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-DE
• Lead Sponsor: PledPharma AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-04-04
• Last Update Posted: 19 October 2020

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, 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 women of child-bearing potential.
15. For men and females of childbearing potential, 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.
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 140
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 140

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 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.

Study & Design

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