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

• Duration Adjusted Average Change (DAAC) of Paresthesic Symptom Score Within Each Cycle of Chemotherapy Measured by Numeric Rating Scale (NRS) [ Time Frame: Baseline to Cycle 9 ] [ Designated as safety issue: No ]
• Duration Adjusted Average Change (DAAC) of Dysesthesia Symptom Score Within Each Cycle of Chemotherapy Measured by Numeric Rating Scale (NRS) [ Time Frame: Baseline to Cycle 9, LOCF cycle endpoint ] [ Designated as safety issue: No ]
• Duration Adjusted Average Change (DAAC) of Pain Symptom Score Within Each Cycle of Chemotherapy Measured by Numeric Rating Scale (NRS) [ Time Frame: Baseline to Cycle 9, LOCF cycle endpoint ] [ Designated as safety issue: No ]
• Change in Pain Scores Rated on Neuropathic Pain Symptom Inventory (NPSI) Subscales From Baseline Cycle [ Time Frame: Baseline to Cycle 9, Last Observation Carried Forward (LOCF) cycle endpoint ] [ Designated as safety issue: No ]
• Number of Participants With Persistent Paresthesic, Dysesthesic, and Pain Symptoms [ Time Frame: Cycle 9 and Last Observation Carried Forward (LOCF) cycle endpoint ] [ Designated as safety issue: No ]

• Time to onset of any paresthesic positive symptoms of the chemotherapy-induced neuropathy from the onset of chemotherapy
• Time to onset of persistent dysesthesic and pain positive symptoms of chemotherapy-induced neuropathy from time of initial chemotherapy, as measured using the modified NRS
• Time to onset of acute positive neuropathic symptoms (paresthesia, dysesthesia and pain) of the chemotherapy-induced neuropathy from time of initial chemotherapy
• Severity of parasthesic, dysesthesic, and pain symptom scores over each chemotherapy cycle
• Proportion of subjects experiencing positive neuropathic symptoms in each treatment group at endpoint
• Time to onset of the chemotherapy-induced cold intolerance developed from time of initial chemotherapy
• Change in pain interference of function from baseline to endpoint as measured by the mBPI-SF (modified Brief Pain Inventory Short Form)
• Change in sleep interference in subjects with chemotherapy- induced peripheral neuropathy from baseline to endpoint as measured by the Sleep Interference scale
• Change in self-reported symptoms of depression and anxiety in subjects with chemotherapy induced peripheral neuropathy from baseline to endpoint as measured by the Hospital Anxiety and Depression Scale (HADS)
• Overall health status as measured by the EuroQol (EQ-5D) Health State Profile Questionnaire at endpoint
• Safety and tolerability of pregabalin for the treatment of subjects with pain associated with chemotherapy-induced neuropathy
• Percentage of subjects who require dose reduction or discontinue chemotherapy
• The safety of pregabalin will be assessed using Adverse Event (AE) monitoring throughout the trial, Physical Examinations
• and vital signs at screening and endpoint and laboratory testing including hematology, chemistry, urinalysis and pregnancy at each visit,
• and 12-Lead ECG at screening.

Prevention and treatment of the severity of symptoms of chemotherapy-induced peripheral neuropathy.

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.

• Drug: Pregabalin
  150- 600 mg/day (double blind in divided doses)
  Other Name: Chemotherapy
• Drug: Placebo
  Placebo
  Other Name: Chemotherapy

• Experimental: 1
  flexible dosing
  Intervention: Drug: Pregabalin
• Placebo Comparator: 2
  Intervention: Drug: Placebo

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