A multicenter phase II study to evaluate safety and efficacy of glutadon once weekly (GDO) in patients with metastatic colorectal cancer resistant or intolerable to approved chemo- and molecular-targeted therapies

• Conditions: 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: 12.1Level: LLTClassification code 10052362Term: Metastatic colorectal cancer

• Registration Number: EUCTR2009-017871-13-PL
• Lead Sponsor: ew Medical Enzymes AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-04-30
• Last Update Posted: 21 January 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

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

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified