Study of BCG + Aminophylline Toxicity When Used in the Treatment of Bladder Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Virginia
ClinicalTrials.gov Identifier:
NCT01240824
First received: November 11, 2010
Last updated: April 10, 2014
Last verified: April 2014
  Purpose

The purpose of this study is to evaluate whether a new potential treatment for non invasive bladder cancer is safe and if it leads to side effects such as irregular heart rate, agitation, or burning with urination. Patients who have early stage bladder cancer and will be receiving BCG, a bladder cancer therapy as recommended by a doctor, will be asked to participate in a study where they are given the standard BCG followed by the experimental drug, aminophylline. Although we hope this medicine may one day prove to help bladder cancer patients, at the current time we do not know if it has any benefits at all. We have data in mice that suggest that aminophylline slows the growth of tumors when coupled with BCG.


Condition Intervention Phase
Bladder Cancer
Drug: aminophylline
Phase 0

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: A Phase I Trial to Determine the Safety, Tolerability and Maximum Tolerated Intravesical Dose of Aminophylline With BCG in Patients With Non-invasive Bladder Cancer

Resource links provided by NLM:


Further study details as provided by University of Virginia:

Primary Outcome Measures:
  • Dose limiting toxicity [ Time Frame: Week 6 ] [ Designated as safety issue: Yes ]
    Any cardiac arrythmia or seizure activity, > grade 2 allergic reactions, fever 101.5 for > 48 hours, > grade 1 insomnia, > grade 1 involuntary movements, > grade 2 nausea / vomiting, > grade 2 bladder spasms, dysuria or pelvic pain.


Enrollment: 3
Study Start Date: July 2010
Study Completion Date: February 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BCG + aminophylline
Bacillus Calmette-Guerin (BCG) plus one of three escalating doses of aminophylline administered intravesically.
Drug: aminophylline
One of three escalating doses of aminophylline (3 mg/kg, 6 mg/kg and 9 mg/kg) administered intravesically

Detailed Description:

Before using the combination of BCG and aminophylline clinically, we need to first determine if aminophylline is safe, when placed directly into the bladder of patients who have bladder cancer. We will give it along with BCG (Bacillus Calmette-Guerin) - a medication put into the bladder through a catheter tube to treat bladder cancer.

We also would like to determine the maximum dose of aminophylline that can be safely given and how the drug is absorbed and used by the body as well as document side effects when aminophylline is given in the bladder.

This is a study about aminophylline instilled into the bladder. Aminophylline has not been proven to be safe or a helpful treatment for bladder cancer. It is considered an experimental drug as used in this protocol for bladder cancer. Aminophylline has not been given to anyone who has bladder cancer. Aminophylline is approved by the U.S. Food and Drug Administration (FDA ) to give directly into the bloodstream for the treatment of asthma. We intend to use it at doses much lower than that used for asthma.

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female > 40 years of age because in patients younger than that the natural history is different.
  2. Histologically proven bladder cancer that is NOT muscle invasive (Ta or T1)
  3. Transurethral resection of Bladder Tumor (TURBT) at least 2 weeks prior to first instillation
  4. ECOG performance status of 0 or 1.
  5. Informed consent obtained from patient before enrollment.
  6. English is primary language
  7. Patients undergoing initial 6 week BCG therapy (BCG naïve)
  8. Patients undergoing 3 week BCG maintenance therapy.

Exclusion Criteria:

  1. Hypersensitivity reaction or contraindication to aminophylline or theophylline
  2. Pregnancy (confirmed by a serum human chorionic gonadotropin pregnancy test) or breast feeding).
  3. Hepatic insufficiency as defined by an abnormal AST or ALT.
  4. Known arrhythmias or heart failure as defined by class II or greater cardiovascular disease according to the New York Heart Associations functional criteria
  5. Immunocompromised
  6. Seizure disorder.
  7. Current treatment with oral theophylline or any other methylxanthine derivative.
  8. Active urinary tract infection by nitrite positive urine dip or gross hematuria
  9. Reduced dosing of BCG or BCG failures who have experienced bladder cancer recurrrence.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01240824

Locations
United States, Virginia
University of Virginia Urology Department
Charlottesville, Virginia, United States, 22908
Sponsors and Collaborators
University of Virginia
Investigators
Principal Investigator: Tracy L Krupski, M.D. University of Virginia
  More Information

No publications provided

Responsible Party: University of Virginia
ClinicalTrials.gov Identifier: NCT01240824     History of Changes
Other Study ID Numbers: 14585
Study First Received: November 11, 2010
Last Updated: April 10, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Virginia:
bladder cancer
urothelial carcinoma
transitional cell carcinoma bladder
ureter

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Aminophylline
Cardiotonic Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Purinergic P1 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Protective Agents

ClinicalTrials.gov processed this record on July 29, 2014