Pemetrexed Disodium and Cisplatin Followed by Surgery With or Without Radiation Therapy in Treating Patients With Malignant Pleural Mesothelioma

Swiss Group for Clinical Cancer Research

Status and phase: Completed; Phase 2

Conditions: Malignant Mesothelioma

Treatments: Drug: Pemetrexed; Drug: Cisplatin; Radiation: Radiotherapy; Procedure: Therapeutic conventional surgery

Study type: Interventional

Funder types: Other

Identifiers

NCT00334594

CDR0000481153

2006-000445-19 (EudraCT Number)

LILLY-SAKK-17/04 (Other Identifier)

SWS-SAKK-17/04

EU-20615

SAKK 17/04

Details and patient eligibility

About

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.

Full 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.

Enrollment: 153 patients

Sex: All

Ages: 18 to 69 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed malignant pleural mesothelioma

  • T1-3, N0-2, M0 disease according to International Mesothelioma Interest Group staging system

• No obvious invasion of mediastinal structures by CT scan (e.g., heart, aorta, spine, esophagus)

• No obvious widespread chest wall invasion

  • Resectable chest wall lesions allowed

PATIENT CHARACTERISTICS:

• WHO performance score 0-1
• Fit for neoadjuvant therapy, surgery, and postoperative radiotherapy
• Creatinine clearance > 60 mL/min
• Hemoglobin ≥ 10.0 g/dL
• WBC ≥ 3,500/mm³
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 1.5 times ULN
• Alkaline phosphatase ≤ 1.5 times ULN
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for up to 12 months after completion of study treatment
• FEV_1 ≥ 40% of predicted based on spirometry and lung perfusion scan, if necessary
• No serious underlying medical condition that would preclude study requirements (e.g., active autoimmune disease or uncontrolled diabetes)
• No known hypersensitivity against pemetrexed disodium, cisplatin, or other platinum-containing substances or any other components used for the preparation of the drugs
• No restricted power of hearing (especially in the upper frequency range)
• No acute infections

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy
• No treatment on another clinical trial within the past 30 days
• No prior pleurectomy or lung resection
• No prior radiotherapy of the lower neck, thorax, or upper abdomen
• No aspirin, cyclooxygenase-2 inhibitors, or nonsteroidal anti-inflammatory agents for 5 days prior to, during, and for 2 days after pemetrexed disodium administration
• No other concurrent experimental drugs or anticancer therapy
• No concurrent drugs that would contraindicate study drugs
• No concurrent vaccination against yellow fever

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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153 participants in 2 patient groups

No radiotherapy

Active Comparator group

Treatment:

Drug: Pemetrexed

Procedure: Therapeutic conventional surgery

Drug: Cisplatin

Radiotherapy

Experimental group

Treatment:

Drug: Pemetrexed

Radiation: Radiotherapy

Procedure: Therapeutic conventional surgery

Drug: Cisplatin