Pemetrexed Disodium and Cisplatin Followed By Surgery and Radiation Therapy in Treating Patients With Malignant Pleural Mesothelioma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier:
NCT00227630
First received: September 26, 2005
Last updated: July 17, 2012
Last verified: July 2012
  Purpose

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. Pemetrexed disodium may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy before surgery may shrink the tumor so that it can be removed. Giving radiation therapy after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase II trial is studying how well giving pemetrexed disodium and cisplatin followed by surgery and radiation therapy works in treating patients with malignant pleural mesothelioma.


Condition Intervention Phase
Malignant Mesothelioma
Drug: cisplatin
Drug: pemetrexed disodium
Procedure: adjuvant therapy
Procedure: conventional surgery
Procedure: neoadjuvant therapy
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Primary Purpose: Treatment
Official Title: A Phase II Feasibility Trial of Induction Chemotherapy Followed by Extrapleural Pneumonectomy and Postoperative Radiotherapy in Patients With Malignant Pleural Mesothelioma

Resource links provided by NLM:


Further study details as provided by European Organisation for Research and Treatment of Cancer - EORTC:

Primary Outcome Measures:
  • Feasibility in terms of 90-day progression-free survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Toxicity [ Designated as safety issue: Yes ]
  • Progression-free survival [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]

Enrollment: 59
Study Start Date: July 2005
Primary Completion Date: August 2007 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • Determine the feasibility of neoadjuvant chemotherapy comprising pemetrexed disodium and cisplatin followed by extrapleural pneumonectomy and high-dose postoperative 3D-conformal radiotherapy, in terms of 90-day progression-free survival, in patients with malignant pleural mesothelioma.

Secondary

  • Determine the toxicity of this regimen in these patients.
  • Determine progression-free survival and overall survival of patients treated with this regimen.

OUTLINE: This is a non-randomized, multicenter study.

  • Neoadjuvant chemotherapy: Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1. Treatment repeats every 3 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients are evaluated 3 weeks after completion of neoadjuvant chemotherapy. Patients without disease progression proceed to surgery.
  • Extrapleural pneumonectomy: Within 21-56 days after completion of neoadjuvant chemotherapy, patients undergo extrapleural pneumonectomy. Patients are evaluated 30 days after surgery. Patients without disease progression undergo high-dose 3D-conformal radiotherapy.
  • High-dose 3D-conformal radiotherapy: Beginning 30-84 days after surgery, patients undergo high-dose 3D-conformal radiotherapy daily for 30 days.

After completion of study treatment, patients are followed on days 42 and 90, every 3 months for 1 year, and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 52 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   up to 69 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed malignant pleural mesothelioma

    • All subtypes allowed
  • T1-3, N0-1, M0 disease

    • No N2 or N3 involvement confirmed by mediastinoscopy within 21 days before study entry
  • No clinical invasion of mediastinal structures (e.g., heart, aorta, spine, esophagus)
  • No wide-spread chest wall invasion except focal chest wall lesions
  • No clinical or radiological evidence of shrinking hemithorax
  • No clinically significant third-space fluid (e.g., pleural effusions or ascites) that cannot be managed with thoracentesis or pleurodesis

PATIENT CHARACTERISTICS:

Age

  • Under 70

Performance status

  • WHO 0-1

Life expectancy

  • Not specified

Hematopoietic

  • WBC > 3,500/mm^3
  • Absolute neutrophil count > 1,500/mm^3
  • Platelet count > 100,000/mm^3
  • Hemoglobin ≥ 11 g/dL

Hepatic

  • AST and ALT < 1.5 times upper limit of normal (ULN)
  • Bilirubin < 1.5 times ULN
  • Alkaline phosphatase < 1.5 times ULN

Renal

  • Creatinine clearance ≥ 60 mL/min
  • Acceptable (predicted) post-radiotherapy renal function by semiquantitative isotope renography, with a relative contribution of the contralateral kidney of ≥ 40%

Pulmonary

  • See Disease Characteristics

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after completion of study treatment
  • Deemed to be fit enough to undergo study treatment
  • No preexisting sensory neurotoxicity > grade 1
  • No uncontrolled infection
  • No prior or concurrent melanoma, breast cancer, or hypernephroma
  • No other malignancy within the past 5 years except carcinoma in situ of the cervix or adequately treated basal cell skin cancer
  • No psychological, familial, sociological, or geographical condition that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No concurrent immunotherapy
  • No concurrent routine use of colony-stimulating factors during neoadjuvant chemotherapy

    • Concurrent secondary prophylactic use allowed during neoadjuvant chemotherapy
  • No concurrent secondary prophylactic use of colony-stimulating factors during post-operative radiotherapy

Chemotherapy

  • No prior chemotherapy for mesothelioma

Endocrine therapy

  • No concurrent hormonal cancer therapy

Radiotherapy

  • No prior radiotherapy to the lower neck, thorax, or upper abdomen

Surgery

  • See Disease Characteristics

Other

  • No other concurrent anticancer therapy
  • No other concurrent experimental medications
  • No nonsteroidal anti-inflammatory drugs or salicylates for 2 days before, during, and 2 days after administration of neoadjuvant chemotherapy (5 days before and 2 days after for drugs with a long half-life [e.g., naproxen, piroxicam, diflunisal, or nabumetone])
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00227630

Locations
Belgium
Universitair Ziekenhuis Antwerpen
Edegem, Belgium, B-2650
Italy
Istituto Nazionale per la Ricerca sul Cancro
Genoa, Italy, 16132
Azienda Ospedaliera Di Parma
Parma, Italy, 43100
Universita Degli Studi di Udine
Udine, Italy, 33100
Netherlands
Sint Antonius Ziekenhuis
Nieuwegein, Netherlands, 3435 CM
Daniel Den Hoed Cancer Center at Erasmus Medical Center
Rotterdam, Netherlands, 3008 AE
United Kingdom
Princess Royal Hospital at Hull and East Yorkshire NHS Trust
Hull, England, United Kingdom, HU8 9HE
Edinburgh Cancer Centre at Western General Hospital
Edinburgh, Scotland, United Kingdom, EH4 2XU
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Investigators
Study Chair: Paul Van Schil, MD, PhD Universitair Ziekenhuis Antwerpen
  More Information

Additional Information:
Publications:
Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT00227630     History of Changes
Other Study ID Numbers: EORTC-08031, EORTC-08031, 2004-004273-28
Study First Received: September 26, 2005
Last Updated: July 17, 2012
Health Authority: United States: Federal Government

Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
epithelial mesothelioma
sarcomatous mesothelioma
localized malignant mesothelioma
recurrent malignant mesothelioma

Additional relevant MeSH terms:
Mesothelioma
Neoplasms, Mesothelial
Lung Neoplasms
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Pemetrexed
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Folic Acid Antagonists

ClinicalTrials.gov processed this record on September 11, 2014