Paclitaxel and Hyperthermic Perfusion in Treating Patients With Lung Cancer or Lung Metastases That Cannot Be Removed By Surgery

NCT ID: NCT00020007

Last Updated: 2015-04-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 1999-12-31

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Heating paclitaxel to several degrees above body temperature and infusing it to the affected area around the tumor may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of paclitaxel given by hyperthermic perfusion in treating patients with lung cancer or lung metastases that cannot be removed by surgery.

Detailed Description

OBJECTIVES:

• Determine the maximum tolerated dose and phase II dose of paclitaxel administered via hyperthermic retrograde isolated lung perfusion in patients with unresectable pulmonary malignancies.
• Determine the nature of the toxic effects of this regimen in this patient population.
• Evaluate the pharmacokinetic profile of this regimen in these patients.
• Determine the relationship between pharmacodynamic parameters and toxic effects of this regimen in these patients.

OUTLINE: This is a dose-escalation study of paclitaxel.

Patients undergo posterolateral thoracotomy or median sternotomy. Patients receive paclitaxel over 90 minutes administered via hyperthermic retrograde isolated lung perfusion. The entire surgery lasts approximately 4 hours.

Cohorts of 3-6 patients receive escalating doses of paclitaxel until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

Patients are followed at 1 and 2 months. Patients with responding disease continue to be followed every 3 months.

PROJECTED ACCRUAL: A maximum of 31 patients will be accrued for this study.

Conditions

Lung Cancer; Metastatic Cancer

Study Design

• Primary Study Purpose: TREATMENT

Interventions

isolated perfusion

Intervention Type: DRUG

paclitaxel

Intervention Type: DRUG

hyperthermia treatment

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed unresectable primary lung cancer or pulmonary metastases that are unresectable on the basis of technical considerations or are sufficiently numerous that recurrent, potentially inoperable disease is highly probable

• Bilateral metastases allowed
• Unresectable bronchoalveolar carcinomas allowed
• Previously treated primary lung cancer allowed
• Disease outside confines of thorax allowed, provided bulk of disease in the chest is clearly the greatest threat to survival and/or extrathoracic disease is controlled
• No potentially treatable pulmonary metastases from lymphomas or germ cell tumors
• No biopsy proven interstitial fibrosis, radiation induced pneumonitis, or evidence of significant pulmonary hypertension by history, radiologic, echocardiographic, or catheterization studies
• No active intracranial or leptomeningeal metastases

• Prior resection or radiotherapy for intracranial metastases allowed if the following criteria are met:

• No active disease on 2 MRIs done one month apart
• No requirement for anticonvulsant medications or steroids
• Adequate pulmonary reserve to tolerate pneumonectomy:

• Oxygen consumption greater than 50% predicted AND
• FEV1 and DLCO greater than 80% predicted OR
• FEV1 or DLCO less than 80% predicted allowed if postoperative FEV1 and DLCO is at least 40% predicted on the basis of split function V/Q scan
• Prior radiotherapy to chest allowed provided 6 months have elapsed since completion of treatment and no history of, nor current evidence of, interstitial lung disease

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-1

Life expectancy:

• More than 3 months

Hematopoietic:

• Platelet count greater than 100,000/mm^3
• Hemoglobin greater than 10 g/dL
• WBC greater than 3,500/mm^3

Hepatic:

• PT/PTT normal
• Bilirubin less than 1.5 times upper limit of normal (ULN)
• AST/ALT less than 1.5 times ULN

Renal:

• Creatinine less than 1.6 mg/dL

Cardiovascular:

• Fixed defects on thallium scanning with ejection fraction greater than 40% allowed
• Reversible or ischemic defects allowed only after cardiology clearance

Pulmonary:

• See Disease Characteristics
• Resting oxygen saturation greater than 90%
• pCO_2 less than 45 mmHg by arterial blood gas

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active infections
• HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• More than 30 days since prior biologic therapy for this malignancy

Chemotherapy:

• More than 30 days since prior chemotherapy for this malignancy
• Prior paclitaxel allowed
• No prior bleomycin, nitrosoureas, or busulfan

Endocrine therapy:

• See Disease Characteristics

Radiotherapy:

• See Disease Characteristics

Surgery:

• See Disease Characteristics
• Prior thoracic surgery allowed

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Principal Investigators

David S. Schrump, MD

Role: STUDY_CHAIR

NCI - Surgery Branch

Locations

Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support

Bethesda, Maryland, United States

NCI - Center for Cancer Research

Bethesda, Maryland, United States

Countries

United States

Other Identifiers

NCI-00-C-0019

Identifier Type: -

Identifier Source: secondary_id

CDR0000067490

Identifier Type: -

Identifier Source: org_study_id

NCT00001939

Identifier Type: -

Identifier Source: nct_alias