A Phase 3, double-blind, multicenter, placebo-controlled study of a new drug, PledOx used on top of standard therapy to prevent damages to nerves of the peripheral nervous system, induced by chemotherapy, in the adjuvant treatment of patients with Stage III or high-risk Stage II cancer of the large intestine.

Phase 1

• Conditions: Chemotherapy induced peripheral neuropathy; MedDRA version: 20.1Level: LLTClassification code 10079545Term: Chemotherapy induced peripheral neuropathySystem Organ Class: 100000004852; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-004707-43-IT
• Lead Sponsor: PLEDPHARMA AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-01-29
• Last Update Posted: 5 April 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 280

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 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 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, 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 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 (AST and ALT =5 x ULN in case of liver metastases).
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 females of child-bearing potential.
15. For men and females of childbearing potential, use of adequate contraception (oral contraceptives, intrauterine device or barrier method of contraception in conjunction with spermicidal jelly or surgically sterile) while on study drug and for at least 6 months after completion of study therapy.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100

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 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 seizure
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.
Please refer to the synospis/protocl

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified