Preventive Treatment of OxaLiplatin Induced peripherAl neuRopathy in Adjuvant Colorectal Cancer

NCT ID: NCT04034355

Last Updated: 2022-01-26

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 301 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-07
• Study Completion Date: 2020-08-31

Brief 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).

Detailed Description

This is a Phase 3, multicenter, double-blind, placebo-controlled study with PledOx for prevention of chronic CIPN induced by oxaliplatin in patients with Stage III or high-risk Stage II colorectal cancer (CRC).

Patients with CRC, who are indicated for adjuvant modified FOLFOX6 (mFOLFOX6) chemotherapy for up to 6 months, will be randomized in a 1:1 ratio to 1 of 2 treatment arms:

• Arm A: PledOx (5 µmol/kg) + mFOLFOX6 chemotherapy
• Arm B: Placebo + mFOLFOX6 chemotherapy

Before March 2nd., 2020, the investigational medicinal product (IMP; i.e. PledOx or placebo) was administered by an intravenous (i.v.) infusion on the first day of each chemotherapy 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 and IMP may be continued.

As of March 2nd., all patients have to stop IMP but may continue mFOLFOX6.

Conditions

Colorectal Cancer; Chemotherapy-induced Peripheral Neuropathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

PledOx (5 µmol/kg)

Calmangafodipir 5 µmol/kg

Group Type: EXPERIMENTAL

Calmangafodipir (5 µmol/kg)

Intervention Type: DRUG

PledOx will be given to patients as an i.v. infusion, on top of mFOLFOX6 chemotherapy. PledOx is a solution in 20 mL single dose glass vials.

Placebo

0.9% sodium chloride in 20 mL vials

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo will be administered via the same route as PledOx (i.v. infusion). Placebo is a solution in 20 mL single dose glass vials.

Interventions

Calmangafodipir (5 µmol/kg)

PledOx will be given to patients as an i.v. infusion, on top of mFOLFOX6 chemotherapy. PledOx is a solution in 20 mL single dose glass vials.

Intervention Type: DRUG

Placebo

Placebo will be administered via the same route as PledOx (i.v. infusion). Placebo is a solution in 20 mL single dose glass vials.

Intervention Type: OTHER

Other Intervention Names

PledOx

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Solasia Pharma K.K.

INDUSTRY

Sponsor Role: collaborator

Egetis Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stefan Carlsson, MD

Role: STUDY_DIRECTOR

Chief Medical Officer

Locations

Onze-Lieve-Vrouwziekenuis Aalst

Aalst, , Belgium

Imelda GI Clinical Research Center

Bonheiden, , Belgium

Cliniques Universitaires St-Luc

Brussels, , Belgium

UZ Gent

Ghent, , Belgium

CHU Liège

Liège, , Belgium

AZ Sint Maarten

Mechelen, , Belgium

AZ Delta

Roeselare, , Belgium

CHU UCL Namur - Site Godinne

Yvoir, , Belgium

Nemocnice Benesov

Benešov, , Czechia

Nemocnice Horovice

Hořovice, , Czechia

Nemocnice Na Pleši

Nová Ves Pod Plesi, , Czechia

General University Hospital

Prague, , Czechia

Onkologická Klinika 1. Lf Uk A Tn

Prague, , Czechia

CHRU de Brest - Hôpital Morvan

Brest, , France

Clinique Pasteur-Lanroze

Brest, , France

Centre Hospitalier Départemental de Vendée - Unité de recherche clinique

La Roche-sur-Yon, , France

Centre Oscar Lambret

Lille, , France

Hôpital Edouard Herriot - HCL

Lyon, , France

Hôpital Nord Franche-Comté Site du Mittan

Montbéliard, , France

CHU Nice L'Archet 2

Nice, , France

Clinique Ste Anne

Strasbourg, , France

Hopitaux Universitaires de Strasbourg

Strasbourg, , France

Hämatolgisch-onkologische Praxis Augsburg

Augsburg, , Germany

Onkozentrum Dresden

Dresden, , Germany

Universitätsklinikum Carl Gustav Carus

Dresden, , Germany

Onkodok GmbH / Onkologische Schwerpunktpraxis

Gütersloh, , Germany

Klinikum Neuperlach

München, , Germany

Oncologia Istituti Ospitalieri

Cremona, , Italy

Irccs Irst

Meldola - FC, , Italy

Hospital San Gerardo

Monza, , Italy

Istituto Nazionale Tumori

Napoli, , Italy

IRCCS Policlinico San Matteo

Pavia, , Italy

Ospedale degli infermi

Ponderano, , Italy

IRCCS azienda Ospedaliera S Maria Nuova

Reggio Emilia, , Italy

Casa Sollievo della Sofferenza

San Giovanni Rotondo, , Italy

Fukuoka University Hospital

Fukuoka, , Japan

Kyushu University Hospital

Fukuoka, , Japan

St. Marianna University School of Medicine Hospital

Kawasaki, , Japan

Aichi Cancer Center Hospital

Nagoya, , Japan

National Hospital Organization Osaka National Hospital

Osaka, , Japan

Osaka International Cancer Institute

Osaka, , Japan

Osaka University Hospital

Osaka, , Japan

Sapporo Medical University Hospital

Sapporo, , Japan

Shizuoka Cancer Center

Shizuoka, , Japan

The Cancer Institute Hospital of JFCR

Tokyo, , Japan

Fujita Health University Hospital

Toyoake, , Japan

Hallym University Sacred Heart Hospital

Anyang-si, , South Korea

Dong-A University Hospital

Busan, , South Korea

Chonnam National University Hwasun Hospital

Gwangju, , South Korea

Seoul National University Bundang Hospital

Seongnam-si, , South Korea

Korea University Guro Hospital

Seoul, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Granvia de L´Hospitalet 199-203

Barcelona, , Spain

Hospital de La Santa Creu I Sant Pau

Barcelona, , Spain

Vall d'hebron university hospital

Barcelona, , Spain

Centro Integral Oncologico

Madrid, , Spain

H.G.U.Gregorio Marañón

Madrid, , Spain

Hospital Universitario Puerta de Hierro

Majadahonda, , Spain

Hospital Univ Virgen Macarena

Seville, , Spain

Hospital Quironsalud Valencia

Valencia, , Spain

KMUH: Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, , Taiwan

Mid Essex Hospital Services NHS Trust - Broomfield Hospital

Chelmsford, , United Kingdom

North Tyneside General Hospital

North Shields, , United Kingdom

Mount Vernon Cancer Centr

Northwood, , United Kingdom

The Royal Marsden Hospital (Surrey)

Sutton, , United Kingdom

Countries

Belgium; Czechia; France; Germany; Italy; Japan; South Korea; Spain; Taiwan; United Kingdom

References

Pfeiffer P, Lustberg M, Nasstrom J, Carlsson S, Persson A, Nagahama F, Cavaletti G, Glimelius B, Muro K. Calmangafodipir for Prevention of Oxaliplatin-Induced Peripheral Neuropathy: Two Placebo-Controlled, Randomized Phase 3 Studies (POLAR-A/POLAR-M). JNCI Cancer Spectr. 2022 Nov 1;6(6):pkac075. doi: 10.1093/jncics/pkac075.

Reference Type: DERIVED

PMID: 36308441 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2017-004707-43

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

PP06489

Identifier Type: -

Identifier Source: org_study_id