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Lenalidomide and GM-CSF in Treating Patients With Prostate Cancer

Primary Purpose

Prostate Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
sargramostim
lenalidomide
laboratory biomarker analysis
Sponsored by
Robert Dreicer MD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Prostate Cancer focused on measuring adenocarcinoma of the prostate, hormone-resistant prostate cancer, recurrent prostate cancer, stage IV prostate cancer

Eligibility Criteria

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

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

Sites / Locations

  • Cleveland Clinic Taussig Institute, Case Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Lenalidomide (RevlimidTM ) and GM-CSF

Arm Description

Outcomes

Primary Outcome Measures

Number of Patients With a PSA Response
Number of patients with a PSA Response defined as a PSA decline greater or equal to 50% compared with baseline value.
RECIST-defined Measurable Disease
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

Secondary Outcome Measures

Number of Patients With Statistically Significant Change in Immune Response From Baseline to 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.

Full Information

First Posted
July 14, 2009
Last Updated
January 24, 2013
Sponsor
Robert Dreicer MD
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00939510
Brief Title
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

2. Study Status

Record Verification Date
January 2013
Overall Recruitment Status
Completed
Study Start Date
July 2005 (undefined)
Primary Completion Date
October 2009 (Actual)
Study Completion Date
December 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Robert Dreicer MD
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer
Keywords
adenocarcinoma of the prostate, hormone-resistant prostate cancer, recurrent prostate cancer, stage IV prostate cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
32 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Lenalidomide (RevlimidTM ) and GM-CSF
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
sargramostim
Other Intervention Name(s)
GM-CSF
Intervention Description
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
Drug
Intervention Name(s)
lenalidomide
Intervention Description
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
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of Patients With a PSA Response
Description
Number of patients with a PSA Response defined as a PSA decline greater or equal to 50% compared with baseline value.
Time Frame
reevaluated for response every eight weeks
Title
RECIST-defined Measurable Disease
Description
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
Time Frame
every 8 weeks and at end of treatment
Secondary Outcome Measure Information:
Title
Number of Patients With Statistically Significant Change in Immune Response From Baseline to End of Study
Description
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.
Time Frame
every 28 days for first 3 cycles, end of study

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Dreicer, MD, FACP
Organizational Affiliation
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cleveland Clinic Taussig Institute, Case Comprehensive Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Lenalidomide and GM-CSF in Treating Patients With Prostate Cancer

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