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.

Condition	Treatment or Intervention	Phase
Pulmonary Complications unspecified adult solid tumor, protocol specific Quality of Life	Drug: theophylline	Phase III

Further Study Details: 

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.

PROTOCOL 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.

Ages Eligible for Study:  16 Years and above

Criteria

PROTOCOL ENTRY 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

--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

--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

Canada, British Columbia
      BC Cancer Agency, Vancouver,  British Columbia,  V5Z 4E6,  Canada
Canada, Ontario
      Algoma District Medical Group, Sault Sainte Marie,  Ontario,  P6B 1Y5,  Canada
      Kingston Regional Cancer Centre, Kingston,  Ontario,  K7L 5P9,  Canada
Canada, Quebec
      Centre Hospitalier de l'Universite de Montreal, Montreal,  Quebec,  H2W-W1T8,  Canada

Study chairs or principal investigators

Deborah J. Dudgeon,  Study Chair,  National Cancer Institute of Canada   

Study ID Numbers:  CDR0000066786; CAN-NCIC-SC14
Record last reviewed:  August 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003684
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08