Phase 2/3 Study in Subjects with Malignant Pleural Mesothelioma to determine the treatment effect of ADI-PEG 20 or Placebo given in combination with Pemetrexed and Cisplatin.
- Conditions
- Advanced malignant pleural mesothelioma (MPM)MedDRA version: 21.0Level: LLTClassification code 10035605Term: Pleural mesothelioma malignant advancedSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-004281-28-GB
- Lead Sponsor
- Polaris Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 386
1.Histologically proven unresectable 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).
2.Naïve to prior chemotherapy or immunotherapy (i.e., this is a first-line systemic therapy study).
3.Measurable disease as assessed by modified RECIST for MPM local pleural disease (Appendix A) and RECIST 1.1 for metastatic lesions (Appendix B).
4.ECOG performance status of 0 – 1 (Appendix C).
5.Predicted life expectancy of at least 12 weeks.
6.Age = 18 years (there is no upper age limit).
7.Fully recovered from any prior surgery and no major surgery within 4 weeks. Surgery for placement of vascular access devices is acceptable.
8.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.
9.Informed consent must be obtained prior to study initiation.
10.Hemoglobin (HB) > 9.0 g/dL.
11.Absolute neutrophil count (ANC) > 1,500/µL.
12.Platelets > 75,000/µL.
13.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
14.Serum uric acid = 10 mg/dL (595 µmol/L) (with or without medication control).
15.Creatinine clearance = 45 mL/min (estimated, using Cockcroft and Gault formula). Cisplatin dose adjustment is recommended for subjects with a creatinine clearance between 45 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 45 – 49.9 mL/min.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
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
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 malignancy with no known active disease present in the opinion of the Investigator will not affect patient outcome.
10.Allergy to cisplatin or other platinum-containing compounds.
11.Pregnancy or lactation.
12.Expected non-compliance.
13.Subjects who had been treated with ADI-PEG 20 previously.
14.History of uncontrolled 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).
18.Allergy to pemetrexed or to any other ingredient used in the formulation.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method