Preventive Treatment of OxaLiplatin Induced peripherAl neuRopathy in Adjuvant Colorectal Cancer

NCT04034355 | Terminated Phase 3 Results DMC

• 2 other identifiers: PP064892017-004707-43
• Study Type: interventional
• Target: 301
• Locations: 10 countries
• Sites: 65

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).

Conditions

Colorectal Cancer; Chemotherapy-induced Peripheral Neuropathy

Keywords

colorectal cancer; cancer; peripheral neuropathy; neuropathy

Outcome Measures

Primary Outcomes (1)

• Moderate or Severe Chronic Chemotherapy Induced Peripheral Neuropathy (CIPN)

  Percentage of patients (with moderate or severe chronic CIPN) scoring 3 or 4 in at least 1 of the first 4 items of the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity-13-item subscale (FACT/GOG-NTX-13; i.e., FACT/GOG-NTX-4) 9 months after the first dose of IMP (i.e. PledOx or placebo administered on Day 1, Cycle 1 of mFOLFOX6 chemotherapy). The FACT/GOG-13 questionnaire includes 13 items that measure the severity and impact of symptoms of neurotoxicity over the past 7 days. Patients rate each item as 0 ("not at all"), 1 (" a little bit"), 2 ("somewhat"), 3 ("quite a bit") or 4 ("very much"). These 13 items are summed to create a total score, ranging from 0 to 52, with a higher score representing a worse outcome. The FACT/GOG-NTX-4 is a 4 item subscale targeting numbness, tingling or discomfort in hands and/or feet.

  9 months

Secondary Outcomes (7)

• Mild, Moderate or Severe Chronic Chemotherapy Induced Peripheral Neuropathy

  9 months

• Sensitivity to Touching Cold Items

  Baseline and 8 weeks

• Cumulative Dose of Oxaliplatin During Chemotherapy

  9 months

• Vibration Sensitivity on the Lateral Malleolus

  Baseline and 9 months

• Worst Pain in Hands or Feet

  Baseline and 9 months

Study Arms (2)

PledOx (5 µmol/kg)

EXPERIMENTAL

Calmangafodipir 5 µmol/kg

Drug: Calmangafodipir (5 µmol/kg)

Placebo

PLACEBO COMPARATOR

0.9% sodium chloride in 20 mL vials

Other: Placebo

Interventions

Calmangafodipir (5 µmol/kg) 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.

Also known as: PledOx

PledOx (5 µmol/kg)

Placebo 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.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent form before any study related assessments and willing to follow all study procedures.
• Male or female aged ≥18 years.
• 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).
• The patient has undergone curative (R0) surgical resection performed within 12 weeks prior to randomization
• 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).
• No prior anti-cancer therapy for CRC except radiotherapy or concomitant chemo-radiotherapy using a fluoropyrimidine alone for locoregional rectal cancer.
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate hematological parameters: hemoglobin ≥100 g/L, absolute neutrophil count ≥1.5 x 109 /L, platelets ≥100 x 109 /L.
• Adequate renal function: creatinine clearance \>50 cc/min using the Cockcroft and Gault formula or measured.
• 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.
• Baseline blood manganese (Mn) level \<2.0 x ULN.
• For patients with a history of diabetes mellitus, HbA1c ≤7%.
• Negative pregnancy test for women of child-bearing potential (WOCBP).
• 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.

You may not qualify if:

• Any evidence of metastatic disease.
• 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.
• Any grade of neuropathy from any cause.
• Any evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory, cardiac, unresolved bowel obstruction, hepatic or renal disease).
• 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.
• Any history of seizures.
• A surgical incision that is not healed.
• 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.
• 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.
• Known dihydropyrimidine dehydrogenase deficiency.
• 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).
• Major psychiatric disorder (major depression, psychosis), alcohol and/or drug abuse.
• Patients with a history of second or third degree atrioventricular block or a family heredity.
• A history of a genetic or familial neuropathy.
• Treatment with any investigational drug within 30 days prior to randomization.

Sponsors & Collaborators

• Egetis Therapeutics: lead
• Solasia Pharma K.K.: collaborator

Study Sites (65)

Onze-Lieve-Vrouwziekenuis Aalst

Aalst, Belgium

Location

Imelda GI Clinical Research Center

Bonheiden, Belgium

Location

Cliniques Universitaires St-Luc

Brussels, Belgium

Location

UZ Gent

Ghent, Belgium

Location

CHU Liège

Liège, Belgium

Location

AZ Sint Maarten

Mechelen, Belgium

Location

AZ Delta

Roeselare, Belgium

Location

CHU UCL Namur - Site Godinne

Yvoir, Belgium

Location

Nemocnice Benesov

Benešov, Czechia

Location

Nemocnice Horovice

Hořovice, Czechia

Location

Nemocnice Na Pleši

Nová Ves Pod Plesi, Czechia

Location

General University Hospital

Prague, Czechia

Location

Onkologická Klinika 1. Lf Uk A Tn

Prague, Czechia

Location

CHRU de Brest - Hôpital Morvan

Brest, France

Location

Clinique Pasteur-Lanroze

Brest, France

Location

Centre Hospitalier Départemental de Vendée - Unité de recherche clinique

La Roche-sur-Yon, France

Location

Centre Oscar Lambret

Lille, France

Location

Hôpital Edouard Herriot - HCL

Lyon, France

Location

Hôpital Nord Franche-Comté Site du Mittan

Montbéliard, France

Location

CHU Nice L'Archet 2

Nice, France

Location

Clinique Ste Anne

Strasbourg, France

Location

Hopitaux Universitaires de Strasbourg

Strasbourg, France

Location

Hämatolgisch-onkologische Praxis Augsburg

Augsburg, Germany

Location

Onkozentrum Dresden

Dresden, Germany

Location

Universitätsklinikum Carl Gustav Carus

Dresden, Germany

Location

Onkodok GmbH / Onkologische Schwerpunktpraxis

Gütersloh, Germany

Location

Klinikum Neuperlach

München, Germany

Location

Oncologia Istituti Ospitalieri

Cremona, Italy

Location

Irccs Irst

Meldola - FC, Italy

Location

Hospital San Gerardo

Monza, Italy

Location

Istituto Nazionale Tumori

Napoli, Italy

Location

IRCCS Policlinico San Matteo

Pavia, Italy

Location

Ospedale degli infermi

Ponderano, Italy

Location

IRCCS azienda Ospedaliera S Maria Nuova

Reggio Emilia, Italy

Location

Casa Sollievo della Sofferenza

San Giovanni Rotondo, Italy

Location

Fukuoka University Hospital

Fukuoka, Japan

Location

Kyushu University Hospital

Fukuoka, Japan

Location

St. Marianna University School of Medicine Hospital

Kawasaki, Japan

Location

Aichi Cancer Center Hospital

Nagoya, Japan

Location

National Hospital Organization Osaka National Hospital

Osaka, Japan

Location

Osaka International Cancer Institute

Osaka, Japan

Location

Osaka University Hospital

Osaka, Japan

Location

Sapporo Medical University Hospital

Sapporo, Japan

Location

Shizuoka Cancer Center

Shizuoka, Japan

Location

The Cancer Institute Hospital of JFCR

Tokyo, Japan

Location

Fujita Health University Hospital

Toyoake, Japan

Location

Hallym University Sacred Heart Hospital

Anyang-si, South Korea

Location

Dong-A University Hospital

Busan, South Korea

Location

Chonnam National University Hwasun Hospital

Gwangju, South Korea

Location

Seoul National University Bundang Hospital

Seongnam-si, South Korea

Location

Korea University Guro Hospital

Seoul, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

Granvia de L´Hospitalet 199-203

Barcelona, Spain

Location

Hospital de La Santa Creu I Sant Pau

Barcelona, Spain

Location

Vall d'hebron university hospital

Barcelona, Spain

Location

Centro Integral Oncologico

Madrid, Spain

Location

H.G.U.Gregorio Marañón

Madrid, Spain

Location

Hospital Universitario Puerta de Hierro

Majadahonda, Spain

Location

Hospital Univ Virgen Macarena

Seville, Spain

Location

Hospital Quironsalud Valencia

Valencia, Spain

Location

KMUH: Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, Taiwan

Location

Mid Essex Hospital Services NHS Trust - Broomfield Hospital

Chelmsford, United Kingdom

Location

North Tyneside General Hospital

North Shields, United Kingdom

Location

Mount Vernon Cancer Centr

Northwood, United Kingdom

Location

The Royal Marsden Hospital (Surrey)

Sutton, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 36308441 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasms; Peripheral Nervous System Diseases

Interventions

N,N'-bis(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neuromuscular Diseases; Nervous System Diseases

Results Point of Contact

• Title: Kristina Sjoblom Nygren
• Organization: Egetis Therapeutics AB

kristina.sjoblom@egetis.com

+46 732344698

Study Officials

• Stefan Carlsson, MD

  Chief Medical Officer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double-blind, placebo-controlled
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Patients with colorectal cancer (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

Study Record Dates

• First Submitted: May 14, 2019
• First Posted: July 26, 2019
• Study Start: January 7, 2019
• Primary Completion: August 31, 2020
• Study Completion: August 31, 2020
• Last Updated: January 26, 2022
• Results First Posted: January 26, 2022

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

GB (4); JP (11); KR (6); CZ (5); IT (8); ES (8); TW (1); BE (8); FR (9); DE (5)