Adenosine Triphosphate in Treating Patients With Advanced Solid Tumors

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)

RATIONALE: Adenosine triphosphate may decrease weight loss and improve muscle strength in patients with advanced solid tumors.

PURPOSE: Phase I trial to study the effectiveness of adenosine triphosphate in controlling loss of weight and loss of muscle mass in patients who have advanced solid tumors.

Study Overview

• Status: Completed
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific; Cachexia
• Intervention / Treatment: Procedure: quality-of-life assessment; Drug: adenosine triphosphate

Detailed Description

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.

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756-0002
      • Norris Cotton Cancer Center

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 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care

Collaborators and Investigators

• Sponsor: Dartmouth-Hitchcock Medical Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Lionel D. Lewis, MD, Norris Cotton Cancer Center

Study record dates

Study Major Dates

• Study Start: October 1, 2000
• Primary Completion (Actual): November 1, 2002

Study Registration Dates

• First Submitted: April 10, 2001
• First Submitted That Met QC Criteria: July 29, 2003
• First Posted (Estimate): July 30, 2003

Study Record Updates

• Last Update Posted (Estimate): March 18, 2013
• Last Update Submitted That Met QC Criteria: March 15, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: unspecified adult solid tumor, protocol specific; cachexia
• Additional Relevant MeSH Terms: Metabolic Diseases; Nutrition Disorders; Body Weight; Body Weight Changes; Emaciation; Weight Loss; Wasting Syndrome; Cachexia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Vasodilator Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Purinergic Agents; Purinergic P1 Receptor Agonists; Purinergic Agonists; Adenosine
• Other Study ID Numbers: CDR0000068522; DMS-0005; ATP-DMS-0005; NCI-G01-1923