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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

Phase 1/Phase 2
18 Years
Open (Enrolling)
Advanced Metastatic (Stage IV) Colorectal Cancer

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Trial Information

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

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.

Inclusion Criteria:

- Advanced metastatic colorectal (stage IV) cancer verified by biopsy within 12 months
prior to signing consent

- Chemotherapy-naive patients or patients who received chemotherapy in an adjuvant
setting that ended at least 6 months prior to signing consent. No previous treatment
with oxaliplatin

- CT-scan or MRI of thorax, abdomen and pelvis; within ≤4 weeks before start of

- Evaluable disease and one measurable site of disease according to RECIST 1.1 criteria
(at least 10 mm for CT-scan or MRI)

- Neurological examination with no 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 10^9/L, platelets ≥ 100
x 10^9/L

- Serum calcium, magnesium, zinc and potassium within normal limits

- Adequate renal and hepatic functions: creatinine clearance >50 cc/min, total
bilirubin ≤ 1.25 times upper normal limits, ASAT and ALAT ≤ 3 times upper normal

- INR ≤1.5x 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 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

- Current chronic diarrhoea

- Any known chronic infection or chronic illness causing immunodeficiency

- Any uncontrolled serious illness or medical condition

- Existing peripheral neuropathy

- 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)

- Cirrhosis or history of obstructive jaundice

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Outcome Measure:

Change in Absolute Neutrophil count from both baseline and in between readings

Outcome Description:

As defined by neutropenia

Outcome Time Frame:

Every second week, in 16 weeks and thereafter every 12th week for up to 12 months

Safety Issue:



United States: Food and Drug Administration

Study ID:




Start Date:

September 2012

Completion Date:

December 2014

Related Keywords:

  • Advanced Metastatic (Stage IV) Colorectal Cancer
  • Metastatic colorectal cancer
  • stage IV
  • Chemotherapy
  • PledOx
  • Mangafodipir
  • Febrile neutropenia
  • Oxidative stress
  • Antioxidant
  • neutropenia
  • Colorectal Neoplasms