Etude : POLAR-A / PP06489

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Type d'étude
Présentation de l'étude
Acronyme : POLAR-A

Nom : PP06489

Traitement : Adjuvant / Métastasique ou localement avancé

Type d'étude : Hors ciblage moléculaire

Dernière MÀJ : 10/07/2019
CIM10 - Localisation(s)
Informations principales
Titre : 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

Spécialité : Organes digestifs
Localisation : C18 - Tumeur maligne du côlon

Spécialité : Organes digestifs
Localisation : C20 - Tumeur maligne du rectum
Informations complémentaires
Schéma : Main objective of the trial
To compare PledOx (5 µmol/kg) vs placebo with respect to the proportion of patients with moderate or severe chronic CIPN

Secondary objectives of the trial
To compare PledOx vs placebo:

• The proportion of patients with mild, moderate or severe chronic CIPN
• The sensitivity to touching cold items
• The cumulative dose of oxaliplatin during chemotherapy
• The vibration sensitivity on the lateral malleolus
• The worst pain in hands or feet
• The functional impairment (in the non-dominant hand)
• The sustained efficacy on prevention of CIPN during long-term follow-up

• Safety and tolerability

• Chronic CIPN by supporting analysis using the full FACT/GOG NTX-13
• The cumulative dose of 5-FU during chemotherapy
• For both oxaliplatin and 5-FU: Dose intensity, number of cycles, dose reductions, reason(s) for dose reductions, patients with dose delays, and length of dose delays
• Quality of Life/health status
• The functional impairment (in the non-dominant hand) during long-term follow-up
• The worst pain in hands or feet during long-term follow-up.
• Health economic impact

Phase : III

Stade : II à III

Critères d'inclusion
Critères de non-inclusion
Critères d'inclusion et de non-inclusion
Critères d'inclusion : 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 not less than 28 days and generally not more than 8-12 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 any clinically observed neurological disorders.
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 Cockroft 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.

Critères de non-inclusion : 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 prior oxaliplatin-based chemotherapy <1 year before the randomization.
5. Any evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory, cardiac, unresolved bowel obstruction, hepatic or renal disease).
6. Chronic infection or uncontrolled serious illness causing immunodeficiency.
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.
Informations relatives au promoteur
Promoteur :
PledPharma AB
Type de sponsor : Industriel

Coordonnateur :
Centre investigateur
Informations relatives aux investigateurs
Centre investigateur :
Centre Oscar Lambret - 3 Rue Frédéric Combemale - 59000 LILLE

Investigateur :
Docteur Aurélien CARNOT

Unité Intégrée de Recherche Clinique

Ouverture de l'essai : OUVERT

MAJ : 10/07/2019