Solid Tumors
Conditions
Keywords
advanced solid cancers, metastatic solid cancers
Brief summary
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.
Detailed description
Male or female patients ≥18 years of age with a histologically confirmed locally advanced and/or metastatic solid organ tumor. Patients enrolled in Germany were required to have a positive EGFR overexpression status. Patients must have experienced a failure or non-availability of standard therapy (had received at least one line of chemotherapy and further standard therapy was not an option at study entry). Open-label, non-randomized, inter-patient dose-escalation, multi-center study. Patients were to receive CetuGEX until disease progression or until intolerable toxicities occurred.
Interventions
DRUGCetuGEX™
Sponsors
Glycotope GmbH
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events (TEAE) assessed with the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 | throughout the study until 28±2 days after last infusion | TEAE were coded by use of Medical Dictionary for Regulatory Activities (MedDRA) version 13.1 |
| Incidence of clinically relevant abnormal clinical laboratory parameters | from first infusion until 28±2 days following the last infusion | graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 |
| Dose-limiting toxicities (DLT) | from first infusion until 28±2 days following the last infusion | 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 |
| Changes of corrected QT interval (QTc) duration | from first infusion until 28±2 days following the last infusion | by use of 12-lead electrocardiograms (ECG) |
| To define the recommended phase II dose and regimen | from first infusion until 28±2 days following the last infusion | 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™ |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Time to maximum serum concentration (tmax) | 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 | PK of CetuGEX™ after single and multiple administration |
| Pharmacokinetics (PK): Minimal serum concentration (Cmin) | 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 | PK of CetuGEX™ after single and multiple administration |
| Anti-Tumor Activity: Confirmed Best Overall Response Rates | From date of randomization until the date of first documented progression, assessed up to 60 months | 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) |
| Pharmacokinetics (PK): Clearance rate (CL) | 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 | PK of CetuGEX™ after single and multiple administration |
| Pharmacokinetics (PK): Volume of distribution (Vz) | 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 | PK of CetuGEX™ after single and multiple administration |
| Pharmacokinetics (PK): Terminal elimination half-life (t1/2) | 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 | PK of CetuGEX™ after single and multiple administration |
| Anti-Tumor Activity: Clinical Benefit Rates | From date of randomization until the date of first documented progression, assessed up to 60 months | 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) |
| Eastern Cooperative Oncology Group (ECOG) Performance Status | From date of randomization until 28 days ± 2 days after the end of treatment | 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 1. 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 2. Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours 3. Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours 4. Completely disabled; cannot carry on any selfcare; totally confined to bed or chair 5. Dead |
| Pharmacokinetics (PK): Area under the serum concentration-time curve (AUC) | 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 | PK of CetuGEX™ after single and multiple administration |
| Pharmacokinetics (PK): Maximum serum concentration (Cmax) | 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 | PK of CetuGEX™ after single and multiple administration |
Countries
Germany, Italy, Switzerland
Outcome results
None listed