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

Brief Title

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

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

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).
    

Study Phase

Phase 3

Study Type

Interventional

Primary Outcome

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.

Secondary Outcome

 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

Condition

Carcinoma in Situ

Intervention

VALSTAR - Maintenance Therapy

Study Arms / Comparison Groups

 Maintenance therapy

Description:  Chemotherapeutic: EN3329-301 (VALSTAR)

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

1

Start Date

May 2011

Completion Date

January 2012

Primary Completion Date

January 2012

Eligibility 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
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Philippe E Spiess, MD, MS, FACS, FRCS(C), , 

Location Countries

United States

Location Countries

United States

NCT ID

NCT01310803

Organization ID

EN3329-301

Responsible Party

Sponsor

Study Sponsor

Endo Pharmaceuticals

Study Sponsor

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

Verification Date

September 2017