Clinical Trials List
Protocol NumberPP06490
NCT Number(ClinicalTrials.gov Identfier)NCT03654729
2019-03-01 - 2022-12-31
Phase III
Terminated3
ICD-10G62.0
Drug-induced polyneuropathy
ICD-10C18
Malignant neoplasm of colon
ICD-9357.6
Polyneuropathy due to drugs
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 patients with first-line metastatic colorectal cancer
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Trial Applicant
COVANCE TAIWAN SERVICES LIMITED
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Sponsor
PledPharma AB & Solasia Pharma K.K(Co-sponsor in Asia)
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 曹朝榮 Division of Hematology & Oncology
- 曹朝榮, 陳昭勳, 林建良,陳尚文, 陳彥勳, 蕭聖諺 Division of Hematology & Oncology
- 黃文聰 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- Po-Wen Lin Division of Colorectal Surgery
- Peng-Chan Lin Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Co-Principal Investigator
- 蔡祥麟 Division of Colorectal Surgery
- Wei-Chih Su Division of Colorectal Surgery
- 黃敬文 Division of Colorectal Surgery
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Condition/Disease
Prevent chemotherapy-induced peripheral neuropathy (CIPN)
Objectives
Prevent chemotherapy-induced peripheral neuropathy (CIPN)
Test Drug
PledOx
Active Ingredient
calmangafodipir
Dosage Form
IV injection
Dosage
50 mM in 20 ml vial
Endpoints
• 9 months after the first dose of IMP (ie, PledOx or placebo administered on the first day of the first cycle of mFOLFOX6 chemotherapy), for numbness, tingling or discomfort in the hands and/or feet, in FACT/GOG-NTX -13 The proportion of patients with at least one of the first 4 items (ie FACT/GOG-NTX-4) rated as 3 or 4 (moderate or severe chronic CIPN).
Inclution Criteria
1. Sign an informed consent form before conducting any relevant assessments and are willing to abide by all research procedures.
2. Male or female who is over 18 years old.
3. Unresectable metastatic (stage 4) CRC, pathologically confirmed as colon or rectal adenocarcinoma.
4. Did not receive systemic chemotherapy and/or metastatic CRC biologics/targeted course of treatment beforehand.
5. According to RECIST version 1.1, there is a measurable tumor.
6. Patients who are recommended to receive Oxaliplatin-type chemotherapy for at least 3 months (without any planned treatment interruption), and have no pathological findings in neurological examinations based on local procedures before Oxaliplatin treatment.
7. The daily physical status of the United States East Coast Cancer Clinical Research Cooperative (ECOG) is 0 or 1 points.
8. Sufficient blood value: hemoglobin ≥100 g/L, absolute neutrophil (ANC) ≥1.5 x 109/L, platelet ≥100 x 109/L.
9. Adequate renal function: Creatinine clearance rate >50 cc/min, estimated using Cockcroft-Gault formula or directly measured.
10. Sufficient liver function: total bilirubin ≤1.5 times upper limit of normal (ULN) (except for known cases of Gilbert’s syndrome); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 Times ULN (AST and ALT ≤ 5 times ULN in patients with liver metastases).
11. Baseline blood manganese (Mn) value <2.0 times ULN.
12. For patients with a history of diabetes, HbA1c ≤7%.
13. Women of Reproductive Ability (WOCBP) have a negative pregnancy test.
14. For men and WOCBP, implement appropriate contraceptive measures (oral contraceptives, intrauterine contraceptives or barrier methods with spermicide or surgical sterilization) at least 6 months after using the trial drug and completing the study therapy.
2. Male or female who is over 18 years old.
3. Unresectable metastatic (stage 4) CRC, pathologically confirmed as colon or rectal adenocarcinoma.
4. Did not receive systemic chemotherapy and/or metastatic CRC biologics/targeted course of treatment beforehand.
5. According to RECIST version 1.1, there is a measurable tumor.
6. Patients who are recommended to receive Oxaliplatin-type chemotherapy for at least 3 months (without any planned treatment interruption), and have no pathological findings in neurological examinations based on local procedures before Oxaliplatin treatment.
7. The daily physical status of the United States East Coast Cancer Clinical Research Cooperative (ECOG) is 0 or 1 points.
8. Sufficient blood value: hemoglobin ≥100 g/L, absolute neutrophil (ANC) ≥1.5 x 109/L, platelet ≥100 x 109/L.
9. Adequate renal function: Creatinine clearance rate >50 cc/min, estimated using Cockcroft-Gault formula or directly measured.
10. Sufficient liver function: total bilirubin ≤1.5 times upper limit of normal (ULN) (except for known cases of Gilbert’s syndrome); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 Times ULN (AST and ALT ≤ 5 times ULN in patients with liver metastases).
11. Baseline blood manganese (Mn) value <2.0 times ULN.
12. For patients with a history of diabetes, HbA1c ≤7%.
13. Women of Reproductive Ability (WOCBP) have a negative pregnancy test.
14. For men and WOCBP, implement appropriate contraceptive measures (oral contraceptives, intrauterine contraceptives or barrier methods with spermicide or surgical sterilization) at least 6 months after using the trial drug and completing the study therapy.
Exclusion Criteria
1. According to the National Cancer Institute Common Adverse Events Evaluation Standard (NCI-CTCAE 4.03 version), any toxicity> level 1 caused by any previous anti-cancer therapy (including radiotherapy) has not been relieved, except for baldness.
2. Any level of neuropathy caused by any cause.
3. Any evidence of severe or uncontrolled systemic disease (such as unstable or compensated breathing, heart, unresolved intestinal obstruction, liver or kidney disease).
4. Chronic infection or uncontrolled serious illness that causes immunodeficiency. If the patient is known to have a history of chronic hepatitis B, asymptomatic patients can be included, and those with acute and active hepatitis B virus infection will be excluded.
5. Any history of epilepsy
6. The surgical incision has not healed yet.
7. If the patient is expected to receive anti-vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor (VEGFR) therapy, severe bleeding has occurred in the past 12 months (each bleeding event in the past 3 months> 30 ml) , Hemoptysis (>5 ml of fresh blood in the past 4 weeks) or thrombotic events (including transient cerebral ischemia).
8. Those who are allergic to any mFOLFOX6 ingredients and (if applicable) biological therapies used with chemotherapy regimens or any excipients of these products.
9. A medical history of other malignancies (except for basal cell carcinoma or squamous cell carcinoma or carcinoma in situ that have received appropriate treatment) within 5 years, unless the patient has not developed such other malignant diseases for at least 2 years.
10. Known dihyyrimidine dehydrogenase deficiency.
11. Pre-existing neurodegenerative diseases (for example: Parkinson’s disease, Alzheimer’s disease, Huntington’s disease) or neuromuscular disorders (for example: multiple sclerosis, amyotrophic lateral sclerosis, pediatric Paralysis, hereditary neuromuscular disease).
12. People with major mental illness (severe depression, mental disorders), alcohol and/or drug abusers.
13. Patients with a history of atrioventricular block or family genetic history of second or third grade atrioventricular block.
14. There is a history of genetic or familial neuropathy.
15. Receive any study drug treatment within 30 days before random assignment.
16. Those who are pregnant, breastfeeding or unwilling to use contraception.
17. According to the opinion of the trial leader, any other conditions that put the patient at unnecessary risk.
18. Have used mangafodipir or calmangafodipir before.
19. Workers who are welders, miners or other occupations (current or former) who may be exposed to high manganese environments.
2. Any level of neuropathy caused by any cause.
3. Any evidence of severe or uncontrolled systemic disease (such as unstable or compensated breathing, heart, unresolved intestinal obstruction, liver or kidney disease).
4. Chronic infection or uncontrolled serious illness that causes immunodeficiency. If the patient is known to have a history of chronic hepatitis B, asymptomatic patients can be included, and those with acute and active hepatitis B virus infection will be excluded.
5. Any history of epilepsy
6. The surgical incision has not healed yet.
7. If the patient is expected to receive anti-vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor (VEGFR) therapy, severe bleeding has occurred in the past 12 months (each bleeding event in the past 3 months> 30 ml) , Hemoptysis (>5 ml of fresh blood in the past 4 weeks) or thrombotic events (including transient cerebral ischemia).
8. Those who are allergic to any mFOLFOX6 ingredients and (if applicable) biological therapies used with chemotherapy regimens or any excipients of these products.
9. A medical history of other malignancies (except for basal cell carcinoma or squamous cell carcinoma or carcinoma in situ that have received appropriate treatment) within 5 years, unless the patient has not developed such other malignant diseases for at least 2 years.
10. Known dihyyrimidine dehydrogenase deficiency.
11. Pre-existing neurodegenerative diseases (for example: Parkinson’s disease, Alzheimer’s disease, Huntington’s disease) or neuromuscular disorders (for example: multiple sclerosis, amyotrophic lateral sclerosis, pediatric Paralysis, hereditary neuromuscular disease).
12. People with major mental illness (severe depression, mental disorders), alcohol and/or drug abusers.
13. Patients with a history of atrioventricular block or family genetic history of second or third grade atrioventricular block.
14. There is a history of genetic or familial neuropathy.
15. Receive any study drug treatment within 30 days before random assignment.
16. Those who are pregnant, breastfeeding or unwilling to use contraception.
17. According to the opinion of the trial leader, any other conditions that put the patient at unnecessary risk.
18. Have used mangafodipir or calmangafodipir before.
19. Workers who are welders, miners or other occupations (current or former) who may be exposed to high manganese environments.
The Estimated Number of Participants
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Taiwan
3 participants
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Global
291 participants
