A Trial of PledOx + FOLFOX6 Compared to Placebo + FOLFOX6 in Patients With Metastatic Colorectal Cancer (PLIANT)
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| ClinicalTrials.gov Identifier: NCT01619423 |
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Recruitment Status :
Completed
First Posted : June 14, 2012
Results First Posted : July 6, 2018
Last Update Posted : July 6, 2018
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The present trial is designed to determine whether pre-treatment with PledOx lowers the frequency and severity of side effects from FOLFOX6 administration in patients with metastatic colorectal cancer.
The efficacy of PledOx will be assessed when added to FOLFOX6 chemotherapy as first line treatment of metastatic colorectal cancer.
This study was performed in multiple parts/phases. Part 1 was an open dose-escalation study with the doses 2, 5 and 10 micromol/kg of calmangafodipir. No study outcomes were planned for this part. In part 2a, participants randomly received either Placebo, 2 or 10 micromol/kg of calmangafodipir. In part 2b, participants randomly received either Placebo, 2 or 5 micromol/kg of calmangafodipir. The overall intent of the study was to compare the effect of antioxidant agent PledOx against placebo in one of three different doses/combinations (2 micromol/kg, 5/10 micromol/kg, 2/5/10 micromol/kg vs. placebo, in the first 8 cycles of FOLFOX6 treatment
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Advanced Metastatic (Stage IV) Colorectal Cancer | Drug: PledOx (2 µmol/kg) Drug: PledOx (5 µmol/kg) Drug: PledOx (10 µmol/kg) Drug: Placebo (0,9% NaCl) | Phase 1 Phase 2 |
Globally, nearly 800 000 colorectal cancers are believed to occur annually. Approximately about half of the patients with colorectal cancer develop metastatic disease. These patients are often offered chemotherapy with the FOLFOX6 regimen (FOL = FOLic acid; F = Fluorouracil (5-FU); OX = OXaliplatin) The use of FOLFOX6 is, however, hampered by a high incidence and severity of adverse reactions.
In the current trial patients will receive the antioxidant agent PledOx in one of two different doses, or placebo, in the first 8 cycles of FOLFOX6 treatment.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 186 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | The study is a three arm study, however, we changed the high dose in the secord part of the study, from 10 micromol/kg (part 2a) to 5 mictomol/kg (part 2b) |
| Masking: | Triple (Participant, Care Provider, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | A Double Blinded Randomised Three Armed Phase II Trial of PledOx in Two Different Doses in Combination With FOLFOX6 Compared to Placebo + FOLFOX6 in Patients With Advanced Metastatic Colorectal (Stage IV) Cancer |
| Study Start Date : | September 2012 |
| Actual Primary Completion Date : | March 2016 |
| Actual Study Completion Date : | December 2016 |
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: FOLFOX6 + PledOx 2 µmol/kg
PledOx active ingredient= Calmangafodipir; FOLFOX6=Combination of FOLinic Acid, 5-Fluorouracil (5-FU), and Oxaliplatin.
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Drug: PledOx (2 µmol/kg)
PledOx is administered intravenously for up to 5 minutes, about 10 min prior to start of FOLFOX6 chemotherapy which will be administered day 1 and 2 every second week for up to 8 cycles.
Other Name: Calmangafodipir |
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Active Comparator: FOLFOX6 + PledOx 5 µmol/kg
PledOx active ingredient= Calmangafodipir; FOLFOX6=Combination of FOLinic Acid, 5-Fluorouracil (5-FU), and Oxaliplatin.
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Drug: PledOx (5 µmol/kg)
PledOx is administered intravenously for up to 5 minutes, about 10 min prior to start of FOLFOX6 chemotherapy which will be administered day 1 and 2 every second week for up to 8 cycles
Other Name: Calmangafodipir |
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Active Comparator: FOLFOX6 + PledOx 10 µmol/kg
PledOx active ingredient= Calmangafodipir; FOLFOX6=Combination of FOLinic Acid, 5-Fluorouracil (5-FU), and Oxaliplatin.
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Drug: PledOx (10 µmol/kg)
PledOx is administered intravenously for up to 5 minutes, about 10 min prior to start of FOLFOX6 chemotherapy which will be administered day 1 and 2 every second week for up to 8 cycles
Other Name: Calmangafodipir |
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Placebo Comparator: FOLFOX6 + 0,9% NaCl
Placebo= 0.9% NaCl; FOLFOX6=Combination of FOLinic Acid, 5-Fluorouracil (5-FU), and Oxaliplatin.
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Drug: Placebo (0,9% NaCl)
Placebo (0,9% NaCl) is administered intravenously for up to 5 minutes, about 10 min prior to start of FOLFOX6 chemotherapy which will be administered day 1 and 2 every second week for up to 8 cycles.
Other Name: Sodium chloride |
- Number of Patients With Neuropathy Grade 2 or Higher (According to the Oxaliplatin Specific Sanofi Scale (OSSS) Criteria Related Paraesthesia/Dysaesthesia) [ Time Frame: Every second week during cycle 1-8, for up to 16 weeks ]Percentage of patients, over cycle 1 to 8, with neuropathy grade 2 or higher (according to the Oxaliplatin Specific Sanofi Scale (OSSS) criteria related paraesthesiae/dysaesthesiae)
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Advanced metastatic colorectal (stage IV) cancer verified by biopsy
- Patients may have received up to three previous treatment lines of chemotherapy, which may include fluoropyrimidine, irinotecan and targeted therapies. The last dose of antitumor drug must be given at least 4 weeks prior to inclusion and all toxicity (except alopecia and fatigue) resolved. Patients may also be chemotherapy-naïve, have received prior adjuvant treatment but no previous treatment with oxaliplatin
- CT-scan or MRI of thorax, abdomen and pelvis; within ≤4 weeks before start of chemotherapy
- Evaluable disease and one measurable site of disease according to RECIST 1.1 criteria (at least 10mm for CT-scan or MRI)
- Neurological examination with no significant pathological findings
- ≥18 years
- WHO performance status 0≤2 and Life expectancy ≥ 3 months
- Adequate haematological function, Hb ≥ 100 g/L, ANC ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L
- Adequate renal and hepatic functions: creatinine clearance >50 cc/min, total bilirubin ≤ 1.5 times ULN, ASAT and ALAT ≤ 3 times ULN (ASAT and ALAT ≤ 5 times ULN in case of liver metastases)
- INR ≤1.5 times ULN, unless receiving therapeutic anticoagulation
- Negative pregnancy test for females of child-producing potential
- Written informed consent given
Exclusion Criteria:
- Tumours other than colorectal adenocarcinomas (within the previous 5 years) except for curatively treated non melanoma skin cancer or in situ carcinoma of the cervix
- Evidence of central nervous system metastases
- Unresolved bowel obstruction or sub-obstruction, uncontrolled Crohn's disease or ulcerative colitis
- History of cardiac disease with a New York Heart Association (NYHA) Class II or greater congestive heart failure, myocardial infarction or unstable angina in the past six (6) months prior to Day 1 of treatment and serious arrhythmias requiring medication for treatment
- Prolonged QTC interval >450 msec
- Known history of stroke or cerebrovascular accident in the past six (6) months
- Severe diarrhoea
- Chronic infection or uncontrolled serious illness causing immunodeficiency
- Any uncontrolled serious illness or medical condition
- Received mangafodipir at any time
- Welders, mine workers or other workers in occupations (current or past) where high manganese exposure is likely
- Pre-existing neurodegenerative disease (Parkinson's, Alzheimer's, Huntington's etc.) or neuromuscular disorder (Multiple sclerosis, Amyotrophic lateral sclerosis, Polio, hereditary neuromuscular disease)
- Major psychiatric disorder (major depression, psychosis)
- Participation in another clinical study with an investigational medicinal product within 1 month prior to inclusion.
- Blood manganese concentration values >18.3 μg/L at screening
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01619423
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| Study Director: | Marie Bengtson | Egetis Therapeutics |
| Responsible Party: | Egetis Therapeutics |
| ClinicalTrials.gov Identifier: | NCT01619423 |
| Other Study ID Numbers: |
PP095, (PLIANT) 2012-001367-76 ( EudraCT Number ) |
| First Posted: | June 14, 2012 Key Record Dates |
| Results First Posted: | July 6, 2018 |
| Last Update Posted: | July 6, 2018 |
| Last Verified: | July 2018 |
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Metastatic colorectal cancer stage IV FOLFOX6 Chemotherapy PledOx Mangafodipir |
Febrile neutropenia Oxidative stress Antioxidant neutropenia neuropathy |
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Colorectal Neoplasms Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Digestive System Diseases Gastrointestinal Diseases Colonic Diseases Intestinal Diseases Rectal Diseases |
Pyridoxal Phosphate Edetic Acid Anticoagulants Calcium Chelating Agents Chelating Agents Sequestering Agents Molecular Mechanisms of Pharmacological Action Vitamin B Complex Vitamins Micronutrients Physiological Effects of Drugs |