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

Sponsors and Collaborators:	North Central Cancer Treatment Group National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00516503

Purpose

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.

Condition	Intervention	Phase
Cancer-Related Problem/Condition Chronic Myeloproliferative Disorders Leukemia Lymphoma Lymphoproliferative Disorder Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases Pain Unspecified Adult Solid Tumor, Protocol Specific	Drug: baclofen/amitriptyline/ketamine gel Drug: placebo	Phase III

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Cancer Fungal Infections Hodgkin's Disease Leukemia, Adult Acute Leukemia, Adult Chronic Lymphoma Multiple Myeloma Peripheral Nerve Disorders

Drug Information available for: Amitriptyline Amitriptyline hydrochloride Baclofen Ketamine Ketamine hydrochloride

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Supportive Care, Randomized, Double-Blind, Placebo Control
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

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Total sensory neuropathy (area under the curve [AUC]) as measured by the EORTC QLQ-CIPN20 at baseline and week 4 [ Designated as safety issue: No ]

Secondary Outcome Measures:

Motor neuropathy as measured by the EORTC QLQ-CIPN20 at baseline and week 4 [ Designated as safety issue: No ]
Autonomic symptoms and functioning as measured by the EORTC QLQ-CIPN20 at baseline and week 4 [ Designated as safety issue: No ]
Mood states and total mood disturbance as measured by the Profile of Mood States-Brief at baseline and week 4 [ Designated as safety issue: No ]
Pain severity and interference as measured by the Brief Pain Inventory at baseline and week 4 [ Designated as safety issue: No ]
Numbness, tingling, and pain as measured by the Peripheral Neuropathy Questionnaire at baseline and weekly for 4 weeks [ Designated as safety issue: No ]
Perception of benefit as measured by the Subject Global Impression of Change at the end of week 4 [ Designated as safety issue: No ]
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 [ Designated as safety issue: Yes ]

Estimated Enrollment:	148
Study Start Date:	February 2008
Estimated Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I: Experimental 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.	Drug: baclofen/amitriptyline/ketamine gel Applied topically
Arm II: Placebo Comparator 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.	Drug: placebo Applied topically

Detailed 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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00516503

Show 178 Study Locations

Sponsors and Collaborators

North Central Cancer Treatment Group

National Cancer Institute (NCI)

Investigators

Study Chair:

Debra Barton, RN, PhD, AOCN

Mayo Clinic

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000560732, NCCTG-N06CA
Study First Received:	August 14, 2007
Last Updated:	January 15, 2009
ClinicalTrials.gov Identifier:	NCT00516503
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

unspecified adult solid tumor, protocol specific
neurotoxicity
pain
accelerated phase chronic myelogenous leukemia
acute undifferentiated leukemia
adult acute lymphoblastic leukemia in remission
adult acute myeloid leukemia in remission
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
atypical chronic myeloid leukemia
blastic phase chronic myelogenous leukemia
chronic myelomonocytic leukemia

chronic phase chronic myelogenous leukemia
mast cell leukemia
meningeal chronic myelogenous leukemia
progressive hairy cell leukemia, initial treatment
prolymphocytic leukemia
recurrent adult acute lymphoblastic leukemia
recurrent adult acute myeloid leukemia
recurrent adult T-cell leukemia/lymphoma
refractory chronic lymphocytic leukemia
refractory hairy cell leukemia
relapsing chronic myelogenous leukemia
secondary acute myeloid leukemia
stage 0 chronic lymphocytic leukemia
stage I adult T-cell leukemia/lymphoma
stage I chronic lymphocytic leukemia

Study placed in the following topic categories:

Blast Crisis
Sezary syndrome
Chronic myelogenous leukemia
Hodgkin lymphoma, adult
Lymphoma, small cleaved-cell, diffuse
Small non-cleaved cell lymphoma
Lymphoma, large-cell, immunoblastic
Lymphomatoid granulomatosis
Preleukemia
Leukemia, Prolymphocytic
Hemorrhagic Disorders
Hemorrhagic thrombocythemia
Lymphoma, Large-Cell, Anaplastic
Neoplasm Metastasis
Thrombocythemia, Hemorrhagic

Myelodysplastic syndromes
Essential thrombocytosis
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Hematologic Diseases
Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
Leukemia, Myelomonocytic, Chronic
Blood Coagulation Disorders
Acute myelogenous leukemia
Leukemia, Myeloid
Myelodysplastic myeloproliferative disease
Waldenstrom Macroglobulinemia
Plasmacytoma
Leukemia, Myeloid, Accelerated Phase
HIV Infections
B-cell lymphomas

Additional relevant MeSH terms:

Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Adrenergic Agents
Molecular Mechanisms of Pharmacological Action
Adrenergic Uptake Inhibitors
Physiological Effects of Drugs
Psychotropic Drugs
Anesthetics
Excitatory Amino Acid Agents
Neuromuscular Agents
Pathologic Processes
Sensory System Agents
Therapeutic Uses
Syndrome
Muscle Relaxants, Central

Cardiovascular Diseases
Analgesics
Antidepressive Agents
Excitatory Amino Acid Antagonists
Anesthetics, Intravenous
Neoplasms by Histologic Type
Disease
Immune System Diseases
Nervous System Diseases
Central Nervous System Depressants
Anesthetics, Dissociative
Pharmacologic Actions
Antidepressive Agents, Tricyclic
Neoplasms
Anesthetics, General

ClinicalTrials.gov processed this record on January 16, 2009