Advanced metastatic colorectal cancer (stage IV) MedDRA version: 17.1 Level: PT Classification code 10010035 Term: Colorectal cancer stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Modufolin® powder for solution for injection 100 mg
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: Modufolin API
Current Sponsor code: Modufolin API
Other de
Sponsors
Isofol Medical AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Advanced metastatic colorectal (Stage IV) cancer verified by biopsy 2) CT-scan or MRI of thorax, abdomen and pelvis; within four ( 3 months 6) Adequate haematological function: a) Haemoglobin (Hb) > 100 g/L, b) Absolute neutrophil count (ANC) > 1.5x109/L, and c) Platelets > 100x109/L 7) Adequate renal and hepatic functions: a) Creatinine clearance > 50 mL/min, b) Total bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range 18
Exclusion criteria
Exclusion criteria: 1) Tumours other than colorectal adenocarcinomas (current or within the previous 5 years), with the exception for curatively treated non melanoma skin cancer or in situ carcinoma of the cervix. 2) Adjuvant treatment of CRC within the last 12 months. 3) Evidence of central nervous system metastases 4) Unresolved bowel obstruction or sub-obstruction, uncontrolled Crohn’s disease or ulcerative colitis 5) History of cardiac disease with a New Your 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 6) Current severe chronic diarrhoea 7) Current chronic infection or uncontrolled serious illness causing immunodeficiency 8) Any current uncontrolled serious illness or medical condition 9) Current major psychiatric disorder (e.g. major depression, psychosis) 10) Participation in another clinical study with an IMP within one (1) month prior to inclusion 11) Known intolerance to fluoropyrimidine therapy suggestive of dihydropyrimidine dehydrogenase deficiency 12) Suspicion of hypersensitivity or allergy to the IMP, or to products chemically related to the IMP (i.e. folate derivatives) 13) Female patients: currently pregnant or breast-feeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 8 weeks;Main Objective: - To characterise the tolerability of Modufolin® in Stage IV CRC patients in terms of toxicity during eight (8) weeks of treatment with one (1) of two (2) dose levels of Modufolin® (30 and 60 mg/m2) in combination either with 5-FU (500 mg/m2) alone (Arm #1), with Oxaliplatin (85 mg/m2) and 5-FU (500 mg/m2) (Arm #2), or with Irinotecan (180 mg/m2) and 5-FU (500 mg/m2) (Arm #3);Secondary Objective: - To characterise all adverse events (AEs) and clinically significant abnormal laboratory test result changes regardless of attribution during the entire study period. - To evaluate tumour response and disease progression by means of Objective Response Rate (ORR) at the end of study participation. - To assess the level of overall inhibition of thymidylate synthase (TS) as reflected by change of deoxyuridine (dU) levels from before and 24 hours after administration of the combination treatment on Day 1 in Cycle #1 and in Cycle #4 in a subset of patients. - To determine the pharmacokinetic characteristics of methylenetetrahydrofolate (MTHF), methyl-tetrahydrofolate (methyl-THF), and tetrahydrofolate (THF) calculated from plasma samples in each cohort following Modufolin® administration on Day 1 in Cycle #1 and in Cycle #4.;Primary end point(s): - Number and severity of dose limiting toxicity (DLT) associated with the administration of the administered chemotherapeutic agents or any other significant AEs at each Modufolin® dose level. - Number of patients with adjusted chemotherapeutic agent dose (i.e. 5-FU, Oxaliplatin and/or Irinotecan) due to presence of related toxicity in the individual treatment cohorts. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 8 weeks;Secondary end point(s): - Number and severity of AEs or clinically significant abnormal laboratory test result changes regardless of causal relationship - Determination of Objective Response Rate (ORR) after four (4) cycles of chemotherapy. - Deoxyuridine (dU) levels before and 24 hours after administration of the combination treatment on Day 1 in the first and in the last chemotherapy cycle of a subset of patients. - Plasma pharmacokinetics of 5,10- Methylene Tetrahydrofolate (MTHF), 5-Methyl Tetrahydrofolate (5-methyl-THF), and Tetrahydrofolate (THF), directly prior, and at 10 minutes, at 1, 2, and 4 hours in each cohort following Modufolin® administration on Day 1 in Cycle #1 and in Cycle #4 | — |
Countries
Denmark, Greece, Norway, Sweden
Contacts
Public ContactLouise Kvistgaard
Isofol Medical AB
Outcome results
None listed