotrigine, topical lidocaine patch or gel, capsaicin cream, or amifostine)

• Patients treated with any of these agents for peripheral neuropathy for = 1 week during the past 30 days are eligible provided they are no longer taking the agent

• More than 5 years since prior percutaneous transluminal coronary angioplasty or coronary artery bypass graft

• Prior heart valve replacement surgery allowed provided patient has fully recovered from the surgery

• No concurrent use of study agents other than as specified in the trial

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Chronic Myeloproliferative Disorders
• Disease
• Leukemia
• Lymphoma
• Lymphoproliferative Disorder
• Lymphoproliferative Disorders
• Multiple Myeloma
• Multiple Myeloma and Plasma Cell Neoplasm
• Myelodysplastic Syndromes
• Myelodysplastic-Myeloproliferative Diseases
• Myelodysplastic/Myeloproliferative Neoplasms
• Myeloproliferative Disorders
• Neoplasms
• Neoplasms, Plasma Cell
• Neurotoxicity
• Neurotoxicity Syndromes
• Pain
• Peripheral Nervous System Diseases
• Plasmacytoma
• Preleukemia
• Unspecified Adult Solid Tumor, Protocol Specific

Intervention

Drug:
• baclofen/amitriptyline/ketamine gel
Applied topically

Other:
• placebo
Applied topically

Locations

Country	Name	City	State
United States	Hickman Cancer Center at Bixby Medical Center	Adrian	Michigan
United States	McFarland Clinic, PC	Ames	Iowa
United States	AnMed Cancer Center	Anderson	South Carolina
United States	Rush-Copley Cancer Care Center	Aurora	Illinois
United States	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana
United States	Mary Rutan Hospital	Bellefontaine	Ohio
United States	MeritCare Bemidji	Bemidji	Minnesota
United States	Billings Clinic - Downtown	Billings	Montana
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana
United States	Northern Rockies Radiation Oncology Center	Billings	Montana
United States	St. Vincent Healthcare Cancer Care Services	Billings	Montana
United States	Bismarck Cancer Center	Bismarck	North Dakota
United States	Medcenter One Hospital Cancer Care Center	Bismarck	North Dakota
United States	Mid Dakota Clinic, PC	Bismarck	North Dakota
United States	St. Alexius Medical Center Cancer Center	Bismarck	North Dakota
United States	St. Joseph Medical Center	Bloomington	Illinois
United States	Wood County Oncology Center	Bowling Green	Ohio
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	St. James Healthcare Cancer Care	Butte	Montana
United States	Graham Hospital	Canton	Illinois
United States	Memorial Hospital	Carthage	Illinois
United States	Cedar Rapids Oncology Associates	Cedar Rapids	Iowa
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	North Coast Cancer Care - Clyde	Clyde	Ohio
United States	CCOP - Columbus	Columbus	Ohio
United States	Doctors Hospital at Ohio Health	Columbus	Ohio
United States	Grant Medical Center Cancer Care	Columbus	Ohio
United States	Mount Carmel Health - West Hospital	Columbus	Ohio
United States	Riverside Methodist Hospital Cancer Care	Columbus	Ohio
United States	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota
United States	Geisinger Cancer Institute at Geisinger Health	Danville	Pennsylvania
United States	CCOP - Dayton	Dayton	Ohio
United States	Good Samaritan Hospital	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Samaritan North Cancer Care Center	Dayton	Ohio
United States	Grady Memorial Hospital	Delaware	Ohio
United States	CCOP - Duluth	Duluth	Minnesota
United States	Duluth Clinic Cancer Center - Duluth	Duluth	Minnesota
United States	Miller - Dwan Medical Center	Duluth	Minnesota
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Elkhart General Hospital	Elkhart	Indiana
United States	Hematology Oncology Center	Elyria	Ohio
United States	Eureka Community Hospital	Eureka	Illinois
United States	CCOP - MeritCare Hospital	Fargo	North Dakota
United States	MeritCare Broadway	Fargo	North Dakota
United States	Blanchard Valley Medical Associates	Findlay	Ohio
United States	Middletown Regional Hospital	Franklin	Ohio
United States	Fredericksburg Oncology, Incorporated	Fredericksburg	Virginia
United States	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota
United States	Galesburg Clinic, PC	Galesburg	Illinois
United States	Galesburg Cottage Hospital	Galesburg	Illinois
United States	Altru Cancer Center at Altru Hospital	Grand Forks	North Dakota
United States	Big Sky Oncology	Great Falls	Montana
United States	Great Falls Clinic - Main Facility	Great Falls	Montana
United States	Sletten Cancer Institute at Benefis Healthcare	Great Falls	Montana
United States	Legacy Mount Hood Medical Center	Gresham	Oregon
United States	Mason District Hospital	Havana	Illinois
United States	Geisinger Hazleton Cancer Center	Hazleton	Pennsylvania
United States	Hopedale Medical Complex	Hopedale	Illinois
United States	Mayo Clinic - Jacksonville	Jacksonville	Florida
United States	Joliet Oncology-Hematology Associates, Limited - West	Joliet	Illinois
United States	Glacier Oncology, PLLC	Kalispell	Montana
United States	Kalispell Medical Oncology at KRMC	Kalispell	Montana
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Charles F. Kettering Memorial Hospital	Kettering	Ohio
United States	Howard Community Hospital	Kokomo	Indiana
United States	Franciscan Skemp Healthcare - La Crosse Campus	La Crosse	Wisconsin
United States	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana
United States	Haematology-Oncology Associates of Ohio and Michigan, PC	Lambertville	Michigan
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Lima Memorial Hospital	Lima	Ohio
United States	Cancer Resource Center - Lincoln	Lincoln	Nebraska
United States	McDonough District Hospital	Macomb	Illinois
United States	Immanuel St. Joseph's	Mankato	Minnesota
United States	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota
United States	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio
United States	Northwest Ohio Oncology Center	Maumee	Ohio
United States	St. Luke's Hospital	Maumee	Ohio
United States	Saint Anthony Memorial Health Centers	Michigan City	Indiana
United States	Providence Milwaukie Hospital	Milwaukie	Oregon
United States	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota
United States	Community Medical Center	Missoula	Montana
United States	Guardian Oncology and Center for Wellness	Missoula	Montana
United States	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana
United States	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana
United States	Community Cancer Center of Monroe	Monroe	Michigan
United States	Mercy Memorial Hospital - Monroe	Monroe	Michigan
United States	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio
United States	Community Cancer Center	Normal	Illinois
United States	Alegant Health Cancer Center at Bergan Mercy Medical Center	Omaha	Nebraska
United States	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Immanuel Medical Center	Omaha	Nebraska
United States	St. Charles Mercy Hospital	Oregon	Ohio
United States	Toledo Clinic - Oregon	Oregon	Ohio
United States	Community Hospital of Ottawa	Ottawa	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois
United States	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois
United States	OSF St. Francis Medical Center	Peoria	Illinois
United States	Proctor Hospital	Peoria	Illinois
United States	Illinois Valley Community Hospital	Peru	Illinois
United States	Adventist Medical Center	Portland	Oregon
United States	CCOP - Columbia River Oncology Program	Portland	Oregon
United States	Legacy Emanuel Hospital and Health Center and Children's Hospital	Portland	Oregon
United States	Legacy Good Samaritan Hospital & Comprehensive Cancer Center	Portland	Oregon
United States	Providence Cancer Center at Providence Portland Medical Center	Portland	Oregon
United States	Providence St. Vincent Medical Center	Portland	Oregon
United States	Perry Memorial Hospital	Princeton	Illinois
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Reid Hospital & Health Care Services	Richmond	Indiana
United States	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Rutherford Hospital	Rutherfordton	North Carolina
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	Park Nicollet Cancer Center	Saint Louis Park	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	North Coast Cancer Care, Incorporated	Sandusky	Ohio
United States	Guthrie Cancer Center at Guthrie Clinic Sayre	Sayre	Pennsylvania
United States	Mayo Clinic Scottsdale	Scottsdale	Arizona
United States	Mercy Medical Center - Sioux City	Sioux City	Iowa
United States	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa
United States	St. Luke's Regional Medical Center	Sioux City	Iowa
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Medical X-Ray Center, PC	Sioux Falls	South Dakota
United States	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota
United States	CCOP - Northern Indiana CR Consortium	South Bend	Indiana
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Saint Joseph Regional Medical Center	South Bend	Indiana
United States	CCOP - Upstate Carolina	Spartanburg	South Carolina
United States	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina
United States	St. Margaret's Hospital	Spring Valley	Illinois
United States	Community Hospital of Springfield and Clark County	Springfield	Ohio
United States	Mercy Medical Center	Springfield	Ohio
United States	Lakeland Regional Cancer Care Center - St. Joseph	St. Joseph	Michigan
United States	Geisinger Medical Group - Scenery Park	State College	Pennsylvania
United States	Flower Hospital Cancer Center	Sylvania	Ohio
United States	Mercy Hospital of Tiffin	Tiffin	Ohio
United States	CCOP - Toledo Community Hospital	Toledo	Ohio
United States	Medical University of Ohio Cancer Center	Toledo	Ohio
United States	St. Anne Mercy Hospital	Toledo	Ohio
United States	St. Vincent Mercy Medical Center	Toledo	Ohio
United States	Toledo Clinic, Incorporated - Main Clinic	Toledo	Ohio
United States	Toledo Hospital	Toledo	Ohio
United States	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio
United States	Legacy Meridian Park Hospital	Tualatin	Oregon
United States	Carle Cancer Center at Carle Foundation Hospital	Urbana	Illinois
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	Southwest Washington Medical Center Cancer Center	Vancouver	Washington
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Fulton County Health Center	Wauseon	Ohio
United States	Mount Carmel St. Ann's Cancer Center	Westerville	Ohio
United States	Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center	Wilkes-Barre	Pennsylvania
United States	Mercy Hospital at Wilkes-Barre	Wilkes-Barre	Pennsylvania
United States	Willmar Cancer Center at Rice Memorial Hospital	Willmar	Minnesota
United States	Clinton Memorial Hospital	Wilmington	Ohio
United States	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota
United States	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio
United States	Genesis - Good Samaritan Hospital	Zanesville	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (4)

Barton DL, Wos E, Qin R, et al.: A randomized controlled trial evaluating a topical treatment for chemotherapy-induced neuropathy: NCCTG trial N06CA. [Abstract] J Clin Oncol 27 (Suppl 15): A-9531, 2009.

Barton DL, Wos EJ, Qin R, Mattar BI, Green NB, Lanier KS, Bearden JD 3rd, Kugler JW, Hoff KL, Reddy PS, Rowland KM Jr, Riepl M, Christensen B, Loprinzi CL. A double-blind, placebo-controlled trial of a topical treatment for chemotherapy-induced peripheral — View Citation

Wolf SL, Barton DL, Qin R, Wos EJ, Sloan JA, Liu H, Aaronson NK, Satele DV, Mattar BI, Green NB, Loprinzi CL. The relationship between numbness, tingling, and shooting/burning pain in patients with chemotherapy-induced peripheral neuropathy (CIPN) as meas — View Citation

Wolf SL, Qin R, Barton DL, et al.: Relationship of sensory symptoms and motor function in patients with chemotherapy-induced peripheral neuropathy (CIPN) utilizing the EORTC QLQ CIPN20: NCCTG study N06CA. [Abstract] J Clin Oncol 27 (Suppl 15): A-9587, 200

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total sensory neuropathy (area under the curve [AUC]) as measured by the EORTC QLQ-CIPN20 at baseline and week 4		Up to 4 weeks	No
Secondary	Motor neuropathy as measured by the EORTC QLQ-CIPN20 at baseline and week 4		Up to 4 weeks	No
Secondary	Autonomic symptoms and functioning as measured by the EORTC QLQ-CIPN20 at baseline and week 4		Up to 4 weeks	No
Secondary	Mood states and total mood disturbance as measured by the Profile of Mood States-Brief at baseline and week 4		Up to 4 weeks	No
Secondary	Pain severity and interference as measured by the Brief Pain Inventory at baseline and week 4		Up to 4 weeks	No
Secondary	Numbness, tingling, and pain as measured by the Peripheral Neuropathy Questionnaire at baseline and weekly for 4 weeks		Up to 4 weeks	No
Secondary	Perception of benefit as measured by the Subject Global Impression of Change at the end of week 4		Up to 4 weeks	No
Secondary	Frequency and severity of adverse events reported by the patient in the Symptom Experience Diary and evaluated through clinical assessment by NCI CTCAE v3.0		Up to 4 weeks	Yes