Neuropathic Pain in Patients With Cancer

A Phase 2 Double-Blind Dose Escalation Study of KRN5500 for Neuropathic Pain in Patients With Cancer

The purpose of this study is to collect beginning information on whether intravenous (IV) administration of KRN5500 is safe and effective for treatment of neuropathic pain in patients with cancer.

Study Overview

• Status: Completed
• Conditions: Neuropathic Pain
• Intervention / Treatment: Drug: KRN5500; Drug: Placebo

Detailed Description

Neuropathic pain is a type of pain that results from nerve damage and is characterized by an abnormal hypersensitivity to harmless as well as harmful stimuli. This type of pain is extremely difficult to manage, fails to respond to standard analgesic medications or interventions, and often gets worse instead of better over time. Current approved therapeutic agents often have intolerable side effects and limited efficacy. Thus, there is an urgent need to develop safe and effective drugs to treat neuropathic pain.

Study DTCL100 will be conducted at multiple centers and will enroll patients that have advanced cancer AND neuropathic pain that has not responded well to previous treatment. Eighteen patients will be randomly assigned to receive up to 8 doses of active drug (KRN5500) or placebo. A maximum of 8 doses will be administered weekly over a 10 week period. Patients are encouraged to complete at least 4 treatment visits before a decision is made to complete the full 10 weeks of treatment and the 1 month followup period.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2

Contacts and Locations

Study Locations

• Puerto Rico
  • Rio Piedras, Puerto Rico, 00921
    • Dr. Rivera-Colon
• United States
  • California
    • Los Angeles, California, United States, 90025
      • Cancer Institute Medical Group
    • Los Angeles, California, United States, 90027
      • Ghassan Al-Jazayrly, M.D., Inc.
    • Orange, California, United States, 92868
      • University of California / Irvine Chao Family Comprehensive Cancer Center
  • Florida
    • Jupiter, Florida, United States, 33477
      • Keog Pharma, Inc.
  • Louisiana
    • Covington, Louisiana, United States, 70433
      • Hematology And Oncology Specialists, Llc
  • Maryland
    • Baltimore, Maryland, United States, 21229
      • St. Agnes Healthcare, Inc
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • New Jersey
    • East Orange, New Jersey, United States, 07018
      • East Orange VA Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Winston-Salem, North Carolina, United States, 27103
      • Carolina Pain Institute, PA
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18 years or older
• Diagnosis of advanced or recurrent cancer
• No options for curative chemotherapy, but palliative chemotherapy allowed under certain conditions
• Refractory neuropathic pain rated 4 or greater on 0-10 scale and failure to respond to 2 commonly used treatments
• If taking opioids for pain, stable regimen over past week before enrolling
• Karnofsky performance status of 40 or more
• Females must be sterile or post-menopausal

Exclusion Criteria:

• Radiation to site of neuropathic pain for past 4 weeks
• Major surgery within past 2 weeks
• Liver function and other key labs outside normal parameters
• ECG showing significant abnormality
• Myocardial Infarction (heart attack) within past 6 months
• History of interstitial lung disease
• History of severe allergic reaction to drugs containing polysorbate 80
• Other investigational drug within 2 weeks or 5 half-lives (whichever is longer

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: KRN5500; KRN5500 escalating dose of .6, 1.2, 1.8, or 2.2 mg/m2 in IV infusion of normal saline	Drug: KRN5500; Patients are seen weekly and dosed for pain with IV medication of active drug/KRN5500 or placebo . The dose can be escalated, from .6 mg/m2, to 1.2, 1.8, and 2.2 mg/m2.
Placebo Comparator: Normal Saline; Placebo consists of IV infusion of normal saline	Drug: KRN5500; Patients are seen weekly and dosed for pain with IV medication of active drug/KRN5500 or placebo . The dose can be escalated, from .6 mg/m2, to 1.2, 1.8, and 2.2 mg/m2.; Drug: Placebo; Normal Saline given as dose escalation for placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Average pain intensity over the previous 24 hours as measured by a numeric rating scale (NRS) ranging from 0 to 10 where 0 represents "no pain" and 10 represents the "worst possible pain."	Weekly for 10 weeks plus 30 day followup

Secondary Outcome Measures

Outcome Measure	Time Frame
Physical Examination, Vital signs and body weight, Electrocardiogram, Laboratory parameters, Adverse events, Clinical Opiate Withdrawal Scale, rescue medication, Proportion of patients who achieved a 33% reduction in pain intensity	Weekly for 10 weeks plus 30 day followup

Collaborators and Investigators

• Sponsor: DARA Therapeutics
• Investigators: Principal Investigator: Richard Penson, MD, MRCP, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start: June 1, 2006
• Primary Completion (Actual): March 1, 2009
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: May 15, 2007
• First Submitted That Met QC Criteria: May 15, 2007
• First Posted (Estimate): May 17, 2007

Study Record Updates

• Last Update Posted (Estimate): August 16, 2010
• Last Update Submitted That Met QC Criteria: August 13, 2010
• Last Verified: August 1, 2010

More Information

Terms related to this study

• Keywords: Cancer; Neuropathic pain
• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Neuromuscular Diseases; Peripheral Nervous System Diseases; Neuralgia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Synthesis Inhibitors; KRN 5500
• Other Study ID Numbers: DTCL100