GM-CSF and Thalidomide in Treating Patients Undergoing Surgery for High-Risk Prostate Cancer

• ClinicalTrials.gov Identifier: NCT00400517
• Recruitment Status: Completed
• First Posted: November 17, 2006
• Results First Posted: August 28, 2018
• Last Update Posted: August 28, 2018
• Sponsor: The Cleveland Clinic
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): The Cleveland Clinic

Study Description

Brief Summary:

RATIONALE: Biological therapies, such as GM-CSF, may stimulate the immune system in different ways and stop tumor cells from growing. Thalidomide may stop the growth of prostate cancer by blocking blood flow to the tumor. Giving GM-CSF and thalidomide before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This phase II trial is studying how well giving GM-CSF together with thalidomide works in treating patients undergoing surgery for high-risk prostate cancer.

Condition or disease	Intervention/treatment	Phase
Prostate Cancer	Biological: sargramostim; Drug: thalidomide; Procedure: conventional surgery; Procedure: neoadjuvant therapy	Phase 2

Detailed Description:

OBJECTIVES:

• Evaluate the impact of neoadjuvant sargramostim (GM-CSF) and thalidomide on pathologic response (histologic P0, margin positivity, capsular penetration), prostate-specific antigen (PSA) response, and other investigational endpoints in patients with high-risk prostate cancer undergoing prostatectomy.
• Determine the safety and feasibility of GM-CSF and thalidomide.

OUTLINE: This is an open-label study.

Patients receive sargramostim (GM-CSF) subcutaneously on days 1, 3, and 5 and oral thalidomide on days 1-5 or 1-7 in weeks 1-4. Treatment repeats every 4 weeks for 2 courses in the absence of unacceptable toxicity.

Patients undergo radical prostatectomy with bilateral pelvic lymphadenectomy at week 8 or 9.

PROJECTED ACCRUAL: A total of 29 patients will be accrued for this study.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 28 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Neoadjuvant GM-CSF + Thalidomide in High-Risk Patients With Prostate Cancer Undergoing Prostatectomy
• Study Start Date: March 2003
• Actual Primary Completion Date: June 2008
• Actual Study Completion Date: June 2008

Arms and Interventions

Arm

Intervention/treatment

Experimental: GM-CSF Injections and Oral Thalidomide; taught to administer an injection of GM-CSF under your skin (subcutaneous injection) and will administer this medicine to yourself every Monday, Wednesday and Friday for 4 weeks at time. Thalidomide will be taken orally (by mouth) every evening at bed time. You will continue these injections 3 times a week and the daily oral medicine for up to 2 months if the therapy appears to be helping your disease.

Biological: sargramostim; administered subcutaneously, generally well tolerated doses range from 50-500 ug/m2/day; Other Name: GM-CSF; Drug: thalidomide; doses up to 400 mg/day; Other Name: THALOMID; Procedure: conventional surgery; SOC care surgery; Procedure: neoadjuvant therapy; post radical prostatectomy

Outcome Measures

Primary Outcome Measures :

1. Proportion of Patients P0 at Surgery [ Time Frame: 8 weeks ]
   Pathologic Complete Response is defined as complete eradication of tumor.
2. Proportion of Patients With Negative Surgical Margins [ Time Frame: 8 Weeks ]
   Presence or Absence of prostate cancer tissue at the sites of surgical resection. This is done by reviewing the entire specimen resected at the time or Radical Prostatectomy.
3. Prostate-specific Antigen Response [ Time Frame: 8 weeks ]
   Number of subjects that achieved a PSA decline while on therapy. Any PSA decline while on treatment, compared with baseline PSA prior to study entry.
4. Time to Clinical Progression [ Time Frame: 32 months ]
   Time to progression. WIth a median follow up of 32 months (12-51 months), 5 of 26 patients developed biochemical failure.

Eligibility Criteria

• Ages Eligible for Study: up to 120 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the prostate meeting any of the following criteria for high-risk disease:

  • Clinical stage II or III (T2b, T2c, or T3 with any grade or prostate-specific antigen [PSA])
  • Gleason score 7 (4+3 only) or ≥ 8 (any stage or PSA)
  • Serum PSA ≥ 10 ng/dL (any grade or stage)
  • Any stage, PSA, or Gleason score with ≥ 35% chance of biochemical failure at 5 years based on Kattan's nomogram
• No clinical evidence of CNS metastases
• No metastatic disease as demonstrated by radiological exam (CT scan, MRI, bone scan, x-ray) within 8 weeks of study entry
• Appropriate medical candidate for radical prostatectomy

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• Creatinine ≤ 2.0 mg/dL
• Granulocyte count ≥ 1,800/mm³
• Platelet count ≥ 100,000/mm³
• AST < 3 times upper limit of normal
• Bilirubin ≤ 1.5 mg/dL
• Fertile patients must use effective contraception during and for 4 weeks after completion of study treatment
• No active unresolved infection
• No pre-existing peripheral neuropathy > grade 1
• No known HIV positivity
• No other malignancy within the past 5 years except curatively treated basal cell or squamous cell carcinoma of the skin or controlled Ta transitional cell carcinoma of the bladder
• No known contraindication to sargramostim (GM-CSF) or thalidomide

PRIOR CONCURRENT THERAPY:

• No prior radiotherapy to the prostate or pelvis
• No prior chemotherapy or hormonal therapy for prostate cancer
• No parenteral antibiotics within the past 7 days

Contacts and Locations

Locations

United States, Ohio

Cleveland Clinic

Cleveland, Ohio, United States, 44195

Sponsors and Collaborators

The Cleveland Clinic

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Jorge Garcia, MD, FACP; The Cleveland Clinic
• Principal Investigator: Eric Klein, MD; The Cleveland Clinic

More Information

• Responsible Party: The Cleveland Clinic
• ClinicalTrials.gov Identifier: NCT00400517
• Other Study ID Numbers: CASE-CCF-4643; P30CA043703 ( U.S. NIH Grant/Contract ); CASE-CCF-4643 ( Other Identifier: Case Comprehensive Cancer Center ); CELGENE-CASE-CCF-4643 ( Other Identifier: Sponsor ); BRLX-CASE-CCF-4643 ( Other Identifier: Sponsor )
• First Posted: November 17, 2006
• Results First Posted: August 28, 2018
• Last Update Posted: August 28, 2018
• Last Verified: July 2018

Keywords provided by The Cleveland Clinic:

stage III prostate cancer; stage II prostate cancer; adenocarcinoma of the prostate; stage I prostate cancer; stage IV prostate cancer

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Prostatic Diseases; Thalidomide; Sargramostim; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Leprostatic Agents; Anti-Bacterial Agents; Anti-Infective Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Antineoplastic Agents