Preventive Treatment of Oxaliplatin Induced Peripheral Neuropathy in Metastatic Colorectal Cancer (POLAR-M)

NCT03654729 | Terminated Phase 3 Results DMC FDA Drug

• 1 other identifier: PP06490
• Study Type: interventional
• Target: 291
• Locations: 13 countries
• Sites: 98

Brief Summary

This study evaluates the investigational drug PledOx in the prevention of chronic chemotherapy induced peripheral neuropathy (CIPN) induced by the drug oxaliplatin.

Conditions

Colorectal Cancer; Chemotherapy-induced Peripheral Neuropathy

Keywords

Metastatic; Colorectal; Cancer; Metastatic Colorectal Cancer; Oxaliplatin induced CIPN; CIPN; Oxaliplatin

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 (9)

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

  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 (3)

PledOx (2 µmol/kg)

EXPERIMENTAL

Calmangafodipir (2 µmol/kg) on day 1 every two weeks to patients as an intravenous infusion, combined with mFOLFOX6 chemotherapy.

Drug: Calmangafodipir (2 µmol/kg)

PledOx (5 µmol/kg)

EXPERIMENTAL

Calmangafodipir (5 µmol/kg) on day 1 every two weeks to patients as an intravenous infusion, combined with mFOLFOX6 chemotherapy.

Drug: Calmangafodipir (5 µmol/kg)

Placebo

PLACEBO COMPARATOR

Placebo will be given to patients as an intravenous infusion, on top of mFOLFOX6 chemotherapy.

Drug: Placebo

Interventions

Calmangafodipir (2 µmol/kg) DRUG

Solution in 20 mL single dose glass vials

Also known as: PledOx

PledOx (2 µmol/kg)

Calmangafodipir (5 µmol/kg) DRUG

Solution in 20 mL single dose glass vials

Also known as: PledOx

PledOx (5 µmol/kg)

Placebo DRUG

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.
• Non-resectable metastatic (stage IV) CRC, pathologically confirmed adenocarcinoma of the colon or rectum.
• No prior chemotherapy (within the previous 12 months) and/or biologic/targeted therapy for mCRC.
• Measurable disease according to RECIST 1.1.
• Patient indicated for at least 3 months of oxaliplatin-based chemotherapy (without any pre-planned treatment breaks) and without any clinically observed neurological disorders.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate hematological parameters: hemoglobin \>=100 g/L, absolute neutrophil count (ANC) \>=1.5 x 10\^9 /L, platelets \>=100 x 10\^9 /L.
• Adequate renal function: creatinine clearance \>50 cc/min using the Cockroft and Gault formula or measured.
• Adequate hepatic function: total bilirubin \<=1.5 times the upper limit of normal (ULN) (except in the case of known Gilbert's syndrome); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<=3 times ULN (AST and ALT \<=5 times ULN in case of liver metastases).
• Baseline blood manganese (Mn) level \<2.0 times ULN.
• For patients with a history of diabetes mellitus, HbA1c \<=7%.
• Negative pregnancy test for females of child-bearing potential.
• 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.

You may not qualify if:

• Any unresolved toxicity by Common Terminology Criteria for Adverse Events Version (CTCAE v4.03) \> 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.
• Any history of seizures.
• A surgical incision that is not healed.
• Significant hemorrhage (\>30 mL/bleeding episode in previous 3 months), hemoptysis (\>5 mL fresh blood in previous 4 weeks) or thrombotic event (including transient ischemic attack) in the previous 12 months if the patient is expected to receive anti-VEGF/VEGFR therapy.
• Known hypersensitivity to any of the components of mFOLFOX6 and, if applicable, biological 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 (98)

California Cancer Associates

Fresno, California, 93720, United States

Location

Mid Florida Hematology and Oncology Center

Orange City, Florida, 32763, United States

Location

Cancer Center of Kansas

Wichita, Kansas, 67214, United States

Location

Willis-Knighton Cancer Center

Shreveport, Louisiana, 71103, United States

Location

Mercy Clinic - Cancer & Hematology

Springfield, Missouri, 65804, United States

Location

Mercy Clinic Oncology and Hematology

St Louis, Missouri, 63141, United States

Location

CHI St Francis Cancer Treatment Center

Grand Island, Nebraska, 68803, United States

Location

Hunterdon Hematology Oncology

Flemington, New Jersey, 08822, United States

Location

Monter Cancer Center

Lake Success, New York, 11042, United States

Location

Montefiore Medical Research

The Bronx, New York, 10461, United States

Location

Scott & White Vasicek Cancer Treatment Center

Temple, Texas, 76508, United States

Location

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 Pleší, Czechia

Location

General University Hospital

Prague, Czechia

Location

Hospital Na Bulovce

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

Institut de Cancérologie de l'Ouest

Nantes, France

Location

Hopital l'Archet, CHU de Nice

Nice, France

Location

Hôpital Robert Debré

Reims, France

Location

Centre Hospitalier Privé Saint-Grégoire

Saint-Grégoire, 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

Agaplesion Markus Krankenhaus

Frankfurt, Germany

Location

Onkodok GmbH

Gütersloh, Germany

Location

Klinikum Neuperlach

München, Germany

Location

Queen Mary Hospital

Hong Kong, Hong Kong

Location

Országos Onkológiai Intézet

Budapest, Hungary

Location

Semmelweis Egyetem

Budapest, Hungary

Location

Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Oktatókórház

Miskolc, Hungary

Location

Tolna Megyei Balassa Janos Korhaz

Szekszárd, Hungary

Location

Jász-Nagykun-Szolnok Megyei Hetényi Géza Kórház-Rendelőintézet

Szolnok, Hungary

Location

IRCCS Candiolo

Candiolo, Italy

Location

Oncologia Istituti Ospitalieri

Cremona, Italy

Location

Irccs Irst

Meldola - FC, Italy

Location

Azienda Ospedaliero - Universitaria di Modena Policlinico

Modena, 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

Ospedale S. Maria delle Croci - Ravenna

Ravenna, Italy

Location

IRCCS azienda Ospedaliera S Maria Nuova

Reggio Emilia, Italy

Location

San Camillo Forlanini Hospital

Rome, Italy

Location

Casa Sollievo della Sofferenza

San Giovanni Rotondo, Italy

Location

Osaka International Cancer Institute

Osaka-shi, Osaka, Osaka, 541-8567, Japan

Location

Fujita Health University Hospital

Aichi, 470-1192, Japan

Location

Kyushu University Hospital

Fukuoka-shi, Fukuoka, 812-8582, Japan

Location

Fukuoka University Hospital

Fukuoka-shi, Fukuoka, 814-0133, Japan

Location

Kansai Rosai Hospital

Hyōgo, Japan

Location

St. Marianna University School of Medicine Hospital

Kanagawa, 216-8511, Japan

Location

Aichi Cancer Center Hospital

Nagoya-shi, Aichi, 464-8681, Japan

Location

Osaka University Hospital

Osaka, 565-0871, Japan

Location

National Hospital Organization Osaka National Hospital

Osaka-shi, Osaka, 540-0006, Japan

Location

Sapporo Medical University Hospital

Sapporo-shi, Hokkaido, 065-0033, Japan

Location

Shizuoka Cancer Center

Shizuoka, 411-8777, Japan

Location

The Cancer Institute Hospital Of JFCR

Tokyo, 135-8550, 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

Hospital de La Santa Creu I Sant Pau

Barcelona, Spain

Location

L´Hospitalet de Llobregat (Barcelona)

Barcelona, Spain

Location

Vall d'hebron university hospital

Barcelona, Spain

Location

Complejo Hospitalario de Jaén

Jaén, Spain

Location

Centro Integral Oncologico Clara Campal

Madrid, Spain

Location

H.G.U.Gregorio Marañón

Madrid, Spain

Location

Hospital Universitario La Paz

Madrid, Spain

Location

Hospital Universitario Puerta de Hierro

Majadahonda, Spain

Location

Hospital Universitario Virgen Macarena

Seville, Spain

Location

Hospital Quironsalud Valencia

Valencia, Spain

Location

Hospital Miguel Servet

Zaragoza, Spain

Location

KMUH: Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, Taiwan

Location

CMMC: Chi Mei Medical Center

Tainan, Taiwan

Location

NCKUH: National Cheng Kung University Hospital

Tainan, Taiwan

Location

Royal Marsden Hospital

London, SW3 6JJ, United Kingdom

Location

North Tyneside General Hospital

North Shields, NE29 8NH, United Kingdom

Location

Mount Vernon Cancer Centre

Northwood, HA6 2RN, United Kingdom

Location

The Royal Marsden Hospital (Surrey)

Sutton, SM2 5PT, United Kingdom

Location

York Teaching Hospital

York, YO61 8HE, 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; Neoplasm Metastasis; Neoplasms

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; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

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

kristina.sjoblom@egetis.com

+46732344698

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
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a Phase 3, multicenter, double-blind, placebo-controlled study to establish the efficacious dose of PledOx in prevention of chronic chemotherapy induced peripheral neuropathy (CIPN) induced by oxaliplatin. Patients with metastatic colorectal cancer (mCRC), who are indicated for first-line modified FOLFOX6 (mFOLFOX6) chemotherapy for at least 3 months, without any pre-planned treatment breaks, will be randomized in a 1:1:1 ratio, stratified by region (Asia, non-Asia) and PK sub-study (yes, no) to one of three treatment arms: * Arm A: PledOx (2 µmol/kg) + mFOLFOX6 chemotherapy * Arm B: PledOx (5 µmol/kg) + m * Arm C: Placebo + mFOLFOX6 chemotherapy

Study Record Dates

• First Submitted: August 29, 2018
• First Posted: August 31, 2018
• Study Start: November 7, 2018
• Primary Completion: August 31, 2020
• Study Completion: August 31, 2020
• Last Updated: December 17, 2021
• Results First Posted: December 17, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

DE (6); US (11); CZ (6); KR (6); ES (11); JP (12); IT (12); FR (12); GB (5); TW (3); HU (5); HK (1); BE (8)