Advanced pleural mesothelioma MedDRA version: 16.0 Level: LLT Classification code 10035605 Term: Pleural mesothelioma malignant advanced System Organ Class: 100000004864
Conditions
Interventions
Product Name: Chimeric Antibody to Mesothelin
Product Code: MORAb-009
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: amatuximab
Current Sponsor code: MORAb-009
Other descrip
Sponsors
Morphotek, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Female or male and = 18 years of age. 2. Life expectancy of at least 3 months. 3. Confirmed diagnosis of MPM with the following characteristics: • Unresectable disease (or otherwise not a candidate for curative surgery) • Epithelial type or biphasic (mixed) type with low sarcomatous content. 4. Measurable disease at Screening 5. KPS of = 70% at Screening (Appendix 3). 6. Other significant medical conditions must be well-controlled and stable in the opinion of the investigator for at least 30 days prior to Day 1. 7. Laboratory and clinical results within 2 weeks prior to Day 1 must be as follows: Absolute neutrophil count (ANC) = 1.5 x 109/L Platelet count = 100 x 109/L Hemoglobin = 9 g/dL Serum bilirubin = 1.5 x upper limit of normal (ULN) Aspartate transaminase (AST)* = 2.5 x ULN Alanine transaminase (ALT)* = 2.5 x ULN Alkaline phosphatase * = 3 x ULN Serum creatinine = 2.0 mg/dL * Subjects with liver function abnormalities greater than the ULN specified above are eligible only if, in the opinion of the investigator, these abnormalities are due to disease obstruction of the bile ducts or metastatic disease. Stenting to reduce liver functions to qualifying levels is permitted. 8. Calculated serum creatinine clearance = 60 mL/min using the Cockroft Gault equation (Appendix 7). 9. Female subjects of childbearing potential and all male subjects must be surgically sterile or consent to use a medically acceptable method of contraception throughout the trial and for at least 8 weeks (ie, 5 half-lives of MORAb-009) following administration of the last dose of MORAb 009. 10. Willingness and ability to provide 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 28 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 58
Exclusion criteria
Exclusion criteria: 1. Mesothelioma of the sarcomatous type or disease located primarily in the peritoneum. 2. Prior systemic therapy or radiotherapy for mesothelioma; prior treatment with local radiotherapy for symptom control (ie, non-curative intent) is permitted. 3. Known central nervous system (CNS) tumor involvement. 4. Evidence of other active malignancy requiring treatment. 5. Clinically significant heart disease (e.g., congestive heart failure of New York Heart Association Class 3 or 4 angina not well controlled by medication, or myocardial infarction within 6 months). 6. Active viral hepatitis or symptomatic human immunodeficiency virus (HIV) infection. 7. Clinically significant arrhythmias demonstrated on ECG (Note: Subjects with chronic atrial arrhythmia, i.e., atrial fibrillation or paroxysmal supraventricular tachycardia, are eligible). 8. Active, serious systemic disease, including active bacterial or fungal infection. 9. Treatment within 3 months of the start of the trial with other immunomodulatory therapy (e.g., interferons, immunoglobulin therapy, IL-1RA or systemic corticosteroids). Low-dose treatment with or short term use of systemic corticosteroids, topical or intra-articular steroids is acceptable, subject to the judgment of the investigator. 10. Known hypersensitivity to any of the following: monoclonal antibodies or biologic therapy, pemetrexed or ingredients used in the formulation of pemetrexed, cisplatin or other platinum containing compounds. 12. Subjects who are Breast-feeding, pregnant, or likely to become pregnant during the clinical trial. 13. Subjects who are unable or unwilling to sign the trial informed consent form (ICF).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to determine the effect on PFS of adding MORAb-009 (amatuximab) to the combination of pemetrexed and cisplatin in the treatment of subjects with unresectable malignant pleural mesothelioma (MPM) who have not received prior systemic therapy, as assessed by the modified RECIST for the assessment of response in malignant pleural mesothelioma;Secondary Objective: • Evaluate antitumor activity, as assessed by objective tumor response (overall response rate [ORR]). • Evaluate duration of response (DR). • Evaluate overall survival (OS). • Determine the safety and tolerability of MORAb-009 when administered with pemetrexed and cisplatin. ;Primary end point(s): Primary efficacy endpoint: • PFS at 6 months PFS is defined as time from date of first dose of investigational product to date of disease progression or death due to any cause. Subjects who receive new anti-cancer therapy before disease progression will have their PFS time censored at the date of their last tumor assessment before the new anti-cancer therapy is initiated;Timepoint(s) of evaluation of this end point: PFS at 6m: disease assessed at screening, D8 of the third 21d-cycle, D8 of every third 21d-cycle thereafter, and at the exit visit | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy endpoints: • ORR • DR • OS Exploratory endpoints: • Improvement in Pulmonary Function Tests • Change in Karnofsky Performance Status • Change in CA-125 levels • HLA subtype • Molecular marker analysis • Humoral and T cell responses to mesothelin Safety endpoints: • Assessment of AEs, including AEs of interest (AEIs), clinical laboratory parameters (hematology, serum chemistry and urinalysis), physical examination (including vital sign assessment), 12-lead electrocardiogram (ECG) and human anti-chimeric antibodies (HACA) development. ;Timepoint(s) of evaluation of this end point: PD, DR, ORR: disease assessed at screening, D8 of the third 21d-cycle, D8 of every third 21d-cycle thereafter, and at the exit visit OS: every 4 weeks for the treatment cycles then every month during follow-up | — |
Countries
Canada, Germany, Netherlands, Spain, United States
Contacts
Public ContactMedical Information Department
Eisai Ltd
Outcome results
None listed