Lenalidomide and GM-CSF in Treating Patients With Prostate Cancer

January 24, 2013 updated by: Robert Dreicer MD

Phase I/II Study of Lenalidomide (RevlimidTM ) and GM-CSF in Androgen Independent Prostate Cancer

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.

Study Overview

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.

Study Type

Interventional

Enrollment (Actual)

32

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Taussig Institute, Case Comprehensive Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Lenalidomide (RevlimidTM ) and GM-CSF
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.
Other Names:
  • GM-CSF
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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Patients With a PSA Response
Time Frame: reevaluated for response every eight weeks
Number of patients with a PSA Response defined as a PSA decline greater or equal to 50% compared with baseline value.
reevaluated for response every eight weeks
RECIST-defined Measurable Disease
Time Frame: every 8 weeks and at end of treatment
Patients who have a response of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) by RECIST criteria. To be assigned a status of PR or CR, changes in tumor measurements must be confirmed by repeat assessments that should be performed no less than 4 weeks after the criteria for response are first met. In the case of SD, follow-up measurements must have met the SD criteria at least once after study entry at a minimum interval of 6-8 weeks
every 8 weeks and at end of treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Patients With Statistically Significant Change in Immune Response From Baseline to End of Study
Time Frame: every 28 days for first 3 cycles, end of study
The change in mean T cell immunohistochemical markers and dendritic cells over time will be evaluated using analysis of variance methods for repeated measures with additional main factors included in the analysis for subset comparisons. The pattern of immune response will be evaluated based upon overall clinical response using these same techniques.
every 28 days for first 3 cycles, end of study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Robert Dreicer, MD, FACP, Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2005

Primary Completion (Actual)

October 1, 2009

Study Completion (Actual)

December 1, 2012

Study Registration Dates

First Submitted

July 14, 2009

First Submitted That Met QC Criteria

July 14, 2009

First Posted (Estimate)

July 15, 2009

Study Record Updates

Last Update Posted (Estimate)

January 31, 2013

Last Update Submitted That Met QC Criteria

January 24, 2013

Last Verified

January 1, 2013

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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