Pemetrexed Disodium and Cisplatin Followed by Surgery With or Without Radiation Therapy in Treating Patients With Malignant Pleural Mesothelioma
Condition: Malignant Mesothelioma
MeSH terms: Mesothelioma; Mesothelioma, Malignant
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: Drugs used in chemotherapy, such as pemetrexed disodium and cisplatin, work in
      different ways to stop the growth of tumor cells, either by killing the cells or by stopping
      them from dividing. Giving chemotherapy before surgery may make the tumor smaller and reduce
      the amount of normal tissue that needs to be removed. Radiation therapy uses high-energy
      x-rays to kill tumor cells. Giving radiation therapy after surgery may kill any tumor cells
      that remain after surgery.

      PURPOSE: This randomized phase II trial is studying how well giving pemetrexed disodium
      together with cisplatin followed by surgery with or without radiation therapy works in
      treating patients with malignant pleural mesothelioma.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Evaluate the short-term outcomes and feasibility of neoadjuvant therapy with pemetrexed
           disodium and cisplatin followed by extrapleural pneumonectomy in patients with malignant
           pleural mesothelioma.

        -  Evaluate the long-term outcomes and feasibility of postoperative hemithoracic
           radiotherapy in patients with R0 or R1 resection.

      Secondary

        -  Determine the quality of life of these patients.

        -  Identify predictive and prognostic markers in these patients.

        -  Determine relapse-free or progression-free survival and overall survival of these
           patients.

        -  Collect tissue and blood from these patients.

      OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
      participating center, histology (sarcomatous or other vs epithelial or mixed histology),
      nodal status (N0-1 vs N2), and extent of disease (T1-2 vs T3).

        -  Part 1 (neoadjuvant therapy and surgery): Patients receive pemetrexed disodium IV over
           10 minutes and cisplatin IV over 2 hours on day 1. Treatment repeats every 21 days for 3
           courses in the absence of disease progression or unacceptable toxicity. Within 8 weeks
           after completion of neoadjuvant therapy, patients without progressive disease undergo
           extrapleural pneumonectomy.

        -  Part 2 : Patients achieving R0 or R1 resection proceed to part 2 of study treatment and
           are randomized to 1 of 2 treatment arms. Patients with R2 resection, disease
           progression, or symptomatic deterioration after treatment in part 1 are taken off study.

             -  Arm I (no postoperative radiotherapy): Patients do not undergo radiotherapy.
                Quality of life is assessed at baseline and at 6, 10, 16, and 22 weeks after
                randomization.

             -  Arm II (postoperative radiotherapy): Beginning within 10 weeks after surgery,
                patients undergo radiotherapy to the hemithoracic region 5 days a week for
                approximately 5 weeks in the absence of disease progression or unacceptable
                toxicity. Quality of life is assessed at baseline and at 4, 8, 14, and 20 weeks
                after initiation of radiotherapy.

      Patients undergo blood and tissue collection at registration and surgery for laboratory and
      biomarker analysis.

      After completion of study treatment, patients are followed periodically for up to 5 years
      after surgery.

      PROJECTED ACCRUAL: A total of 155 patients will be accrued for this study.
    

Intervention name(s): Cisplatin; Pemetrexed; Therapeutic conventional surgery; Radiotherapy
Intervention type(s): Drug; Drug; Procedure; Radiation
Intervention description(s): Cisplatin 75 mg/m2 i.v. over approximately 2 hours on day 1 every 21 days; Pemetrexed 500 mg/m2 i.v. over approximately 10 minutes on day 1 every 21 days; Extrapleural pneumonectomy; CTV1 will receive 45 or 46 Gy. CTV2 will be treated up to a total dose of 55,9 to 56,2 Gy.
Intervention MeSH terms: Pemetrexed
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: epithelial mesothelioma; sarcomatous mesothelioma; stage IA malignant mesothelioma; stage IB malignant mesothelioma; stage II malignant mesothelioma; stage III malignant mesothelioma