Combination Chemotherapy With or Without Surgery and Chemoradiotherapy in Treating Patients With Malignant Pleural Mesothelioma - Full Text View

Sponsors and Collaborators:	Case Comprehensive Cancer Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00354393

Purpose

RATIONALE: Drugs used in chemotherapy, such as methotrexate, vinorelbine, 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. Cisplatin may also make tumor cells more sensitive to radiation therapy. Giving chemotherapy and radiation therapy after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase II trial is studying how well giving combination chemotherapy with or without surgery and chemoradiotherapy works in treating patients with malignant pleural mesothelioma.

Condition	Intervention	Phase
Malignant Mesothelioma	Drug: cisplatin Drug: methotrexate Drug: vinorelbine ditartrate Procedure: adjuvant therapy Procedure: conventional surgery Procedure: neoadjuvant therapy Radiation: 3-dimensional conformal radiation therapy Radiation: intensity-modulated radiation therapy	Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	Aggressive Multi-Modality Management of Malignant Pleural Mesothelioma

Resource links provided by NLM:

MedlinePlus related topics: Cancer Mesothelioma Radiation Therapy Surgery

Drug Information available for: Methotrexate Cisplatin Vinorelbine Vinorelbine tartrate

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Response to chemotherapy [ Designated as safety issue: No ]

Secondary Outcome Measures:

Tolerability and toxicity [ Designated as safety issue: Yes ]
Relapse free and overall survival [ Designated as safety issue: No ]
Operability and surgical success [ Designated as safety issue: No ]
Quality of life [ Designated as safety issue: No ]

Estimated Enrollment:	36
Study Start Date:	August 2002

Detailed Description:

OBJECTIVES:

Primary

Assess the response to induction combination chemotherapy comprising methotrexate, vinorelbine ditartrate, and cisplatin in patients with previously untreated malignant pleural mesothelioma.

Secondary

Assess the tolerability and toxicity of this regimen in these patients.
Determine relapse-free and overall survival of patients treated with induction combination chemotherapy with or without surgery and hemithoracic radiation.
Assess the impact of induction combination chemotherapy on operability and surgical success.
Evaluate the impact of these treatment regimens on quality of life.

OUTLINE:

Induction chemotherapy: Patients receive MVP chemotherapy comprising cisplatin IV over 30-60 minutes on day 1 and vinorelbine ditartrate IV over 5-10 minutes and methotrexate IV over 5-30 minutes on days 8, 15, and 22.

Treatment repeats every 28 days for 2 courses. Patients with unresectable disease may receive up to 2 additional courses of induction chemotherapy. Patients requiring palliative radiotherapy or who have progressive disease are removed from the study. Patients with resectable disease or sarcomatoid histology and T1-3, N1-2 disease with a complete or partial response to induction chemotherapy proceed to surgery.

Surgery: Patients with extensive disease undergo palliative debulking pleurectomy and decortication and then are taken off study. All other patients undergo a thoracotomy with an extrapleural pneumonectomy and then proceed to chemoradiotherapy.
Chemoradiotherapy: Beginning 6-10 weeks after surgery, patients undergo 3-dimensional conformal or intensity-modulated radiotherapy once daily, 5 days a week, for 6 weeks. Patients also receive cisplatin IV over 30-60 minutes on days 1 and 22. Patients with responding disease proceed to adjuvant chemotherapy.
Adjuvant chemotherapy: Patients receive 2 additional courses of MVP chemotherapy as above.

Quality of life is assessed at baseline, after each course of induction chemotherapy, before surgery, and then every 3 months thereafter.

After completion of study therapy, patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	up to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed malignant pleural mesothelioma
- Amenable to aggressive surgical resection, if deemed resectable
  - Patients with potentially resectable disease must have undergone mediastinoscopy to establish surgical stage
    - Resectable disease is defined as any of the following:
      - Epithelioid, mixed histology, or histology not otherwise specified with clinical stage I-III (T1-3, N0-2, M0) disease
      - Sarcomatoid histology with clinical stage I-III (T1-3, N0) disease
- Intraperitoneal extension, contralateral thoracic extension, or distant metastases are eligible, but considered unresectable
  - Disease considered unresectable by any medical reason or if surgery was declined

PATIENT CHARACTERISTICS:

ECOG performance status 0-1
WBC ≥ 3,000/mm³
Platelet count > 100,000/mm³
Creatinine ≤ 1.7 mg/dL
Alkaline phosphatase < 2 times normal
AST < 2 times normal
Albumin > 3 g/dL
Bilirubin < 2.0 mg/dL
Patients must be available for and compliant with adequate long-term follow-up
Not pregnant
Negative pregnancy test
Fertile patients must use effective contraception
Patients with resectable disease must have adequate pulmonary function to undergo surgery and radiotherapy
No other active malignancies

PRIOR CONCURRENT THERAPY:

No prior surgical resection, radiation therapy, chemotherapy, or immunotherapy for this cancer

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00354393

Locations

United States, Ohio
Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106-5065

Sponsors and Collaborators

Case Comprehensive Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:

David J. Adelstein, MD

Case Comprehensive Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000486304, CASE-CCF-IRB-5179, CASE-CCF-0755
Study First Received:	July 19, 2006
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00354393 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

localized malignant mesothelioma
sarcomatous mesothelioma
advanced malignant mesothelioma
epithelial mesothelioma

Study placed in the following topic categories:

Antimetabolites
Immunologic Factors
Adjuvants, Immunologic
Folate
Vinblastine
Antimitotic Agents
Folinic Acid
Folic Acid Antagonists
Immunosuppressive Agents
Vitamin B9
Folic Acid

Vinorelbine
Cisplatin
Tubulin Modulators
Mesothelioma
Methotrexate
Antirheumatic Agents
Aggression
Antineoplastic Agents, Phytogenic
Adenoma
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Neoplasms, Mesothelial
Antineoplastic Agents
Physiological Effects of Drugs
Vinblastine
Reproductive Control Agents
Therapeutic Uses
Abortifacient Agents
Methotrexate
Dermatologic Agents
Nucleic Acid Synthesis Inhibitors
Neoplasms by Histologic Type

Mitosis Modulators
Enzyme Inhibitors
Antimitotic Agents
Abortifacient Agents, Nonsteroidal
Folic Acid Antagonists
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Vinorelbine
Tubulin Modulators
Mesothelioma
Antirheumatic Agents
Antineoplastic Agents, Phytogenic
Adenoma
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on September 11, 2009