Intravesical AD 32 (Valrubicin) in Patients With Carcinoma in Situ (CIS) of the Bladder Who Have Failed or Have Recurrence Following Treatment With Bacillus Calmette-guerin (BCG) (Bladder Cancer)

Intravesical AD 32 (Valrubicin) in Patients With Carcinoma in Situ (CIS) of the Bladder Who Have Failed or Have Recurrence Following Treatment With Bacillus Calmette-Guerin (BCG)

This is a Phase II/Phase III study of intravesical AD 32 (valrubicin) in patients with carcinoma in situ (CIS) who have been previously treated with intravesical Bacillus Calmette-Guerin (BCG) for CIS and in whom recurrence or failure has occurred after multiple courses of intravesical treatment.

Study Overview

• Status: Completed
• Conditions: Carcinoma in Situ; Bladder Cancer
• Intervention / Treatment: Drug: Valrubicin, 800 mg

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Alabaster, Alabama, United States
      • Stacy Childs, MD
  • Arizona
    • Phoenix, Arizona, United States
      • William Bohnert, MD
    • Scottsdale, Arizona, United States
      • Scott Swanson, MD
    • Tucson, Arizona, United States
      • Bruce Dalkin, MD
    • Tucson, Arizona, United States
      • Donald Gleason, MD
  • California
    • La Mesa, California, United States
      • William Friedel, MD
    • Newport Beach, California, United States
      • Stephen Auerbach, MD
    • San Diego, California, United States
      • William Moseley, MD
    • Santa Monica, California, United States
      • Standley Brosman, MD
    • Van Nuys, California, United States
      • Eugene Dula, MD
  • Florida
    • Daytona Beach, Florida, United States
      • B. Thomas Brown, MD
    • Ft. Lauderdale, Florida, United States
      • Charles Jackson, MD
    • Miami, Florida, United States
      • Marc Soloway, MD
  • Illinois
    • Chicago, Illinois, United States
      • Charles Brendler, MD
    • Chicago, Illinois, United States
      • Patrick Guinan, MD
    • Evanston, Illinois, United States
      • Jeffrey Ignatoff, MD
  • Kentucky
    • Lexington, Kentucky, United States
      • David Wood, MD
    • Lexington, Kentucky, United States
      • John Tuttle, MD
  • Louisiana
    • Shreveport, Louisiana, United States
      • Dennis Venable, MD
  • Maryland
    • Bethasda, Maryland, United States
      • Harold Frazier, MD
    • Greenbelt, Maryland, United States
      • Myron Murdock, MD
  • Massachusetts
    • Burlington, Massachusetts, United States
      • John Libertino
  • Mississippi
    • Jackson, Mississippi, United States
      • W. Lamar Weems, MD
  • New York
    • Albany, New York, United States
      • Hugh Fisher, MD
    • Rochester, New York, United States
      • Michael Blute, MD
  • North Carolina
    • Burlington, North Carolina, United States
      • Michael Wolff, MD
    • Durham, North Carolina, United States
      • Cary Robertson, MD
  • Ohio
    • Cleveland, Ohio, United States
      • Eric Klein, MD
  • Oregon
    • Portland, Oregon, United States
      • Bruce Lowe, MD
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States
      • Jeffrey Cohen, MD
  • Rhode Island
    • Providence, Rhode Island, United States
      • Jacques Susset, MD
  • Tennessee
    • Nashville, Tennessee, United States
      • L. Dean Knoll, MD
  • Texas
    • Austin, Texas, United States
      • Steohen Hardeman, MD
    • Ft. San Houston, Texas, United States
      • Ian Thompson, MD
    • Houston, Texas, United States
      • Seth Lemer, MD
  • Virginia
    • Richmond, Virginia, United States
      • Aaron Katz, MD
    • Richmond, Virginia, United States
      • Gary Katz, MD
  • Washington
    • Seattle, Washington, United States
      • Williams Ellis, MD
  • Wisconsin
    • Milwaukee, Wisconsin, United States
      • Richard Boxer, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion-

1. Patients must have pathologically-proven CIS with no evidence of muscle invasive disease.
2. Patients with concurrent Ta or T1 papillary tumors are eligible provided papillary tumor(s) are resected prior to study treatment. Cystoscopic evaluation and, if indicated, transurethral resection of bladder tumor (TURBT) must be performed within 28 days of study treatment.
3. Patients must have received at least two or more prior courses of intravesical therapy for CIS per the recommended schedules. BCG must have been one of the prior therapies administered. Patients can have either failed BCG therapy or have been successfully treated with BCG, but subsequently found to have recurrence. The standard course of intravesical therapy must include six weekly treatments (allowable range of instillations per course is 4-9).
4. Patients must have a positive urine cytology at baseline (<28 days) prior to the first AD 32 (valrubicin) treatment. Patients with papillary lesions must have a positive cytology following TURBT or have a baseline cytology that was negative or equivocal and histologic confirmation of CIS.
5. Patients must have an ECOG performance status of 0-2 and a life expectancy of at least 6 months.

Exclusion-

1. Patients with urogenital tumors with histology other than transitional cell carcinoma
2. Patients with residual papillary disease at the time of study treatment.
3. Patients with a history of other primary malignancy (other than squamous or basal cell skin cancers) within the last 5 years.
4. Patients with evidence of muscle invasive disease (stage higher than T1).
5. Patients with any previous intravesical treatment with AD 32 (valrubicin).
6. Patients with any intravesical therapy within 28 days prior to first AD 32 (valrubicin) treatment.
7. Patients with a plan to receive other concurrent therapy for treatment of primary treatment tumor during participation in this study.
8. Patients who had received prior systemic or radiation therapy for bladder cancer.
9. Women who were pregnant or lactating. Individuals of reproductive potential could not participate unless agreeing to use an effective contraceptive method for themselves and/or their sexual partners.
10. Patients who, in the investigator's opinion, could not comply with the provisions of the protocol or did not understand the nature of the study.
11. Patients who, in the opinion of the investigator, could not tolerate intravesical administration of approximately 75 mL of fluid or who could not tolerate surgical manipulation (cystoscopy, mapping biopsies, barbotage) due to the presence of concomitant serious illnesses (ie, uncontrolled cardiac or respiratory disorders).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AD32 (valrubicin); 800mg, once weekly for 6 weeks	Drug: Valrubicin, 800 mg; Investigator will be responsible for regulating the use of concomitant medications (systemic and/or topical anticholinergic therapy or topical anesthesia) and other medications.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Assess the efficacy of AD 32 (valrubicin) in patients with CIS of the bladder who previously have been treated with BCG for CIS and in whom recurrence or failure had occurred after multiple courses of intravesical treatment.	12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
To evaluate the qualitative toxicities associated with intravesical therapy using AD 32 (valrubicin).	6 weeks
To determine the concentration of anthracyclines in the voided urine of patients who chose to participate in a urine recovery study.	6 weeks

Collaborators and Investigators

• Sponsor: Endo Pharmaceuticals

Publications and helpful links

General Publications

• Steinberg G, Bahnson R, Brosman S, Middleton R, Wajsman Z, Wehle M. Efficacy and safety of valrubicin for the treatment of Bacillus Calmette-Guerin refractory carcinoma in situ of the bladder. The Valrubicin Study Group. J Urol. 2000 Mar;163(3):761-7. Erratum In: J Urol. 2008 Jan;179(1):386.
• Steinberg GD, Smith ND, Ryder K, Strangman NM, Slater SJ. Factors affecting valrubicin response in patients with bacillus Calmette-Guerin-refractory bladder carcinoma in situ. Postgrad Med. 2011 May;123(3):28-34. doi: 10.3810/pgm.2011.05.2281.

Study record dates

Study Major Dates

• Study Start: November 1, 1993
• Primary Completion (Actual): April 1, 1997
• Study Completion (Actual): April 1, 1997

Study Registration Dates

• First Submitted: March 15, 2011
• First Submitted That Met QC Criteria: March 15, 2011
• First Posted (Estimate): March 16, 2011

Study Record Updates

• Last Update Posted (Estimate): June 12, 2015
• Last Update Submitted That Met QC Criteria: June 10, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: CIS; Valrubicin; AD 32, BCG-refractory CIS; Carcinoma in situ (CIS) previously treated with BCG
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Disease Attributes; Carcinoma in Situ; Carcinoma; Recurrence; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Valrubicin
• Other Study ID Numbers: A9301/A9302