Preventive Treatment of OxaLiplatin Induced peripherAl neuRopathy in Adjuvant Colorectal Cancer

• Status: Completed
• Trial end date: 2020-08-31
• Target enrollment: 0
• Participant gender: All

Summary

This study is to evaluate PledOx for prevention of chronic chemotherapy induced peripheral neuropathy induced by oxaliplatin in patients with Stage III or high-risk Stage II colorectal cancer (CRC).

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Egetis Therapeutics; PledPharma AB
• Collaborator: Solasia Pharma K.K.
• Treatments: Oxaliplatin

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 within 12 weeks prior to randomization

5. The patient has a postsurgical carcinoembryonic antigen (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 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. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

9. Adequate hematological parameters: hemoglobin ≥100 g/L, absolute neutrophil count ≥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); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 x ULN.

12. Baseline blood manganese (Mn) level <2.0 x ULN.

13. For patients with a history of diabetes mellitus, HbA1c ≤7%.

14. Negative pregnancy test for women of child-bearing potential (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:

1. Any evidence of metastatic disease.

2. Any unresolved toxicity by National Cancer Institute-Common Terminology Criteria for Adverse Events Version (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 evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory, cardiac, unresolved bowel obstruction, hepatic or renal disease).

5. Chronic infection or uncontrolled serious illness causing immunodeficiency. Patients with known history of chronic hepatitis B can be enrolled if they are asymptomatic and an acute and active HBV infection can be excluded.

6. Any history of seizures.

7. A surgical incision that is not 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.