Lenalidomide and GM-CSF in Treating Patients With Prostate Cancer

NCT ID: NCT00939510

Last Updated: 2013-01-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-07-31
• Study Completion Date: 2012-12-31

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.

Conditions

Prostate Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Lenalidomide (RevlimidTM ) and GM-CSF

Group Type: EXPERIMENTAL

sargramostim

Intervention Type: BIOLOGICAL

All patients will receive GM-CSF at a dose of 250 mcg subcutaneously on Mondays, Wednesdays and Fridays every week. No dose escalation or de-escalations will be made to GM-CSF.

lenalidomide

Intervention Type: DRUG

Lenalidomide will be administered at 25 mg/day orally on days 1-21 of a 28-day cycle. Initially 6 patients will be entered at the 25 mg/day level. If 0 or 1 patients have a dose limiting toxicity, then the 25 mg lenalidomide + GM-CSF 250 mcg subcutaneously on Mondays, Wednesdays and Fridays every week will be accepted as the phase II dose.

laboratory biomarker analysis

Intervention Type: OTHER

Prior to the initiation of each cycle of therapy for the first 3 cycles, and at discontinuation from study blood will be collected for assessments of a prostate cancer specific immune response.

Interventions

sargramostim

All patients will receive GM-CSF at a dose of 250 mcg subcutaneously on Mondays, Wednesdays and Fridays every week. No dose escalation or de-escalations will be made to GM-CSF.

Intervention Type: BIOLOGICAL

lenalidomide

Lenalidomide will be administered at 25 mg/day orally on days 1-21 of a 28-day cycle. Initially 6 patients will be entered at the 25 mg/day level. If 0 or 1 patients have a dose limiting toxicity, then the 25 mg lenalidomide + GM-CSF 250 mcg subcutaneously on Mondays, Wednesdays and Fridays every week will be accepted as the phase II dose.

Intervention Type: DRUG

laboratory biomarker analysis

Prior to the initiation of each cycle of therapy for the first 3 cycles, and at discontinuation from study blood will be collected for assessments of a prostate cancer specific immune response.

Intervention Type: OTHER

Other Intervention Names

GM-CSF

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Robert Dreicer MD

OTHER

Sponsor Role: lead

Responsible Party

Robert Dreicer MD

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Robert Dreicer, MD, FACP

Role: PRINCIPAL_INVESTIGATOR

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Locations

Cleveland Clinic Taussig Institute, Case Comprehensive Cancer Center

Cleveland, Ohio, United States

Countries

United States

Other Identifiers

P30CA043703

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB# 8121

Identifier Type: OTHER

Identifier Source: secondary_id

RV-PCA-PI-059

Identifier Type: -

Identifier Source: secondary_id

CASE3805

Identifier Type: -

Identifier Source: org_study_id