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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Endo Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01310803
First received: March 4, 2011
Last updated: October 16, 2014
Last verified: October 2014
  Purpose

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 Intervention 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 Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Endo Pharmaceuticals:

Primary Outcome Measures:
  • 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. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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:
  • 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 [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    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


Enrollment: 1
Study Start Date: May 2011
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: VALSTAR
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  4. Is available for the duration of the study including follow-up (minimum 12 months from randomization)
  5. Have an Eastern Cooperative Oncology Group (ECOG) performance status grade of 2 or less
  6. 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
  7. 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
  8. 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
  9. Absolute neutrophil count (ANC) <1000/µL and hemoglobin <10 g/dL
  10. 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
  11. Female subjects who are pregnant or lactating
  12. 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
  13. 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)
  14. Is unable to tolerate intravesical administration or intravesical surgical manipulation (cystoscopy or biopsy) even with premedication
  15. Have ongoing clinically significant active infections
  16. 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
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: NCT01310803

Locations
United States, Arizona
BCG Oncology
Phoenix, Arizona, United States, 85032
United States, Colorado
The Urology Center of Colorado
Denver, Colorado, United States, 80211
United States, Maryland
Urology Associates
Cumberland, Maryland, United States, 21502
United States, New Jersey
Delaware Valley Urology
Sewell, New Jersey, United States, 08080
United States, New York
Associated Medical Professionals of New York
Syracuse, New York, United States, 13210
United States, Pennsylvania
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
  More Information

No publications provided

Responsible Party: Endo Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01310803     History of Changes
Other Study ID Numbers: EN3329-301
Study First Received: March 4, 2011
Results First Received: October 16, 2014
Last Updated: October 16, 2014
Health Authority: United States: Food and Drug Administration

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
Urinary Bladder Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Urinary Bladder Diseases
Urogenital Neoplasms
Urologic Diseases
Urologic Neoplasms
Valrubicin
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on October 23, 2014