Theophylline in Treating Cancer Patients With Shortness of Breath

Condition(s) targeted: Pulmonary Complications; Quality of Life; Unspecified Adult Solid Tumor, Protocol Specific

Intervention: theophylline (Drug); quality-of-life assessment (Procedure)

Phase: Phase 3

Status: Active, not recruiting

Sponsored by: National Cancer Institute of Canada

Official(s) and/or principal investigator(s):
Deborah J. Dudgeon, MD, RN, Study Chair, Affiliation: Cancer Research Institute at Queen's University

RATIONALE: Theophylline may help to relieve shortness of breath in patients who have cancer. It is not yet known whether theophylline is more effective than no further treatment for shortness of breath.

PURPOSE: Randomized phase III trial to determine the effectiveness of theophylline in treating shortness of breath in patients who have cancer.

Official title: A Phase III Double-Blind Study of Theophylline Versus Placebo for the Treatment of Dyspnea in Cancer Patients

Study design: Supportive Care, Randomized

Detailed description: OBJECTIVES: I. Determine whether theophylline will improve the dyspnea rating of patients with cancer who are short of breath and have evidence of respiratory muscle weakness. II. Determine whether this drug will improve the ability to perform daily activities in this group of patients. III. Determine whether this drug will improve objective measures of lung function (e. g., FEV-1, FVC) and maximum inspiratory pressure in these patients. IV. Determine whether the serum theophylline level is related to the magnitude of the effect that is observed in this patient population. V. Determine whether this drug will improve a global rating of quality of life in this patient group.

OUTLINE: This is a randomized, double blind, multicenter study. Patients are stratified according to those who can complete a 6 minute walking test versus those who cannot. Patients receive either oral theophylline or placebo once daily for 3 days. In the absence of dose limiting toxicity (DLT), patients receive an increased dose for an additional 4 days. In the presence of DLT, patients receive a decreased dose or treatment is stopped. Following completion of the 7 day study period, patients may be given the option to continue on active drug or placebo for 1 additional month unless toxic side effects develop. Quality of life is assessed on days 1 and 8 and at the end of the additional 1 month period.

PROJECTED ACCRUAL: A total of 60 patients (30 in each arm) will be accrued for this study.

Minimum age: 16 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

DISEASE CHARACTERISTICS: Histologically or cytologically proven diagnosis of cancer FEV-1/FVC at least 80% of predicted OR FEV-1/FVC less than 80% AND improvement in FEV-1

less than 15% after using a bronchodilator Maximum inspiratory pressure no greater than - 50

cm of water Oximetry at least 90% Rating of dyspnea "moderate" or "severe" on verbal rating scale (VRS) of "none, mild, moderate, or severe" to describe "usual breathlessness" when walking over the past 24 hours Score for pain of "none" or "mild" on a VRS of "none, mild, moderate, or severe" for "unusual pain" over the past 24 hours

PATIENT CHARACTERISTICS: Age: 16 and over Performance status: Not specified Life expectancy: Greater than 10 days Hematopoietic: Hemoglobin at least 8. 5 g/dL Hepatic: AST/ALT no greater than 2 times upper limit of normal (ULN) No liver disease Renal: Creatinine no greater than 2 times ULN No kidney disease Cardiovascular: No acute congestive heart failure Greater than 3 months since prior myocardial infarction No coronary artery disease where cardiac stimulation might prove harmful (i. e., no unstable angina) No uncontrolled hypertension Pulmonary: See Disease Characteristics Other: Folstein Mini-Mental Status Exam score of at least 24 Able (i. e., sufficiently fluent) and willing to complete quality of life questionnaire and other assessments in either English or French No history of clinically significant allergy or intolerance to theophylline, aminophylline, or other methylxanthines No active peptic ulcer disease No uncontrolled hyperthyroidism

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: At least 14 days since prior chemotherapy No concurrent chemotherapy Endocrine therapy: At least 2 months since prior initiation of hormonal therapy Hormones as appetite stimulant allowed if received for more than 2 weeks No concurrent oral contraceptives Concurrent steroids allowed if taken for at least 1 week prior to study Concurrent inhaled or oral corticosteroids allowed if taken for at least 1 week prior to study No concurrent initiation of a new hormonal manipulation Radiotherapy: At least 28 days since prior radiotherapy that includes the lung in the treatment field No concurrent radiotherapy that includes the lung in the treatment field Surgery: Not specified Other: No concurrent digitalis glycosides, lithium, coumarin anticoagulants, other xanthines, cimetidine, quinolone antibiotics (e. g, ciprofloxacin and norfloxacin), macrolide antibiotics (e. g., erythromycin), fluvoxamine, and calcium channel blockers Concurrent nebulized or inhaled cromolyn, nedocromil, beta2-agonists, ipratropium, opioids, benzodiazepines, oxygen, and diuretics allowed if dose is stable for more than 1 week prior to study No concurrent paracentesis (i. e., thoracentesis) No concurrent blood transfusion

BC Cancer Agency, Vancouver, British Columbia V5Z 4E6, Canada

Algoma District Medical Group, Sault Sainte Marie, Ontario P6B 1Y5, Canada

Kingston Regional Cancer Centre, Kingston, Ontario K7L 5P9, Canada

Centre Hospitalier de l'Universite de Montreal, Montreal, Quebec H2W-W1T8, Canada

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: March 1998
Last updated: May 23, 2008