Chemotherapy induced peripheral neuropathy MedDRA version: 20.1 Level: LLT Classification code 10079545 Term: Chemotherapy induced peripheral neuropathy System Organ Class: 100000004852
Conditions
Sponsors
PledPharma AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed informed consent form before any study related assessments and willing to follow all study procedures. 2. Male or female aged =18 years. 3. Pathologically confirmed adenocarcinoma of the colon or rectum including: Stage III carcinoma (any T N1,2 M0) or Stage II carcinoma (T3,4 N0 M0). 4. The patient has undergone curative (R0) surgical resection performed not less than 28 days and generally not more than 8-12 weeks prior to randomization. 5. The patient has a postsurgical CEA level =1.5 x upper limit of normal (ULN, in current smokers, CEA level =2.0 x ULN is allowed). 6. No prior anti-cancer therapy for CRC except radiotherapy or concomitant chemoradiotherapy using a fluoropyrimidine alone for locoregional rectal cancer. 7. Patient indicated for up to 6 months of oxaliplatin-based chemotherapy and without any clinically observed neurological disorders. 8. ECOG performance status of 0 or 1. 9. Adequate hematological parameters: hemoglobin =100 g/L, absolute neutrophil count (ANC) =1.5 x 109 /L, platelets =100 x 109 /L. 10. Adequate renal function: creatinine clearance >50 cc/min using the Cockroft and Gault formula or measured. 11. Adequate hepatic function: total bilirubin =1.5 x ULN (except in the case of known Gilbert’s syndrome); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =3 x ULN (AST and ALT =5 x ULN in case of liver metastases). 12. Baseline blood Mn level =65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
Exclusion criteria: 1. Any evidence of metastatic disease. 2. Any unresolved toxicity by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v.4.03) >Grade 1 from previous anti-cancer therapy (including radiotherapy), except alopecia. 3. Any grade of neuropathy from any cause. 4. Any prior oxaliplatin-based chemotherapy <1 year before the randomization. 5. Any evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory, cardiac, unresolved bowel obstruction, hepatic or renal disease). 6. Chronic infection or uncontrolled serious illness causing immunodeficiency. 7. Recent (<28 days) surgery prior to entry into the study or a surgical incision that is not fully healed. 8. Known hypersensitivity to any of the components of mFOLFOX6 and, if applicable, therapies to be used in conjunction with the chemotherapy regimen or any of the excipients of these products. 9. History of other malignancies (except for adequately treated basal or squamous cell carcinoma or carcinoma in situ) within 5 years, unless the patient has been disease free for that other malignancy for at least 2 years. 10. Known dihydropyrimidine dehydrogenase deficiency. 11. Pre-existing neurodegenerative disease (e.g., Parkinson’s, Alzheimer’s, Huntington’s) or neuromuscular disorder (e.g., multiple sclerosis, amyotrophic lateral sclerosis, polio, hereditary neuromuscular disease). 12. Major psychiatric disorder (major depression, psychosis), alcohol and/or drug abuse. 13. Patients with a history of second or third degree atrioventricular block or a family heredity. 14. A history of a genetic or familial neuropathy. 15. Treatment with any investigational drug within 30 days prior to randomization. 16. Pregnancy, lactation or reluctance to using contraception. 17. Any other condition that, in the opinion of the Investigator, places the patient at undue risk. 18. Previous exposure to mangafodipir or calmangafodipir. 19. Welders, mine workers or other workers in occupations (current or past) where high Mn exposure is likely.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare PledOx (5 µmol/kg) vs placebo with respect to the proportion of patients with moderate or severe chronic CIPN;Secondary Objective: To compare PledOx vs placebo: Efficacy • The proportion of patients with mild, moderate or severe chronic CIPN • The sensitivity to touching cold items • The cumulative dose of oxaliplatin during chemotherapy • The vibration sensitivity on the lateral malleolus • The worst pain in hands or feet • The functional impairment (in the non-dominant hand) • The sustained efficacy on prevention of CIPN during long-term follow-up Safety • DFS • Safety and tolerability Exploratory • Chronic CIPN by supporting analysis using the full FACT/GOG NTX-13 • The cumulative dose of 5-FU during chemotherapy • For both oxaliplatin and 5-FU: Dose intensity, number of cycles, dose reductions, reason(s) for dose reductions, patients with dose delays, and length of dose delays • Quality of Life/health status • The functional impairment (in the non-dominant hand) during long-term follow-up • The worst pain in hands or feet during long-term follow-up. • Health economic impact;Primary end point(s): Proportion of patients scoring 3 or 4, derived as the maximum score of items NTX 1 to 4, in any of the symptoms of numbness, tingling and discomfort in hands and feet in the FACT/GOG-NTX-13, 9 months after the first dose. ;Timepoint(s) of evaluation of this end point: 9 months after first dose of IMP | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Endpoints Efficacy • Proportion of patients (with mild, moderate or severe chronic CIPN) scoring 2, 3, or 4, in at least 1 of the first 4 items of the FACT/GOG-NTX-13 (i.e. FACT/GOG-NTX-4), targeting numbness, tingling or discomfort in hands and/or feet, 9 months after the first dose of IMP • Mean change from baseline in sensitivity to touching cold items on Day 2, Cycle 4 of mFOLFOX6 chemotherapy, as assessed by the Cold Sensitivity questionnaire • Mean cumulative dose of oxaliplatin administered per patient during mFOLFOX6 chemotherapy, 9 months after the first dose of IMP • Mean change from baseline in vibration sense, on the lateral malleolus (left and right), using a graduated tuning fork, at 9 months after the first dose of IMP • Mean change from baseline in worst pain in hands or feet in the past week, using a numerical rating scale (NRS), at 9 months after the first dose of IMP • Mean change from baseline in the time to complete the grooved Pegboard with the non-dominant hand, at 9 months after the first dose of IMP • Proportion of patients scoring 3 or 4 in at least 1 of the first 4 items of the FACT/GOG-NTX-13 (i.e. FACT/GOG-NTX-4), targeting numbness, tingling or discomfort in hands and/or feet, 12, 18, and 24 months after the first dose of IMP Safety • DFS • Safety and tolerability as assessed by adverse events (AEs), laboratory variables and vital signs Exploratory Endpoints • Frequency and proportion of patients with any CIPN scoring 1, 2, 3 or 4, in any of the first 4 items of the FACT/GOG-NTX-13 (i.e. FACT/GOG-NTX-4), targeting numbness, tingling or discomfort in hands and/or feet, at all other timepoints after the first dose of IMP • Mean score of the first 4 items of the FACT/GOG-NTX-13 (i.e. FACT/GOG-NTX-4), at 9 months after the first dose of IMP • Mean score of the 13 items of the FACT/GOG-NTX-13, at 9 months after the first dose of IMP • Mean cumulative dose of 5-FU administered per patient d | — |
Countries
Belgium, France, Germany, Spain, United Kingdom
Contacts
Public ContactChief Medical Officer
PledPharma AB
Outcome results
None listed