Prevention And Treatment Of Chemotherapy-Induced Peripheral Neuropathy In Subjects With Advanced Colorectal Cancer

Study Overview
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Brief Summary
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Prevention and treatment of the severity of symptoms of chemotherapy-induced peripheral neuropathy.

Detailed Description
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This study was terminated on July 15, 2008. The results of an interim analysis showed that the conditional power to detect a difference in treatment groups was insufficient to warrant study continuation and therefore termination of the trial was recommended. The decision to terminate the trial was not based on safety concerns.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Trial Of The Prevention And Treatment Of Chemotherapy-Induced Peripheral Neuropathy Symptoms In Subjects With Advanced Colorectal Cancer

Conditions
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Chemotherapy-Induced Peripheral Neuropathy

Intervention / Treatment
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* Drug: Pregabalin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of cytological confirmed carcinoma of the Colon Stage III (Dukes C) or metastatic Colorectal Cancer (Dukes D) Independent of this protocol, the patient has decided to receive standard of care for the treatment of cancer with oxaliplatin combined with 5-fluorouracil/folinic acid (5-FU/FA) for a minimum of 9 cycles Exclusion Criteria: Presence of neuropathic pain or peripheral polyneuropathy or identified causes of painful paresthesia including radiotherapy-induced or malignant plexopathy, lumbar or cervical radiculopathy existing prior to baseline Any patients who are not suitable to be treated with either Oxaliplatin and/or 5-FU/FA or pregabalin according to the respective local labeling

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>flexible dosing | Drug: Pregabalin<br>* 150- 600 mg/day (double blind in divided doses)<br>* Other names: Chemotherapy;|
| Placebo Comparator: 2<br> | Drug: Placebo<br>* Placebo<br>* Other names: Chemotherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration Adjusted Average Change (DAAC) of Paresthesia From the Onset of Chemotherapy Measured by Numeric Rating Scale (NRS) | Least squares mean of change: mean at cycle minus mean at Baseline. Paresthetic duration Adjusted Average Change (DAAC) endpoint was computed based on Numeric Rating Scale (NRS) of paresthesia (collected 0=no pain; 1-3=mild pain; 4-6=moderate pain; 7-10=severe pain). DAAC endpoint is defined as the Area Under Curve (AUC) of the collected NRS over time, divided by the collection time period (up to 10 days). | Period of 10 days from the onset of chemotherapy to the last cycle: Last Observation Carried Forward (LOCF) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration Adjusted Average Change (DAAC) of Paresthesic Symptom Score Within Each Cycle of Chemotherapy Measured by Numeric Rating Scale (NRS) | Least squares mean of change: mean at cycle minus mean at Baseline. Paresthetic Duration Adjusted Average Change (DAAC) endpoint was computed based on Numeric Rating Scale (NRS) of paresthesia (collected 0=no pain; 1-3=mild pain; 4-6=moderate pain; 7-10=severe pain). DAAC endpoint is defined as the Area Under Curve (AUC) of the collected NRS over time, divided by collection time period (up to 10 days). | Baseline to Cycle 9 | 
| Duration Adjusted Average Change (DAAC) of Dysesthesia Symptom Score Within Each Cycle of Chemotherapy Measured by Numeric Rating Scale (NRS) | Least squares (LS) mean of change: mean at cycle minus mean at Baseline. Dysesthesic Duration Adjusted Average Change (DAAC) endpoint was computed based on Numeric Rating Scale (NRS) of dysesthesis (collected 0=no pain; 1-3=mild pain; 4-6=moderate pain; 7-10=severe pain). DAAC endpoint was defined as the Area Under Curve (AUC) of the collected NRS over time, divided by collection time period (up to 10 days). | Baseline to Cycle 9, LOCF cycle endpoint | 
| Duration Adjusted Average Change (DAAC) of Pain Symptom Score Within Each Cycle of Chemotherapy Measured by Numeric Rating Scale (NRS) | Least squares (LS) mean of change: mean at cycle minus mean at Baseline. Pain Duration Adjusted Average Change (DAAC) endpoint was computed based on Numeric Rating Scale (NRS) of pain (collected 0=no pain; 1-3=mild pain; 4-6=moderate pain; 7-10=severe pain). DAAC endpoint was defined as the Area Under Curve (AUC) of the collected NRS over time, divided by collection time period (up to 10 days). | Baseline to Cycle 9, LOCF cycle endpoint | 
| Change in Pain Scores Rated on Neuropathic Pain Symptom Inventory (NPSI) Subscales From Baseline Cycle | Least squares (LS) mean of change: mean at cycle minus mean at Baseline. Neuropathic Pain Symptom Inventory (NPSI) = questionnaire designed to evaluate symptoms of neuropathic pain. 11-point numeric rating scale, range: 0 (no pain) to 10 (worst pain imaginable) best describing their average pain for last 24 hours. | Baseline to Cycle 9, Last Observation Carried Forward (LOCF) cycle endpoint | 
| Number of Participants With Persistent Paresthesic, Dysesthesic, and Pain Symptoms | Number of participants with persistent paresthesic, dyesthesic, and pain symptoms at chemotherapy Cycle 9 and last observation carried forward (LOCF) endpoint. Numeric rating scale of symptoms: >=1: mild symptoms to >=4: moderate severe symptoms. Subjects rated their average severity of symptoms over the last 24 hours every evening before bedtime. | Cycle 9 and Last Observation Carried Forward (LOCF) cycle endpoint | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pain, chemotherapy