Clinical Trial 18811

Cancer Type: Thoracic
Interventions:ADI-PEG 20; Alimta (Pemetrexed); Paraplatin (carboplatin); Pemetrexed; Placebo; carboplatin; cisplatin

Study Type: Treatment
Phase of Study: Phase II/III
Investigators:

  • Scott Antonia

Overview

Study Title

Randomized, Double-Blind, Phase 2/3 Study in Subjects with Malignant Pleural Mesothelioma with Low Argininosuccinate Synthetase 1 Expression to Assess ADI-PEG 20 with Pemetrexed and Cisplatin (ATOMIC-Meso Phase 2/3 Study)

Summary

The purpose of the research study is to assess the effectiveness, safety and tolerability (good and/or bad effects) of the study drug ADI-PEG 20 when given in combination with pemetrexed and cisplatin to participants with mesothelioma. Investigators will also see how many people have tumor shrinkage, how long people live and how long they live without their tumors getting worse with both treatments.

Objective

The primary objective of this study is: Determine efficacy as determined by response rate (RR), measured by modified RECIST and RECIST 1.1 criteria (phase 2 portion), and PFS (phase 3 portion). The secondary objectives of this study are: Assessment of safety and tolerability of ADI-PEG 20 in combination with pemetrexed and cisplatin. Determine duration of response. Assess overall survival (OS). 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.

Inclusion Criteria

  • Histologically proven advanced MPM of biphasic or sarcomatoid histology. Biphasic Malignant Pleural Mesothelioma (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.
  • Naïve to prior chemotherapy or immunotherapy (i.e., this is a first-line systemic therapy study).
  • Malignant Pleural Mesothelioma (MPM) tumor sample for determination of ASS1 status. ASS1-deficiency is not required for study entry at study start, but tumor sample for ASS1 status is required. This study will employ an adaptive biomarker-driven design with an interim analysis to be conducted at the end of the phase 2 portion. The interim analysis will evaluate the treatment effect of ADI PEG 20 in combination with pemetrexed and cisplatin on overall survival (OS) in the overall population (biphasic and sarcomatoid histology patients) and pre-defined subpopulation of biomarker-positive patients (ASS1-deficient subpopulation). Thus ASS1 deficiency may be required for the phase 3 portion of the study, pending the interim analysis. ASS1-deficiency, demonstrated on tissue specimen (cytospin samples are not acceptable), will be defined in the laboratory manual. If archived tissue is not sufficient or not available, then tissue must be obtained by biopsy.
  • Measurable disease as assessed by modified RECIST for MPM for thoracic disease and Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for extra-thoracic disease.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1.
  • Predicted life expectancy of at least 12 weeks.

  • Exclusion Criteria

  • Radiotherapy (except for palliative reasons) the previous two weeks before.
  • 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.
  • Serious infection requiring treatment with intravenous antibiotics at the time of study entrance, or an infection requiring intravenous therapy within 7 days prior.
  • Known to be serologically positive for human immunodeficiency virus (HIV). Testing to determine possible infection status is not required.