Ph 2/3 Study in Subjects With MPM to Assess ADI-PEG 20 With Pemetrexed and Cisplatin (ATOMIC)

Polaris Group

Status and phase: Completed; Phase 3; Phase 2

Conditions: Mesothelioma

Treatments: Drug: ADI-PEG 20 plus Pem Platinum; Other: Placebo plus Pem Platinum

Study type: Interventional

Funder types: Industry

Identifiers

NCT02709512

POLARIS2015-003

Details and patient eligibility

About

This is a study of ADI-PEG 20 (pegylated arginine deiminase), an arginine degrading enzyme versus placebo in patients with malignant pleural mesothelioma. Malignant pleural mesothelioma have been found to require arginine, an amino acid. Thus the hypothesis is that by restricting arginine with ADI-PEG 20, the malignant pleural mesothelioma cells will starve and die.

Enrollment: 249 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically proven unresectable MPM of biphasic or sarcomatoid histology
• Naïve to chemotherapy or immunotherapy
• ECOG PS 0-1
• Expected survival of at least 3 months
• Age 18 years or over (there is no upper age limit)
• Measurable disease by modified RECIST criteria for MPM for local pleural disease and RECIST 1.1 criteria for metastatic lesions
• Written (signed and dated) informed consent and must be capable of co-operating with treatment and follow up
• Adequate hematologic, hepatic, and renal function

Exclusion criteria

• Radiotherapy (except for palliative reasons) in the previous two weeks before study treatment
• History of unstable cardiac disease
• Ongoing toxic manifestations of previous treatments
• Symptomatic brain or spinal cord metastases (patients must be stable for > 1 month post radiotherapy or surgery)
• Major thoracic or abdominal surgery from which the patient has not yet recovered.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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249 participants in 2 patient groups, including a placebo group

Drug: ADI-PEG 20 plus Pem Platinum

Experimental group

Description:

Dose: 36 mg/m2 given weekly Route of Administration: Intramuscular (IM) Duration : Course of Study In Combination With: Pemetrexed Dose: 500 mg/m2 every 3 weeks Route of Administration: Intravenous Cisplatin Dose: 75 mg/m2 every 3 weeks Route of Administration: Intravenous Carboplatin Dose: AUC 5 mg/mL/min every 3 weeks Route of Administration: Intravenous ADI-PEG 20 plus Pem Platinum: Investigational Drug in combination approved standard of care treatment for this indication

Treatment:

Drug: ADI-PEG 20 plus Pem Platinum

Drug: Placebo plus Pem Platinum

Placebo Comparator group

Description:

Dose: 36 mg/m2 given weekly Route of Administration: Intramuscular (IM) Duration : Course of Study In Combination With: Pemetrexed Dose: 500 mg/m2 every 3 weeks Route of Administration: Intravenous Cisplatin Dose: 75 mg/m2 every 3 weeks Carboplatin Dose: AUC 5 mg/mL/min every 3 weeks Route of Administration: Intravenous Placebo plus Pem Platinum: Placebo in combination approved standard of care treatment for this indication

Treatment:

Other: Placebo plus Pem Platinum