A Phase I Study And Pharmacokinetics Of Adenosine 5'- Triphosphate (ATP) When Administered By Intravenous Infusion On A Multiple Weekly Dose Schedule To Patients With Advanced Malignancies (Solid Tumors)
18 Years
N/A
Both
Cachexia, Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
A Phase I Study And Pharmacokinetics Of Adenosine 5'- Triphosphate (ATP) When Administered By Intravenous Infusion On A Multiple Weekly Dose Schedule To Patients With Advanced Malignancies (Solid Tumors)
OBJECTIVES:
- Determine the individualized maximum tolerated dose of adenosine triphosphate in
patients with advanced solid tumors.
- Determine the safety of this regimen in these patients.
- Determine the pharmacokinetics of this regimen in these patients.
- Determine the effect of this regimen on quality of life of these patients.
- Determine the influence of this regimen on cancer cachexia in terms of weight change,
percentage of body fat, voluntary muscle strength, and plasma markers in these
patients.
- Determine the effect of this regimen on tumor burden in these patients.
OUTLINE: This is a dose-escalation study.
Patients receive adenosine triphosphate (ATP) IV over 8 hours on day 0. Treatment repeats
weekly for a total of 8 courses in the absence of disease progression or unacceptable
toxicity.
Each patient receives escalating doses of ATP until the individual maximum tolerated dose
(MTD) is determined. The MTD is defined as the dose preceding that at which the patient
experiences at least grade 3 (at least grade 2 cardiac ischemia or arrhythmia) toxicity.
Weight is measured at baseline and at weeks 1-8, 10, and 13. Percentage of body fat and
skeletal muscle strength is measured at baseline and at weeks 2, 4, 8, 10, and 13.
Quality of life is assessed at baseline and at weeks 2, 4, 8, 10, and 13.
Patients are followed at weeks 10 and 13.
PROJECTED ACCRUAL: A maximum of 13-24 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed advanced solid tumor that is not curable by
conventional therapy
- Brain metastases allowed if adequately controlled with radiotherapy
PATIENT CHARACTERISTICS:
Age:
- Over 18
Performance status:
- Karnofsky 60-100%
Life expectancy:
- At least 12 weeks
Hematopoietic:
- WBC at least 3,500/mm^3
- Absolute neutrophil count at least 2,000/mm^3
- Platelet count at least 100,000/mm^3
Hepatic:
- SGOT and SGPT no greater than 3 times normal
- Bilirubin no greater than 2.0 mg/dL
Renal:
- Creatinine no greater than 1.5 mg/dL
- Creatinine clearance greater than 60 mL/min
- BUN no greater than 25 mg/dL
Cardiovascular:
- Adequate cardiovascular function
- No congestive heart failure (New York Heart Association class III or IV heart
disease)
- No angina pectoris AND/OR
- No significant arrhythmia
- No myocardial infarction within the past 6 months
- No clinically significant ischemic cardiac disease currently under treatment
- No clinically significant conduction system disease in the absence of a pacemaker
(e.g., sick sinus syndrome, or second or third degree atrioventricular block)
Pulmonary:
- Adequate pulmonary function
- No clinical evidence of acute chronic obstructive pulmonary disease
- FEV1 at least 50% predicted
- Arterial oxygen tension at least 90% by pulse oximetry and on breathing room air
- No asthma OR
- No evidence of more than 20% reversibility in FEV1 with albuterol therapy
Other:
- Not pregnant or nursing
- Fertile patients must use effective contraception
- No history of severe adverse reaction to adenosine
- No uncontrolled medical illness
- No average daily pain scores of at least 5 on a simple Visual Analogue Self pain
assessment (0-10) scale
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- Not specified
Chemotherapy:
- At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and
recovered
Endocrine therapy:
- Not specified
Radiotherapy:
- See Disease Characteristics
- At least 3 weeks since prior radiotherapy and recovered
Surgery:
- Not specified
Other:
- At least 30 days since prior investigational therapy
- At least 14 days since prior long-term theophylline, dipyridamole, or
dipyridamole/aspirin therapy
- No concurrent long-term theophylline, dipyridamole, or dipyridamole/aspirin therapy
- No concurrent maintenance anti-anginal drug therapy
Type of Study:
Interventional
Study Design:
Primary Purpose: Supportive Care
Principal Investigator
Lionel D. Lewis, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Norris Cotton Cancer Center
Authority:
United States: Institutional Review Board
Study ID:
CDR0000068522
NCT ID:
NCT00014248
Start Date:
October 2000
Completion Date:
Related Keywords:
- Cachexia
- Unspecified Adult Solid Tumor, Protocol Specific
- unspecified adult solid tumor, protocol specific
- cachexia
- Cachexia
- Neoplasms
Name | Location |
|---|---|
| Norris Cotton Cancer Center | Lebanon, New Hampshire 03756 |
