Solid Tumors Clinical Trial
Official title:
Dose-escalation, PK- and Safety Study With Single Agent CetuGEX™ in Patients With EGFR Positive Locally Advanced and/or Metastatic Cancer
Verified date | May 2021 |
Source | Glycotope GmbH |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
This was a prospective, open label, multicenter study evaluating the safety, tolerability and pharmacokinetics of CetuGEX™ after intravenous administration in patients with EGFR positive, locally advanced and/or metastatic solid cancers. The effect of CetuGEX™ on the development of anti-drug antibodies and on tumour response was also evaluated.
Status | Completed |
Enrollment | 41 |
Est. completion date | October 2013 |
Est. primary completion date | August 2012 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: 1. Male or female and age = 18 yrs 2. Histologically confirmed EGFR positive locally advanced and/or metastatic solid organ tumour 3. Measurable or non-measurable tumour 4. Failure of standard therapy or non-availability of standard therapy (Patients must have received at least 1 line of chemotherapy and further standard therapy is not an option at study entry) 5. All anti-tumour therapies must be completed 4 weeks before start of study treatment; treatment with Cetuximab must be completed at least 6 weeks prior to study start 6. ECOG Performance Status =1 and estimated life expectancy of = 3 months 7. Adequate organ function: - Bone marrow function: hemoglobin = 100 g/L; white blood cell count (WBC) = 3.0 x 10^9/L; absolute neutrophil count (ANC) = 1.5 x 10^9/L; platelet count = 100 x 10^9/L - Hepatic: aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) = 2.5 times upper limit of normal (ULN) (= 5 x ULN if hepatic metastases present); bilirubin = 1.5 x ULN; alkaline phosphatase = 5.0 x upper limit of normal (ULN) - Renal: creatinine < 1.5 x ULN 8. Patients of both genders with procreative potential must use effective contraception while enrolled in the study and for at least 4 weeks after the last study drug infusion 9. Written informed consent must be obtained prior to conducting any study-specific procedures For Expansion Phase only: 10. No prior treatment with Cetuximab allowed Exclusion Criteria: 1. Chemotherapy, radiation, other anti-cancer therapies including any investigational agents at the study enrolment within 4 weeks prior to study enrolment 2. Concurrent anti-tumour therapy or concurrent immunotherapy 3. Concurrent systemic steroids except topical (inhaled, topical, nasal) or replacement therapy for the last 28 days. 4. Major surgery within 4 weeks prior entering the study and/or incomplete recovery from surgery or planned major surgery 5. Primary or secondary immune deficiency 6. Clinically active infections > CTCAE grade 2 7. Prior allergic reaction to a monoclonal antibody (e.g. Trastuzumab, Cetuximab or Bevacizumab). 8. Active hepatitis B assessed by serology, hepatitis C by histology; human immunodeficiency virus (HIV) seropositivity 9. Any concurrent malignancy other than basal cell carcinoma or carcinoma in situ of the cervix. Patients with a previous malignancy but without evidence of disease for = 3 years will be allowed to enter the study. 10. Uncontrolled medical condition considered as high risk for the treatment with an investigational drug including unstable diabetes mellitus, vena-cava-syndrome, chronic symptomatic respiratory disease. 11. Clinical signs of brain metastasis or leptomeningeal involvement 12. Symptomatic congestive heart failure (New York Heart Association [NYHA] 3 or 4); unstable angina pectoris within 6 months prior to enrollment; significant cardiac arrhythmia, or history of stroke or transient ischemic attack within 1 year. 13. Active drug abuse or chronic alcoholism 14. Pregnancy or Breastfeeding |
Country | Name | City | State |
---|---|---|---|
Germany | Glycotope Investigational Site | Hamburg | |
Germany | Glycotope Investigational Site | Heidelberg | |
Italy | Glycotope Investigational Site | Milan | |
Italy | Glycotope Investigational Site | Milan | |
Switzerland | Glycotope Investigational Site | Bellinzona |
Lead Sponsor | Collaborator |
---|---|
Glycotope GmbH |
Germany, Italy, Switzerland,
Fiedler W, Cresta S, Schulze-Bergkamen H, De Dosso S, Weidmann J, Tessari A, Baumeister H, Danielczyk A, Dietrich B, Goletz S, Zurlo A, Salzberg M, Sessa C, Gianni L. Phase I study of tomuzotuximab, a glycoengineered therapeutic antibody against the epide — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Incidence of Treatment-Emergent Adverse Events (TEAE) assessed with the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 | TEAE were coded by use of Medical Dictionary for Regulatory Activities (MedDRA) version 13.1 | throughout the study until 28±2 days after last infusion | |
Primary | Incidence of clinically relevant abnormal clinical laboratory parameters | graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 | from first infusion until 28±2 days following the last infusion | |
Primary | Dose-limiting toxicities (DLT) | DLTs were defined as drug-related: Hematological or non-hematological toxicity grade 3 (excl. rash) or 4 excluding inadequately treated nausea and vomiting; In case of skin reaction (rash) grade 4 |
from first infusion until 28±2 days following the last infusion | |
Primary | Changes of corrected QT interval (QTc) duration | by use of 12-lead electrocardiograms (ECG) | from first infusion until 28±2 days following the last infusion | |
Primary | To define the recommended phase II dose and regimen | Defining a recommended dose for a Phase II study was possible based on the available PK data in combination with the safety and activity data for CetuGEX™ | from first infusion until 28±2 days following the last infusion | |
Secondary | Anti-Tumor Activity: Confirmed Best Overall Response Rates | Assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. Tumors were measured by computed tomography (CT) scan or magnetic resonance imaging (MRI) | From date of randomization until the date of first documented progression, assessed up to 60 months | |
Secondary | Anti-Tumor Activity: Clinical Benefit Rates | Assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. Tumors were measured by computed tomography (CT) scan or magnetic resonance imaging (MRI) | From date of randomization until the date of first documented progression, assessed up to 60 months | |
Secondary | Eastern Cooperative Oncology Group (ECOG) Performance Status | The ECOG Scale of Performance Status describes a patient's level of functioning in terms of their ability to care for themself, daily activity, and physical ability (walking, working, etc.). The scale comprises six grades: 0 Fully active, able to carry on all pre-disease performance without restriction Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours Completely disabled; cannot carry on any selfcare; totally confined to bed or chair Dead |
From date of randomization until 28 days ± 2 days after the end of treatment | |
Secondary | Pharmacokinetics (PK): Area under the serum concentration-time curve (AUC) | PK of CetuGEX™ after single and multiple administration | Prior to 1st infusion, end of 1st infusion, 4 hours after end, 72 and 168 hours after start of 1st infusion, then before and after each infusion up to 10 weeks | |
Secondary | Pharmacokinetics (PK): Maximum serum concentration (Cmax) | PK of CetuGEX™ after single and multiple administration | Prior to 1st infusion, end of 1st infusion, 4 hours after end, 72 and 168 hours after start of 1st infusion, then before and after each infusion up to 10 weeks | |
Secondary | Pharmacokinetics (PK): Time to maximum serum concentration (tmax) | PK of CetuGEX™ after single and multiple administration | Prior to 1st infusion, end of 1st infusion, 4 hours after end, 72 and 168 hours after start of 1st infusion, then before and after each infusion up to 10 weeks | |
Secondary | Pharmacokinetics (PK): Minimal serum concentration (Cmin) | PK of CetuGEX™ after single and multiple administration | Prior to 1st infusion, end of 1st infusion, 4 hours after end, 72 and 168 hours after start of 1st infusion, then before and after each infusion up to 10 weeks | |
Secondary | Pharmacokinetics (PK): Terminal elimination half-life (t1/2) | PK of CetuGEX™ after single and multiple administration | Prior to 1st infusion, end of 1st infusion, 4 hours after end, 72 and 168 hours after start of 1st infusion, then before and after each infusion up to 10 weeks | |
Secondary | Pharmacokinetics (PK): Clearance rate (CL) | PK of CetuGEX™ after single and multiple administration | Prior to 1st infusion, end of 1st infusion, 4 hours after end, 72 and 168 hours after start of 1st infusion, then before and after each infusion up to 10 weeks | |
Secondary | Pharmacokinetics (PK): Volume of distribution (Vz) | PK of CetuGEX™ after single and multiple administration | Prior to 1st infusion, end of 1st infusion, 4 hours after end, 72 and 168 hours after start of 1st infusion, then before and after each infusion up to 10 weeks |
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