NCT03654729

Preventive Treatment of Oxaliplatin Induced Peripheral Neuropathy in Metastatic Colorectal Cancer (POLAR-M)

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 Patients With First-line mCRC

• Status: Terminated
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 291 (actual)
• Sponsor: Egetis Therapeutics · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study evaluates the investigational drug PledOx in the prevention of chronic chemotherapy induced peripheral neuropathy (CIPN) induced by the drug oxaliplatin.

Detailed description

Oxaliplatin, in combination with 5-fluorouracil plus folinate (or capecitabine), has increased survival in stage III colorectal cancer and prolonged life in stage IV patients, but its use is compromised because of severe toxicity. Chemotherapy-induced peripheral neuropathy (CIPN) is the most problematic dose-limiting toxicity of oxaliplatin. No treatments have been clinically proven to prevent CIPN. There is a body of evidence that CIPN is caused by cellular oxidative stress. Clinical and preclinical data suggest that the manganese chelate and superoxide dismutase mimetic mangafodipir (MnDPDP) and calmangafodipir (\[Ca0.8,Mn0.2\]Na3DPDP) are efficacious inhibitors of CIPN and other conditions caused by cellular oxidative stress, without interfering negatively with the tumoricidal activity of chemotherapy. This is a Phase 3, multicenter, double-blind, placebo-controlled study to establish the efficacious dose of PledOx in prevention of chronic CIPN induced by oxaliplatin. Patients with metastatic colorectal cancer (mCRC), who are indicated for first-line modified FOLFOX6 (mFOLFOX6) chemotherapy for at least 3 months, without any pre-planned treatment breaks, will be randomized in a 1:1:1 ratio, stratified by region (Asia, non-Asia) and PK sub-study (yes, no), to one of three treatment arms: * Arm A: PledOx (2 µmol/kg) + mFOLFOX6 chemotherapy * Arm B: PledOx (5 µmol/kg) + mFOLFOX6 chemotherapy * Arm C: Placebo + mFOLFOX6 chemotherapy Before March 2nd., 2020, the Investigational Medicinal Product, (IMP; i.e. PledOx or placebo) was administered by an intravenous infusion on the first day of each chemotherapy (mFOLFOX6) cycle. IMP was not to be administered if mFOLFOX6 was not given to the patient. If a patient later discontinues oxaliplatin, treatment with 5-FU/folinate may be continued. The addition of an appropriate biologic therapy (bevacizumab, panitumumab, cetuximab) will be left to the discretion of the Investigator. As of March 2nd., all patients have to stop IMP but may continue mFOLFOX 6

Conditions

• Colorectal Cancer
• Chemotherapy-induced Peripheral Neuropathy

Interventions

Type	Name	Description
DRUG	Calmangafodipir (2 µmol/kg)	Solution in 20 mL single dose glass vials
DRUG	Calmangafodipir (5 µmol/kg)	Solution in 20 mL single dose glass vials
DRUG	Placebo	Solution in 20 mL single dose glass vials

Timeline

• Start date: 2018-11-07
• Primary completion: 2020-08-31
• Completion: 2020-08-31
• First posted: 2018-08-31
• Last updated: 2021-12-17
• Results posted: 2021-12-17

Locations

98 sites across 13 countries: United States, Belgium, Czechia, France, Germany, Hong Kong, Hungary, Italy, Japan, South Korea, Spain, Taiwan, United Kingdom

Regulatory

• FDA-regulated drug study