Clinical trial NCT00939510: Lenalidomide and GM-CSF in Treating Patients With Prostate Cancer
Official title: Phase I/II Study of Lenalidomide (RevlimidTM ) and GM-CSF in Androgen Independent Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Prostate Cancer
Keywords: adenocarcinoma of the prostate
hormone-resistant prostate cancer
recurrent prostate cancer
stage IV prostate cancer
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2009-07-15
Enrollment: 32
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Lenalidomide may stop the growth of prostate cancer by blocking blood flow to the tumor. GM-CSF may stimulate the immune system in different ways and stop tumor cells from growing. Giving lenalidomide together with GM-CSF may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of lenalidomide when given together with GM-CSF and to see how well it works in treating patients with prostate cancer.

Detailed description: OBJECTIVES:

* Establish the safety of a predetermined target dose or, if the target dose is not tolerable, find the maximum tolerated dose of lenalidomide when administered in combination with sargramostim in patients with androgen-independent prostate cancer.
* Evaluate the preliminary efficacy of this regimen to ascertain whether additional study of lenalidomide is warranted in patients with androgen-independent prostate cancer.
* Evaluate the safety of this regimen in these patients.
* Describe the effects of this regimen on serum cytokines (e.g., TNF-α, bFGF, sIL2R, IL-8, and IL-12) and on serum VEGF levels.
* Assess the co-stimulatory effects of this regimen on CD4+, CD8+, CD83, and CD86 cells.

OUTLINE: This is a phase I, dose-escalation study of lenalidomide followed by a phase II study.

Patients receive oral lenalidomide on days 1-21 and sargramostim subcutaneously on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Blood samples are collected periodically for correlative biomarker and immunological laboratory studies.

After completion of study therapy, patients are followed up at 30 days and then every 3 months thereafter.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed adenocarcinoma of the prostate
* Androgen-independent disease

  * Testosterone ≤ 50 ng/mL

    * Is currently receiving luteinizing hormone-releasing hormone agonists as maintenance or has undergone prior orchiectomy for testosterone suppression
* Progressive disease, as defined by ≥ 1 of the following:

  * Clinical or radiographic evidence of metastases that have progressed irrespective of PSA changes
  * Asymptomatic (non-opioid requiring) bone-only metastatic disease with a rising PSA on separate measurements ≥ 1 week apart

    * No symptomatic bone metastases
  * Biochemical progression (PSA-only disease), defined as having an absolute PSA value of ≥ 2.0 ng/mL on 3 separate measurements ≥ 2 weeks apart with a PSA doubling time of ≤ 10 months
* No evidence of CNS (brain or leptomeningeal) metastases or pleural and/or pericardial effusions

PATIENT CHARACTERISTICS:

* ECOG performance status of 0-1
* ANC ≥ 1,500/mm\^3
* Platelet count ≥ 100,000/mm\^3
* Serum creatinine ≤ 2.0 mg/dL
* AST \< 3 times normal
* Bilirubin \< 1.5 mg/dL
* PT and PTT normal
* Calcium normal
* Fertile patients must use effective contraception during and for ≥ 28 days after completion of study therapy
* Agrees to abstain from donating blood, semen, or sperm during and for ≥ 28 days after completion of study therapy
* No pre-existing peripheral neuropathy \> grade 1
* No active unresolved infection
* No known contraindication to lenalidomide or sargramostim
* No other malignancies within the past 5 years, except for curatively treated basal cell or squamous cell carcinoma of the skin or stage Ta transitional cell carcinoma of the bladder

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* No prior chemotherapy for metastatic prostate cancer
* More than 1 year since prior adjuvant and/or neoadjuvant therapy
* More than 4 weeks since prior flutamide (6 weeks for other antiandrogens)
* No prior thalidomide or lenalidomide
* At least 4 weeks since prior surgery or external-beam radiotherapy and recovered
* At least 6 weeks since prior radiopharmaceutical therapy, including samarium-153 or strontium-89, and recovered
* No initiation of bisphosphonate therapy within 1 month before and during study therapy

  * Patients on stable doses of bisphosphonates who show subsequent tumor progression may continue to receive bisphosphonates
* Concurrent daily aspirin for the prevention of thrombotic events required

  * Patients intolerant to aspirin may receive low-dose warfarin as prophylaxis
* No other concurrent investigational agents
* No other concurrent anticancer therapy, including radiotherapy or thalidomide

Primary outcomes:
measure: Number of Patients With a PSA Response
timeFrame: reevaluated for response every eight weeks
measure: RECIST-defined Measurable Disease
timeFrame: every 8 weeks and at end of treatment
Secondary outcomes:
measure: Number of Patients With Statistically Significant Change in Immune Response From Baseline to End of Study
timeFrame: every 28 days for first 3 cycles, end of study
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Institute, Case Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
name: Robert Dreicer, MD, FACP
role: PRINCIPAL_INVESTIGATOR
References: