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Oral Lenalidomide and Intravesical BCG for Therapy of Bladder Cancer

Primary Purpose

Bladder Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Bacille Calmette-Guerrin (BCG)
Lenalidomide
Sponsored by
H. Lee Moffitt Cancer Center and Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Bladder Cancer focused on measuring non-muscle-invasive, transitional cell, oral lenalidomide, intravesical

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria - Either control group or combination treatment:

  • Understand and voluntarily sign an informed consent form
  • Able to adhere to the study visit schedule and other protocol requirements
  • Ta high grade, T1 high grade or Tis transitional cell bladder cancer, s/p transurethral resection of bladder tumor (TURBT) with no remaining resectable disease
  • Adequate cardio-pulmonary function (</= Class II ) as defined by New York Heart Association Classification, at the time of screening, and no history of myocardial infarction or heart failure within 6 months of start
  • Laboratory test results within these ranges:

    • Absolute neutrophil count ≥ 1500/mm³
    • Platelet count ≥ 75,000
    • Serum creatinine for which computed creatinine clearance is ≥ 30 ml/min, or directly measured creatinine clearance ≥ 30 ml/min
    • Total bilirubin ≤ 1.5 mg/dL
    • Aspartate transaminase (AST) [serum glutamic oxaloacetic transaminase (SGOT)] and Alanine transaminase (ALT) [serum glutamate pyruvic transaminase (SGPT)] ≤ 2 x upper limit of normal (ULN)
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2

Inclusion Criteria - Combination treatment:

  • Prior BCG treatment for non-muscle invasive transitional cell carcinoma (TCC) last administered < 2 years for Ta high-grade, T1 high grade, Cis, or combination thereof
  • Must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®
  • Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy.
  • Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to aspirin may use warfarin or low molecular weight heparin.

Exclusion Criteria:

  • Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the participant from providing informed consent
  • Pregnant or breast feeding (lactating females must agree not to breast feed while taking lenalidomide)
  • Any condition, including the presence of laboratory abnormalities, which places the patient at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
  • Use of any other experimental drug or therapy within 28 days of baseline
  • Known hypersensitivity to thalidomide
  • Known hypersensitivity to BCG or tuberculosis vaccination
  • The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs
  • Any prior use of lenalidomide
  • Concurrent use of other anti-cancer agents or treatments.
  • Known presence of autoimmune disease or immune deficit or chronic disease such as HIV, infectious hepatitis (type B or C), or tuberculosis
  • T2+, or N1+, or M+ disease
  • Ta or T1 low grade disease only
  • Concurrent use of chronic oral steroids, for any indication
  • Recent history of deep venous thrombosis currently receiving anticoagulation therapy, with the clot event being in the last 6 months
  • Diagnosis of any prior malignancies for the last 5 years with exception of definitively treated basal cell, squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix or breast
  • Life expectancy less than 1 year, by treating physician estimate
  • Known exposure to person with active tuberculosis within 48 hours of starting treatment

Sites / Locations

  • H. Lee Moffitt Cancer Center and Research Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

A: Combination Arm

B: Control Arm

Arm Description

Bacille Calmette-Guerrin (BCG) and lenalidomide. Participants were assigned to receive BCG or BCG and lenalidomide based on their cancer. This group received BCG + lenalidomide)

Bacille Calmette-Guerrin (BCG) only. Participants were assigned to receive BCG or BCG and lenalidomide based on their cancer. This group was not eligible to receive the combination of BCG + lenalidomide.

Outcomes

Primary Outcome Measures

Arm A: Progression Free Survival (PFS)
The 1-year progression free/ recurrence free/ bladder-intact survival was tabulated for the experimental arm for a median follow-up period of 369 days. The progression free/ recurrence free/ bladder-intact survival is defined as the time from start of study treatment to first documentation of objective tumor progression, recurrence, bladder resection or irradiation or to death due to any cause, whichever comes first. PFS data was not collected for participants in the Arm B: Control because too few participants were enrolled in Arm B to conduct the planned per Arm comparison

Secondary Outcome Measures

Treatment Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
Number of participants with treatment emergent AEs or SAEs per category. SAEs will be specifically labeled as such. Participants were assessed at monthly intervals (corresponding to Revlimid™ refill points for adverse events), classified by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, and these were tabulated.

Full Information

First Posted
June 13, 2011
Last Updated
August 5, 2019
Sponsor
H. Lee Moffitt Cancer Center and Research Institute
Collaborators
Celgene Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT01373294
Brief Title
Oral Lenalidomide and Intravesical BCG for Therapy of Bladder Cancer
Official Title
Immune Modulation by Addition of Oral Lenalidomide to Intravesical BCG (Bacille Calmette-Guerrin) for Therapy of Non-muscle-invasive Transitional Cell Bladder Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
August 2019
Overall Recruitment Status
Completed
Study Start Date
November 30, 2011 (Actual)
Primary Completion Date
January 9, 2015 (Actual)
Study Completion Date
December 10, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
H. Lee Moffitt Cancer Center and Research Institute
Collaborators
Celgene Corporation

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purposes of this study are to: find out whether participants' cancer returns or gets worse while they are taking lenalidomide and Bacille Calmette-Guerrin (BCG); evaluate the safety and tolerability of the combination of lenalidomide and BCG; compare the cancer progression of participants taking lenalidomide and BCG versus participants taking only BCG
Detailed Description
Investigators planned to screen approximately 100 people with bladder cancer who are 18 years of age or older throughout the United States for this study. This is a multi-center study combining two marketed drugs, one of which has not been used previously in people with transitional cell cancer. Lenalidomide (Revlimid®) is a drug that alters the immune system and it may also interfere with the development of tiny blood vessels that help support tumor growth. Therefore, in theory, it may reduce or prevent the growth of cancer cells. Lenalidomide is approved by the U.S. Food and Drug Administration (FDA) for the treatment of specific types of myelodysplastic syndrome (MDS) and in combination with dexamethasone for patients with multiple myeloma (MM) who have received at least 1 prior therapy. MDS and MM are cancers of the blood. Lenalidomide is currently being tested in a variety of cancer conditions. It is not approved by the FDA for use in people with bladder cancer, so in this case it is considered experimental. The other drug used in this study is Bacille Calmette-Guerrin (BCG). BCG is approved by the FDA for use in people with bladder cancer.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bladder Cancer
Keywords
non-muscle-invasive, transitional cell, oral lenalidomide, intravesical

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
17 (Actual)

8. Arms, Groups, and Interventions

Arm Title
A: Combination Arm
Arm Type
Experimental
Arm Description
Bacille Calmette-Guerrin (BCG) and lenalidomide. Participants were assigned to receive BCG or BCG and lenalidomide based on their cancer. This group received BCG + lenalidomide)
Arm Title
B: Control Arm
Arm Type
Active Comparator
Arm Description
Bacille Calmette-Guerrin (BCG) only. Participants were assigned to receive BCG or BCG and lenalidomide based on their cancer. This group was not eligible to receive the combination of BCG + lenalidomide.
Intervention Type
Drug
Intervention Name(s)
Bacille Calmette-Guerrin (BCG)
Other Intervention Name(s)
BCG Vaccine
Intervention Description
Participants will receive BCG instillations once per week for the first 6 weeks. At 3 months and 6 months, participants will receive BCG instillations once per week for three weeks.
Intervention Type
Drug
Intervention Name(s)
Lenalidomide
Other Intervention Name(s)
Revlimid®
Intervention Description
Participants may also receive capsules of lenalidomide 10 mg to swallow once per day for 7 months. The study doctor will tell participants if they will be taking lenalidomide.
Primary Outcome Measure Information:
Title
Arm A: Progression Free Survival (PFS)
Description
The 1-year progression free/ recurrence free/ bladder-intact survival was tabulated for the experimental arm for a median follow-up period of 369 days. The progression free/ recurrence free/ bladder-intact survival is defined as the time from start of study treatment to first documentation of objective tumor progression, recurrence, bladder resection or irradiation or to death due to any cause, whichever comes first. PFS data was not collected for participants in the Arm B: Control because too few participants were enrolled in Arm B to conduct the planned per Arm comparison
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Treatment Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
Description
Number of participants with treatment emergent AEs or SAEs per category. SAEs will be specifically labeled as such. Participants were assessed at monthly intervals (corresponding to Revlimid™ refill points for adverse events), classified by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, and these were tabulated.
Time Frame
Duration of study treatment and follow-up - average of 12 months
Other Pre-specified Outcome Measures:
Title
Effect of Addition of Revlimid on Cytokines
Description
The immunologic impact of the addition of Revlimid™ to BCG for secondary prevention of non-muscle-invasive transitional cell bladder cancer, in terms of a panel of correlative assays. The effect of addition of Revlimid on cytokines associated with generation of immune response and on cytotoxic T lymphocytes and memory phenotype lymphocytes.
Time Frame
Duration of study treatment and follow-up - average of 12 months
Title
Comparison of the Correlative Assay
Description
For comparing the correlative assay results of ever-relapsers vs non-relapsers, the combined data with the monotherapy and combination therapy groups would be applied. The participants would be categorized based on 1-year relapse.
Time Frame
1 year post disease response

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria - Either control group or combination treatment: Understand and voluntarily sign an informed consent form Able to adhere to the study visit schedule and other protocol requirements Ta high grade, T1 high grade or Tis transitional cell bladder cancer, s/p transurethral resection of bladder tumor (TURBT) with no remaining resectable disease Adequate cardio-pulmonary function (</= Class II ) as defined by New York Heart Association Classification, at the time of screening, and no history of myocardial infarction or heart failure within 6 months of start Laboratory test results within these ranges: Absolute neutrophil count ≥ 1500/mm³ Platelet count ≥ 75,000 Serum creatinine for which computed creatinine clearance is ≥ 30 ml/min, or directly measured creatinine clearance ≥ 30 ml/min Total bilirubin ≤ 1.5 mg/dL Aspartate transaminase (AST) [serum glutamic oxaloacetic transaminase (SGOT)] and Alanine transaminase (ALT) [serum glutamate pyruvic transaminase (SGPT)] ≤ 2 x upper limit of normal (ULN) Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2 Inclusion Criteria - Combination treatment: Prior BCG treatment for non-muscle invasive transitional cell carcinoma (TCC) last administered < 2 years for Ta high-grade, T1 high grade, Cis, or combination thereof Must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist® Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to aspirin may use warfarin or low molecular weight heparin. Exclusion Criteria: Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the participant from providing informed consent Pregnant or breast feeding (lactating females must agree not to breast feed while taking lenalidomide) Any condition, including the presence of laboratory abnormalities, which places the patient at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study Use of any other experimental drug or therapy within 28 days of baseline Known hypersensitivity to thalidomide Known hypersensitivity to BCG or tuberculosis vaccination The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs Any prior use of lenalidomide Concurrent use of other anti-cancer agents or treatments. Known presence of autoimmune disease or immune deficit or chronic disease such as HIV, infectious hepatitis (type B or C), or tuberculosis T2+, or N1+, or M+ disease Ta or T1 low grade disease only Concurrent use of chronic oral steroids, for any indication Recent history of deep venous thrombosis currently receiving anticoagulation therapy, with the clot event being in the last 6 months Diagnosis of any prior malignancies for the last 5 years with exception of definitively treated basal cell, squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix or breast Life expectancy less than 1 year, by treating physician estimate Known exposure to person with active tuberculosis within 48 hours of starting treatment
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mayer Fishman, M.D., Ph.D.
Organizational Affiliation
H. Lee Moffitt Cancer Center and Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
H. Lee Moffitt Cancer Center and Research Institute
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States

12. IPD Sharing Statement

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Oral Lenalidomide and Intravesical BCG for Therapy of Bladder Cancer

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