Clinical trial NCT01373294: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Bladder Cancer
Keywords: non-muscle-invasive
transitional cell
oral lenalidomide
intravesical
Lead sponsor: H. Lee Moffitt Cancer Center and Research Institute
Sponsor class: OTHER
Collaborators: name: Celgene Corporation
First posted: 2011-06-14
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Arm A: Progression Free Survival (PFS)
timeFrame: 1 year
Secondary outcomes:
measure: Treatment Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
timeFrame: Duration of study treatment and follow-up - average of 12 months
Other outcomes:
measure: Effect of Addition of Revlimid on Cytokines
timeFrame: Duration of study treatment and follow-up - average of 12 months
measure: Comparison of the Correlative Assay
timeFrame: 1 year post disease response
Locations:
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
Study officials:
affiliation: H. Lee Moffitt Cancer Center and Research Institute
name: Mayer Fishman, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: