Clinical trial NCT01316874: 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)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Carcinoma in Situ
Bladder Cancer
Keywords: Valrubicin
CIS
AD 32, BCG-refractory CIS
Carcinoma in situ (CIS) previously treated with BCG
Lead sponsor: Endo Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2011-03-16
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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).

Primary outcomes:
measure: 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.
timeFrame: 12 weeks
Secondary outcomes:
measure: To evaluate the qualitative toxicities associated with intravesical therapy using AD 32 (valrubicin).
timeFrame: 6 weeks
measure: To determine the concentration of anthracyclines in the voided urine of patients who chose to participate in a urine recovery study.
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Alabaster
country: United States
facility: Stacy Childs, MD
state: Alabama
city: Phoenix
country: United States
facility: William Bohnert, MD
state: Arizona
city: Scottsdale
country: United States
facility: Scott Swanson, MD
state: Arizona
city: Tucson
country: United States
facility: Bruce Dalkin, MD
state: Arizona
city: Tucson
country: United States
facility: Donald Gleason, MD
state: Arizona
city: La Mesa
country: United States
facility: William Friedel, MD
state: California
city: Newport Beach
country: United States
facility: Stephen Auerbach, MD
state: California
city: San Diego
country: United States
facility: William Moseley, MD
state: California
city: Santa Monica
country: United States
facility: Standley Brosman, MD
state: California
city: Van Nuys
country: United States
facility: Eugene Dula, MD
state: California
city: Daytona Beach
country: United States
facility: B. Thomas Brown, MD
state: Florida
city: Ft. Lauderdale
country: United States
facility: Charles Jackson, MD
state: Florida
city: Miami
country: United States
facility: Marc Soloway, MD
state: Florida
city: Chicago
country: United States
facility: Charles Brendler, MD
state: Illinois
city: Chicago
country: United States
facility: Patrick Guinan, MD
state: Illinois
city: Evanston
country: United States
facility: Jeffrey Ignatoff, MD
state: Illinois
city: Lexington
country: United States
facility: David Wood, MD
state: Kentucky
city: Lexington
country: United States
facility: John Tuttle, MD
state: Kentucky
city: Shreveport
country: United States
facility: Dennis Venable, MD
state: Louisiana
city: Bethasda
country: United States
facility: Harold Frazier, MD
state: Maryland
city: Greenbelt
country: United States
facility: Myron Murdock, MD
state: Maryland
city: Burlington
country: United States
facility: John Libertino
state: Massachusetts
city: Jackson
country: United States
facility: W. Lamar Weems, MD
state: Mississippi
city: Albany
country: United States
facility: Hugh Fisher, MD
state: New York
city: Rochester
country: United States
facility: Michael Blute, MD
state: New York
city: Burlington
country: United States
facility: Michael Wolff, MD
state: North Carolina
city: Durham
country: United States
facility: Cary Robertson, MD
state: North Carolina
city: Cleveland
country: United States
facility: Eric Klein, MD
state: Ohio
city: Portland
country: United States
facility: Bruce Lowe, MD
state: Oregon
city: Pittsburgh
country: United States
facility: Jeffrey Cohen, MD
state: Pennsylvania
city: Providence
country: United States
facility: Jacques Susset, MD
state: Rhode Island
city: Nashville
country: United States
facility: L. Dean Knoll, MD
state: Tennessee
city: Austin
country: United States
facility: Steohen Hardeman, MD
state: Texas
city: Ft. San Houston
country: United States
facility: Ian Thompson, MD
state: Texas
city: Houston
country: United States
facility: Seth Lemer, MD
state: Texas
city: Richmond
country: United States
facility: Aaron Katz, MD
state: Virginia
city: Richmond
country: United States
facility: Gary Katz, MD
state: Virginia
city: Seattle
country: United States
facility: Williams Ellis, MD
state: Washington
city: Milwaukee
country: United States
facility: Richard Boxer, MD
state: Wisconsin
Study officials:
References:
citation: 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.
citation: 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.