Multi-center Study to Evaluate the Efficacy and Safety of Maintenance Therapy With Valrubicin Versus no Maintenance, in Subjects Treated With Valrubicin Induction for Carcinoma in Situ (CIS) of the Bladder

• Sponsor: Endo Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01310803
• Collaborator: (none)
• Enrollment: 1
• Locations: 6
• Arms: 2
• Duration (Months): 8
• Patients Per Site: 0.2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This is a Phase 3b open-label, randomized, parallel-arm, multicenter study to evaluate the efficacy and safety of 10 monthly intravesical administrations of maintenance therapy with valrubicin following induction with valrubicin as compared to induction with valrubicin only in subjects with CIS of the bladder. The randomization will be 1:1 and subjects will be stratified by tumor type (CIS plus papillary disease vs. CIS only) and time from last bacillus Calmette-Guerin (BCG) failure (>1 year vs. <1 year).

Condition or Disease	Intervention/Treatment	Phase
Carcinoma in Situ; Transitional Cell Carcinoma; Non-muscle Invasive Bladder Cancer	Drug: VALSTAR - Maintenance Therapy; Other: No Maintenance treatment ( Standard of Care)	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A PHASE 3B, RANDOMIZED, OPEN-LABEL, MULTI-CENTER STUDY TO EVALUATE THE EFFICACY AND SAFETY OF MAINTENANCE THERAPY WITH VALRUBICIN VERSUS NO MAINTENANCE, IN SUBJECTS TREATED WITH VALRUBICIN INDUCTION FOR CARCINOMA IN SITU (CIS) OF THE BLADDER
• Study Start Date: May 1, 2011
• Actual Primary Completion Date: Jan 1, 2012
• Actual Study Completion Date: Jan 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Maintenance therapy Chemotherapeutic: EN3329-301 (VALSTAR)	Drug: VALSTAR - Maintenance Therapy; Treatment phase - 10 monthly intravesical installations starting 10 to 12 weeks after the beginning of induction. Follow-up phase; Other Names: VALSTAR
Other: No Maintenance (Standard of care) Subjects randomized to No Maintenance (Standard of Care) will not receive any additional intravesical therapy	Other: No Maintenance treatment ( Standard of Care); Subjects randomized to No Maintenance (Standard of Care) will not receive any additional intravesical therapy

Outcome Measures

Primary Outcome Measures

1. To Evaluate the Efficacy of Maintenance Therapy With Valrubicin After Induction With Valrubicin, as Compared to Induction With Valrubicin Only in Subjects With CIS of the Bladder. [2 years]

   time interval from randomization to an event. An event is defined as tumor recurrence (any stage or grade), tumor progression to muscle-invasive bladder cancer (MIBC), metastatic bladder cancer or death from any cause, whichever occurs first. Tumor recurrence or progression must be documented by biopsy/transurethral resection of bladder tumor (TURBT).

Secondary Outcome Measures

1. To Evaluate the Safety and Tolerability of Maintenance Therapy With Valrubicin After Induction With Valrubicin, as Compared to Induction With Valrubicin Only in Subjects With CIS of the Bladder [2 years]

   The occurrence of serious adverse events (SAEs), occurrence of local adverse reactions (LARs), results of vital signs, physical exams and laboratory test, and study discontinuation due to inability to complete valrubicin instillations

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Is 18 years of age and older at time of consent signing

2. Have histologically confirmed diagnosis of CIS of the bladder and received valrubicin induction therapy per the labeled indication.

3. Is disease-free following induction with intravesical valrubicin

• Disease-free is defined as negative biopsy 10 to 12 weeks after the initiation of valrubicin induction

• Valrubicin induction is defined as having received at least 3 of 6 weekly instillations

1. Is available for the duration of the study including follow-up (minimum 12 months from randomization)

2. Have an Eastern Cooperative Oncology Group (ECOG) performance status grade of 2 or less

3. Have no evidence of urothelial carcinoma involving the upper urinary tract or prostatic urethra (confirmed by extravesical work up, which may include radiological imaging and/or biopsy) within 6 months prior to randomization

4. Subjects (male and female) of child-bearing potential (including female subjects who are post-menopausal for less than 1 year) must be willing to practice abstinence or effective contraception (as defined by the investigator) during the study and be willing and able to continue contraception for 30 days after their last dose of study treatment

5. Is able to understand and give written informed consent

Exclusion Criteria:

1. Have current or previous history of muscle-invasive bladder cancer (MIBC)

2. Current or previous history of lymph node positive and/or metastatic bladder cancer

3. Have current evidence of pure squamous cell carcinoma, pure adenocarcinoma or pure undifferentiated carcinoma of the bladder

4. Is currently receiving systemic anti-cancer therapy (cytotoxic/cytostatic, immunotherapy or radiation)

5. Received treatment with an investigational agent within 30 days or 5 half-lives prior to randomization, whichever is longer

6. Received treatment with an intravesical chemotherapeutic agent (other than valrubicin or a single administration of mitomycin C post-transurethral resection of bladder tumor [TURBT]) within 3 months prior to randomization

7. Received treatment with valrubicin other than induction within 3 months prior to randomization

8. Have contraindication to valrubicin

• Known hypersensitivity to anthracyclines or polyoxyl castor oil

• Small bladder capacity, i.e. unable to tolerate a 75 mL instillation

• Concurrent urinary tract infection

1. Absolute neutrophil count (ANC) <1000/µL and hemoglobin <10 g/dL

2. Have active cardiovascular disease such as myocardial infarction within the past 3 months, unstable angina pectoris, congestive heart failure (NYHA Class III or IV) or uncontrolled cardiac arrhythmia

3. Female subjects who are pregnant or lactating

4. Subjects of childbearing potential who are unwilling to practice abstinence or effective contraception (as defined by investigator) during the study and for 30 days after last dose of study treatment

5. Have current or history of documented or suspected malignancy of any organ system (diagnosed, treated or untreated) within the past 5 years (with the exception of adequately treated basal cell or squamous cell carcinoma of the skin and asymptomatic non-metastatic prostate cancer either previously successfully treated or currently under active surveillance or receiving hormone therapy only)

6. Is unable to tolerate intravesical administration or intravesical surgical manipulation (cystoscopy or biopsy) even with premedication

7. Have ongoing clinically significant active infections

8. Have any medical or psychiatric condition which, in the opinion of the investigator, would preclude the participant from adhering to the protocol or completing the trial per protocol

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	BCG Oncology	Phoenix	Arizona	United States	85032
2	The Urology Center of Colorado	Denver	Colorado	United States	80211
3	Urology Associates	Cumberland	Maryland	United States	21502
4	Delaware Valley Urology	Sewell	New Jersey	United States	08080
5	Associated Medical Professionals of New York	Syracuse	New York	United States	13210
6	Urologic Consultants of SE PA	Bala-Cynwyd	Pennsylvania	United States	19004

Sponsors and Collaborators

• Endo Pharmaceuticals

Investigators

• Principal Investigator: Philippe E Spiess, MD, MS, FACS, FRCS(C), H. Lee Moffitt Cancer Center and Research Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Endo Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01310803
• Other Study ID Numbers: EN3329-301
• First Posted: Mar 9, 2011
• Last Update Posted: Oct 5, 2017
• Last Verified: Sep 1, 2017

• Keywords provided by Endo Pharmaceuticals: Urinary Bladder Neoplasms; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urinary Bladder Diseases; Urologic Diseases; TURBT; Valstar
• Additional relevant MeSH terms: Carcinoma; Carcinoma in Situ; Carcinoma, Transitional Cell; Valrubicin

Study Results

Participant Flow

Arm/Group Title	Maintenance Therapy	No Maintenance (Standard of Care)
Arm/Group Description	Chemotherapeutic: EN3329-301 (VALSTAR) VALSTAR - Maintenance Therapy: Treatment phase - 10 monthly intravesical installations starting 10 to 12 weeks after the beginning of induction. Follow-up phase	Subjects randomized to No Maintenance (Standard of Care) will not receive any additional intravesical therapy No Maintenance treatment ( Standard of Care): Subjects randomized to No Maintenance (Standard of Care) will not receive any additional intravesical therapy
Period Title: Overall Study
STARTED	1	0
COMPLETED	0	0
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Maintenance Therapy	No Maintenance (Standard of Care)	Total
Arm/Group Description	Chemotherapeutic: EN3329-301 (VALSTAR) VALSTAR - Maintenance Therapy: Treatment phase - 10 monthly intravesical installations starting 10 to 12 weeks after the beginning of induction. Follow-up phase	Subjects randomized to No Maintenance (Standard of Care) will not receive any additional intravesical therapy No Maintenance treatment ( Standard of Care): Subjects randomized to No Maintenance (Standard of Care) will not receive any additional intravesical therapy	Total of all reporting groups
Overall Participants	1	0	1
Age (Count of Participants)
<=18 years	0 0%	0 NaN
Between 18 and 65 years	0 0%	0 NaN
>=65 years	1 100%	1 Infinity
Sex: Female, Male (Count of Participants)
Female	0 0%	0 NaN
Male	1 100%	1 Infinity
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 NaN
Not Hispanic or Latino	1 100%	1 Infinity
Unknown or Not Reported	0 0%	0 NaN
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 NaN
Asian	0 0%	0 NaN
Native Hawaiian or Other Pacific Islander	0 0%	0 NaN
Black or African American	0 0%	0 NaN
White	1 100%	1 Infinity
More than one race	0 0%	0 NaN
Unknown or Not Reported	0 0%	0 NaN

Outcome Measures

1. Primary Outcome

Title	To Evaluate the Efficacy of Maintenance Therapy With Valrubicin After Induction With Valrubicin, as Compared to Induction With Valrubicin Only in Subjects With CIS of the Bladder.
Description	time interval from randomization to an event. An event is defined as tumor recurrence (any stage or grade), tumor progression to muscle-invasive bladder cancer (MIBC), metastatic bladder cancer or death from any cause, whichever occurs first. Tumor recurrence or progression must be documented by biopsy/transurethral resection of bladder tumor (TURBT).
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

No analysis completed due to limited enrollment (1 subject) prior to study termination.

Arm/Group Title	Maintenance Therapy	No Maintenance (Standard of Care)
Arm/Group Description	Chemotherapeutic: EN3329-301 (VALSTAR) VALSTAR - Maintenance Therapy: Treatment phase - 10 monthly intravesical installations starting 10 to 12 weeks after the beginning of induction. Follow-up phase	Subjects randomized to No Maintenance (Standard of Care) will not receive any additional intravesical therapy No Maintenance treatment ( Standard of Care): Subjects randomized to No Maintenance (Standard of Care) will not receive any additional intravesical therapy
Measure Participants	0	0

2. Secondary Outcome

Title	To Evaluate the Safety and Tolerability of Maintenance Therapy With Valrubicin After Induction With Valrubicin, as Compared to Induction With Valrubicin Only in Subjects With CIS of the Bladder
Description	The occurrence of serious adverse events (SAEs), occurrence of local adverse reactions (LARs), results of vital signs, physical exams and laboratory test, and study discontinuation due to inability to complete valrubicin instillations
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

No analysis completed due to limited enrollment (1 subject) prior to study termination.

Arm/Group Title	Maintenance Therapy	No Maintenance (Standard of Care)
Arm/Group Description	Chemotherapeutic: EN3329-301 (VALSTAR) VALSTAR - Maintenance Therapy: Treatment phase - 10 monthly intravesical installations starting 10 to 12 weeks after the beginning of induction. Follow-up phase	Subjects randomized to No Maintenance (Standard of Care) will not receive any additional intravesical therapy No Maintenance treatment ( Standard of Care): Subjects randomized to No Maintenance (Standard of Care) will not receive any additional intravesical therapy
Measure Participants	0	0

Adverse Events

Arm/Group Title	Maintenance Therapy		No Maintenance (Standard of Care)
Arm/Group Description	Chemotherapeutic: EN3329-301 (VALSTAR) VALSTAR - Maintenance Therapy: Treatment phase - 10 monthly intravesical installations starting 10 to 12 weeks after the beginning of induction. Follow-up phase		Subjects randomized to No Maintenance (Standard of Care) will not receive any additional intravesical therapy No Maintenance treatment ( Standard of Care): Subjects randomized to No Maintenance (Standard of Care) will not receive any additional intravesical therapy
All Cause Mortality
	Maintenance Therapy		No Maintenance (Standard of Care)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Maintenance Therapy		No Maintenance (Standard of Care)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Maintenance Therapy		No Maintenance (Standard of Care)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/0 (NaN)

Limitations/Caveats

This study was terminated early. Only one subject was enrolled. No study results were generated.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Institution and/or Principal Investigator shall not publish or present information related to the Study without prior written permission of Sponsor. Sponsor may withhold permission if a publication or presentation is in violation of other agreements, is not consistent with academic standards, is false or misleading, or is for commercial purposes.