台灣臨床試驗主持人資料庫|TPIDB

Condition/Disease

Prevention of chemotherapy induced peripheral neuropathy (CIPN) (chemotherapy induced peripheral neuropathy)

Objectives

Comparing PledOx (5 µmol/kg) and placebo the proportion of patients with moderate or severe chronic CIPN

Test Drug

PledOx

Active Ingredient

calmangafodipir

Dosage Form

IV injection

Dosage

50 mM in 20 mL vial

Endpoints

"Main Test Index
• 9 months after the first dose of IMP (ie, PledOx or placebo administered on the first day of the first cycle of mFOLFOX6 chemotherapy), for numbness, tingling or discomfort in the hands and/or feet, in FACT/GOG-NTX- 13 The proportion of patients with at least one of the first 4 items (ie FACT/GOG-NTX-4) rated as 3 or 4 (moderate or severe chronic CIPN).
Secondary test index
Curative effect
• 9 months after the first dose of IMP, for numbness, tingling or discomfort in the hands and/or feet, at least one of the first 4 items of FACT/GOG-NTX-13 (ie FACT/GOG-NTX-4) Proportion of patients rated 2, 3, or 4 in 1 item (mild, moderate, or severe chronic CIPN)
• Use the cold sensitivity questionnaire to evaluate the average change in sensitivity and pain when touching cold objects from the baseline period to the second day of the 4th cycle of mFOLFOX6 chemotherapy
• During the mFOLFOX6 chemotherapy 9 months after the first dose of IMP, the average cumulative dose of Oxaliplatin administered to each patient
• Use a scaled tuning fork to measure the average change in vibration sensation from the baseline period to 9 months after the first dose of IMP at the lateral ankles (left and right feet).
• Use the Numerical Pain Rating Scale (NRS) to measure the average change in the most severe pain in the hands or feet in the past week from the baseline period to 9 months after the first dose of IMP
• The average change in the time required to complete the key-shaped hole board with non-dominant hands from the baseline period to 9 months after the first dose of IMP
• At 12, 18 and 24 months after the first dose of IMP, for numbness, tingling or discomfort in the hands and/or feet, the first 4 items of FACT/GOG-NTX-13 (ie FACT/GOG-NTX- 4) Proportion of patients with at least 1 item rated as 3 or 4
safety
• 12 and 24 months disease-free survival (DFS)
• Evaluate safety and tolerability based on adverse events (AE), laboratory test results and vital signs
• According to NCI-CTCAE 4.03 version, the proportion of patients with PledOx poisoning is added in addition to chemotherapy-related poisoning. "

Inclution 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 within 12 weeks prior to randomization.
5. The patient has a postsurgical CEA level ≤1.5x 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 chemo-radiotherapy using a fluoropyrimidine alone for locoregional rectal cancer.
7. Patient indicated for up to 6 months of oxaliplatin-based chemotherapy and without pathological findings of a neurologic exam performed prior to oxaliplatin treatment according to local practice.
8. ECOG performance status of 0 or 1.
9. Adequate hematological parameters: hemoglobin ≥100 g/L, ANC ≥1.5 x 109/L, platelets ≥100 x 109/L.
10. Adequate renal function: creatinine clearance >50 cc/min using the Cockcroft and Gault formula or measured.
11. Adequate hepatic function: total bilirubin ≤1.5 x ULN (except in the case of known Gilbert’s syndrome); AST and ALT ≤3 x ULN.
12. Baseline blood Mn level <2.0 x ULN.
13. For patients with a history of diabetes mellitus, HbA1c ≤7%.
14. Negative pregnancy test for WOCBP.
15. For men and WOCBP, use of adequate contraception (oral contraceptives, intrauterine device or surgically sterile) while on study drug and for at least 6 months after completion of study therapy.

Exclusion Criteria

"Main Test Index
• 9 months after the first dose of IMP (ie, PledOx or placebo administered on the first day of the first cycle of mFOLFOX6 chemotherapy), for numbness, tingling or discomfort in the hands and/or feet, in FACT/GOG-NTX- 13 The proportion of patients with at least one of the first 4 items (ie FACT/GOG-NTX-4) rated as 3 or 4 (moderate or severe chronic CIPN).
Secondary test index
Curative effect
• 9 months after the first dose of IMP, for numbness, tingling or discomfort in the hands and/or feet, at least one of the first 4 items of FACT/GOG-NTX-13 (ie FACT/GOG-NTX-4) Proportion of patients rated 2, 3, or 4 in 1 item (mild, moderate, or severe chronic CIPN)
• Use the cold sensitivity questionnaire to evaluate the average change in sensitivity and pain when touching cold objects from the baseline period to the second day of the 4th cycle of mFOLFOX6 chemotherapy
• During the mFOLFOX6 chemotherapy 9 months after the first dose of IMP, the average cumulative dose of Oxaliplatin administered to each patient
• Use a scaled tuning fork to measure the average change in vibration sensation from the baseline period to 9 months after the first dose of IMP at the lateral ankles (left and right feet).
• Use the Numerical Pain Rating Scale (NRS) to measure the average change in the most severe pain in the hands or feet in the past week from the baseline period to 9 months after the first dose of IMP
• The average change in the time required to complete the key-shaped hole board with non-dominant hands from the baseline period to 9 months after the first dose of IMP
• At 12, 18 and 24 months after the first dose of IMP, for numbness, tingling or discomfort in the hands and/or feet, the first 4 items of FACT/GOG-NTX-13 (ie FACT/GOG-NTX- 4) Proportion of patients with at least 1 item rated as 3 or 4
safety
• 12 and 24 months disease-free survival (DFS)
• Evaluate safety and tolerability based on adverse events (AE), laboratory test results and vital signs
• According to NCI-CTCAE 4.03 version, the proportion of patients with PledOx poisoning is added in addition to chemotherapy-related poisoning. "

Clinical Trials List

A Phase 3, double-blind, multicenter, placebo-controlled study of PledOx used on top of modified FOLFOX6 (5-FU/FA and Oxaliplatin) to prevent chemotherapy induced peripheral neuropathy (CIPN) in the adjuvant treatment of patients with Stage III or high-risk Stage II colorectal cancer

Investigators and Locations