Inhaled Doxorubicin in Treating Patients With Primary Lung Cancer or Lung Metastases

Phase I and Clinical Pharmacologic Study of Inhaled Doxorubicin in Adults With Advanced Solid Tumors Affecting the Lungs

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the effectiveness of inhaled doxorubicin in treating patients who have primary lung cancer or lung metastases.

Study Overview

• Status: Completed
• Conditions: Lung Cancer; Metastatic Cancer
• Intervention / Treatment: Drug: doxorubicin hydrochloride

Detailed Description

OBJECTIVES:

• Determine the maximum tolerated dose and phase II dose of inhaled doxorubicin administered every 3 weeks in patients with primary lung cancer or cancer metastatic to the lung.
• Determine the toxic effects and pharmacokinetic profile of this regimen in this patient population.
• Examine the relationship between pharmacodynamic parameters and toxic effects of this regimen in these patients.
• Obtain preliminary evidence of therapeutic activity of this regimen in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive inhaled doxorubicin every 3 weeks. Treatment continues for a maximum of 3 courses in the absence of unacceptable toxicity or disease progression. Patients may reenter at a higher dose level after a 3-month waiting period.

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

Patients are followed at 6 weeks.

PROJECTED ACCRUAL: A total of 3-36 patients will be accrued for this study.

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Memorial Sloan-Kettering Cancer Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Arthur G. James Cancer Hospital - Ohio State University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed primary lung cancer or cancer metastatic to the lung that is not potentially curable by standard chemotherapy, radiotherapy, or surgery

  • Bronchoalveolar cell lung cancer allowed
• Lung metastases from soft tissue sarcoma allowed
• No leukemia or lymphoma

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 70-100%

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 4,000/mm^3
• Platelet count at least 160,000/mm^3
• Hemoglobin at least 9 g/dL

Hepatic:

• Bilirubin no greater than 1.0 mg/dL
• AST/ALT less than 1.5 times upper limit of normal

Renal:

• Creatinine no greater than 1.2 mg/dL OR
• Creatinine clearance at least 50 mL/min

Cardiovascular:

• LVEF normal by MUGA scan or echocardiography
• No unstable angina
• No congestive heart failure
• No symptomatic arrhythmias

Pulmonary:

• DLCO at least 65% of normal
• FVC at least 50% predicted
• FEV1 at least 50% predicted
• Resting oxygen saturation at least 90%
• Exercise oxygen saturation at least 85%
• No complete atelectasis
• No asthma

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after study
• No congenital problems (e.g., cleft palate) or other anomalies that would prevent tight fit of mouth seal
• No other concurrent illness that would preclude study therapy

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics
• At least 3 weeks since prior chemotherapy and recovered
• No prior bleomycin or nitrosoureas
• No prior mitomycin greater than 25 mg/m^2
• No prior anthracyclines greater than 450 mg/m^2
• No other concurrent chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics
• At least 3 weeks since prior radiotherapy and recovered

• No prior chest (pulmonary or mediastinal) or thoracic spine radiotherapy

  • Patients with only chest wall or primary breast radiation are eligible
• No concurrent thoracic irradiation

Surgery:

• See Disease Characteristics
• No prior pneumonectomy

Other:

• No daily or as necessary respiratory drugs via inhaler or nebulizer
• No other concurrent experimental drugs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: July 1, 1999
• Primary Completion (Actual): February 1, 2004
• Study Completion (Actual): February 1, 2004

Study Registration Dates

• First Submitted: March 7, 2000
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): June 19, 2013
• Last Update Submitted That Met QC Criteria: June 18, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Keywords: recurrent non-small cell lung cancer; extensive stage small cell lung cancer; recurrent small cell lung cancer; stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer; bronchoalveolar cell lung cancer; lung metastases
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Doxorubicin; Liposomal doxorubicin
• Other Study ID Numbers: 99-049; CDR0000067614 (Registry Identifier: PDQ (Physician Data Query)); BMI-98-DOX-001; NCI-G00-1696