Advanced malignant pleural mesothelioma (MPM) MedDRA version: 21.0 Level: LLT Classification code 10035605 Term: Pleural mesothelioma malignant advanced System Organ Class: 100000004864
Conditions
Interventions
Product Name: ADI-PEG 20
Product Code: [ADI-PEG 20]
Pharmaceutical Form: Solution for injection
INN or Proposed INN: ADI-PEG 20
Current Sponsor code: ADI-PEG 20
Other descriptive name: Pegargiminase [
Sponsors
POLARIS GROUP
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Histologically proven not resecable MPM of biphasic or sarcomatoid histology. Biphasic MPM is defined using the World Health Organization’s international histological classification of tumors as containing an epithelial and a sarcomatoid component with each component comprising at least 10% of the tumor (Corson 2004, Allen 2005). Naïve to prior chemotherapy or immunotherapy (i.e., this is a first-line systemic therapy study). Measurable disease by modified RECIST criteria for MPM for local pleural disease and RECIST 1.1 criteria for metastatic lesions ECOG performance status of 0 – 1 (Appendix C). Predicted life expectancy of at least 12 weeks. Age = 18 years (there is no upper age limit). Fully recovered from any prior surgery and no major surgery within 4 weeks. Surgery for placement of vascular access devices is acceptable. Subjects and their partners must be asked to use appropriate contraception. They must agree to use two forms of contraception or agree to refrain from intercourse for the duration of the study and for 35 days after last dose of ADI-PEG 20 or for at least six months after treatment with pemetrexed and cisplatin whichever is the longer duration. Females must not be pregnant at the start of the study, and a serum human chorionic gonadotropin (HCG) pregnancy test must be negative before entry into the study. If positive HCG pregnancy test, further evaluation to rule out pregnancy must be performed according to GCP before this patient is claimed eligible. Informed consent must be obtained prior to study initiation. Hemoglobin (HB) > 9.0 g/dL. Absolute neutrophil count (ANC) > 1,500/µL. Platelets > 75,000/µL. Either: (i) serum bilirubin = 1.5 x upper limit of normal (ULN) or (ii) alanine aminotransferase (ALT), aspartate aminotransferase (AST) and/or alkaline phosphatase (ALP) = 3 x (ULN) unless raised due to tumor in which case up to 5 x ULN is permissible Serum uric acid = 10 mg/dL (595 µmol/L) (with or without medication control). Creatinine clearance = 40 mL/min (estimated, using Cockcroft and Gault formula). Cisplatin dose adjustment is recommended for subjects with a creatinine clearance between 40 and 59 mL/min (Bennis 2014) as follows: reduce cisplatin dose by 25% for clearance between 50 59.9 mL/min and by 50% for clearance between 40 – 49.9 mL/min. 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 116 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 270
Exclusion criteria
Exclusion criteria: 1. Radiotherapy (except for palliative reasons) the previous two weeks before. 2. Ongoing toxic manifestations of previous treatments. 3. Symptomatic brain or spinal cord metastases (patients must be stable for > 1 month post radiotherapy or surgery). 4. Major thoracic or abdominal surgery from which the patient has not yet recovered. 5. Serious infection requiring treatment with intravenous antibiotics at the time of study entrance, or an infection requiring intravenous therapy within 7 days prior. 6. Known to be serologically positive for human immunodeficiency virus (HIV). Testing to determine possible infection status is not required. 7. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association Class III or IV), symptomatic cardiac arrhythmia, previous history of myocardial infarction (unless stable and good ejection fraction on echocardiogram) or psychiatric illness, and social situations that would limit compliance with study requirements. 8. Is a participant of, or plans to participate in, another interventional clinical study whilst taking part in this study. Participation in an observational or biomarker study would be acceptable, with prior Sponsor approval. 9. Subjects with history of another primary cancer, including co-existent second malignancy, with the exception of: a) curatively resected non-melanoma skin cancer; b) curatively treated cervical carcinoma in situ; or c) other primary solid tumor with no known active disease present in the opinion of the Investigator will not affect patient outcome. 10. Allergy to platinum salts. 11. Pregnancy or lactation. 12. Expected non-compliance. 13. Subjects who had been treated with ADI-PEG 20 previously. 14. History of seizure disorder not related to underlying cancer. 15. ECOG performance status > 2. 16. Allergy to pegylated compounds. 17. Allergy to E. coli drug products (such as GMCSF).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Determine effectiveness of study treatment by looking at response rate (RR), as measured by modified RECIST and RECIST 1.1 criteria (phase 2 portion), and overall survival (phase 3 portion). Modified RECIST and RECIST 1.1 criteria were developed as standards to assess the response in patients with cancer, based on measurement of viable tumor on scans [computed tomography (CT) and magnetic resonance imaging (MRI)]. Overall survival is the percentage of people in a study or treatment group who are still alive for a certain period of time after they started treatment for a disease, such as cancer. ;Secondary Objective: Key Secondary objective - Phase 2: -Determine the duration of response (DOR) Key Secondary objective for Phase 3 is: -Assess progression free survival (PFS) Other Secondary objectives: -Assessment of safety and tolerability of ADI-PEG 20 in combination with pemetrexed and cisplatin (standard-of-care) -Determine the pharmacokinetics (how the body affects the drug) of ADI-PEG 20 -Determine the pharmacodynamics (how the drug affects the body) of ADI-PEG 20 in combination with pemetrexed and cisplatin -Determine the immunogenicity of ADI-PEG 20 in combination with pemetrexed and cisplatin;Primary end point(s): The primary objective of this study is: • Determine efficacy as determined by the objective response rate (RR), measured by modified RECIST and RECIST 1.1 criteria (phase 2 portion), and OS (phase 3 portion). The goal of the phase 2 portion of the trial is to provide data to support accelerated approval by the United States Food & Drug Administration, and the goal of the phase 3 portion of the trial is to provide a confirmatory study that would be ongoing at the time of the marketing application. ;Timepoint(s) of evaluation of this end point: Scans will be performed every 6 weeks through Week 18 and during the Single Agent dosing period, scans will be every 8th weekly dose of ADI-PEG 20/placebo. Confirmatory scans are no longer requ | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The key secondary objective of the phase 2 portion is: • Determine the duration of response The key secondary objective of the phase 3 portion is: • Assess progression free survival (PFS) Other secondary objectives of this study include: • Assessment of safety and tolerability of ADI-PEG 20 in combination with pemetrexed and cisplatin • Determine the pharmacodynamics of ADI-PEG 20 in combination with pemetrexed and cisplatin • Determine the immunogenicity of ADI-PEG 20 in combination with pemetrexed and cisplatin • Determine the pharmacokinetics of ADI-PEG 20 in combination with pemetrexed and cisplatin;Timepoint(s) of evaluation of this end point: The secondary objective of the phase 2 (DOR) will be analyzed at the end of the phase 2 portion. The key secondary objective for the phase 3 (PFS) which will be analyzed only if the analysis of OS is statistically significant at the final analysis, with alpha level of 0.05 (two-sided) using the same statistical methodologies as applied to OS. Safety and tolerability will be monitored throughout the study by lead investigators, sponsor, and DSMB (as outlined in Charter). A complete evaluation of these and other secondary objectives will be conducted at the interim analysis and/or final analysis. | — |
Countries
Australia, Italy, United Kingdom, United States
Contacts
Public ContactKristy Lu
Polaris Pharmaceuticals, Inc.
Outcome results
None listed