Adult patients with unresectable or metastatic colorectal cancer showing progression of disease on at least one fluoropyrimidine derivative, oxaliplatin, irinotecan and EGFR-antibodies (cetuximab or panitumumab) or demonstrating intolerance to the drugs. Patients who are considered no candidates for EGFR-antibodies (e.g. patients with K-ras mutations) are eligible for the study in the absence of prior EGFR-antibody treatment. Prior treatment with bevacizumab is allowed. MedDRA version: 12.1 Lev
Conditions
Interventions
Product Name: PEGylated Pseudomonas 7A glutaminase-asparaginase
Product Code: PEG-PGA
Pharmaceutical Form: Powder for solution for infusion
Current Sponsor code: PEG-PGA
Concentration unit: IU interna
Sponsors
New Medical Enzymes AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Age = 18 years at visit 1 (day -3) Histologically confirmed diagnosis of colorectal cancer that is unresectable and/or metastatic and therefore not amenable to surgery or combined modality with curative intent Prior treatment with a fluoropyrimidine (5-fluorouracil and/or capecitabine), oxaliplatin, irinotecan or documented intolerance or ineligibility to the drugs K-RAS mutation or previous therapy with EGFR antagonists (e.g. cetuximab or panitumumab) At least one measurable site of disease on CT/MRI scan at screening ECOG Performance Status of 0 or 1 Patients must have normal organ and marrow function: 1. White blood cell count (WBC) = 3.5x 109/L; 2. Platelets = 100 x 109/L; Hb > 9 g/dl 3. ALT and AST = 2.5 x upper limit of normal (ULN) or = 5.0 x ULN if considered due to tumor; 4. Alkaline phosphatase = 2.5 x ULN unless considered due to tumor; 5. Serum bilirubin = 1.5 x ULN; 6. Serum lipase and amylase = 1.5 x ULN or = 5.0 x ULN if considered due to tumor; 7. Serum creatinine = 1.5 x ULN or 24-hour creatinine clearance = 50 ml/min. (calculated creatinine clearance using Cockroft formula is acceptable) Ability to understand and willingness to sign a written informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Patients had > 3 previous systemic therapies for metastatic disease Prior treatment with glutadon, PEG-PGA or DON Known hypersensitivity to PEG-PGA and/or DON Treatment with any cytotoxic and/or investigational cytotoxic drug = 4 weeks (6 weeks for nitrosurea or mitomycin C) prior to Visit 1 (day -3) Previous malignancy (other than colorectal cancer) in the last 5 years except basal cell cancer of the skin, pre-invasive cancer of the cervix or superficial bladder tumor [Ta, Tis and T1]. Impaired cardiac function defined as congestive heart failure NYHA > class II, any clinically significant brady- or tachycardia, myocardial infarction within 12 months prior to Visit 1, or any other clinically significant heart disease (e.g., unstable angina or uncontrolled hypertension) Patients with severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol Abnormal electrolyte (Serum sodium, potassium and calcium) values that are clinically significant in opinion of the investigator. Patients who have undergone major surgery = 2 weeks prior to Visit 1 (day -3) or who have not recovered from side effects of such therapy Patients who have received wide field radiotherapy = 4 weeks or limited field radiation for palliation < 2 weeks prior to Visit 1 (day -3) or who have not recovered from side effects of such therapy Patients who are pregnant or breast feeding Life expectancy of < 3 months in opinion of the investigator Men or women of child-bearing potential who are sexually active and unwilling to use a medically acceptable method of contraception from the start of treatment up 6 months after end of treatment. Known CNS-metastases Known HIV-infection Patients with a history of severe allergy or hypersensitivity History of seizure disorders or central nervous system disorders Uncontrolled nausea and vomiting Not well or uncontrolled diabetes mellitus in opinion of the investigator Patients unwilling or unable to comply with the protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Safety is the first primary objective The second primary objective is progression free survival;Secondary Objective: Response rate according to RECIST disease control rate (DCR) Glutamine depletion in blood plasma;Primary end point(s): The trial has two primary objectives. Safety is the first primary objective and measured by adverse events according to NCI-CTC, haematology, biochemistry, vital signs (incl. weight). The second primary objective is progression free survival calculated using the Kaplan-Meier method. | — |
Countries
Poland
Outcome results
None listed