Intermittent Chemotherapy With or Without Granulocyte-macrophage Colony-stimulating Factor (GM-CSF) for Metastatic Hormone Refractory Prostate Cancer (HRPC)

NCT ID: NCT00488982

Last Updated: 2019-11-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 125 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-04-30
• Study Completion Date: 2014-05-31

Brief Summary

This is a two-arm, randomized Phase II study of intermittent chemotherapy with and without GM-CSF. All patients will receive six 21-day cycles of docetaxel 75 mg/m2 on Day 2 of each cycle and 5 mg prednisone twice a day on Days 1-21. Following six cycles of chemotherapy, eligible subjects will be randomized to no maintenance therapy or to maintenance GM-CSF therapy. The GM-CSF group dose schedule will be 250 mcg/m2 subcutaneous (SQ) daily Days 15-28 every 28 days. Patients in both groups will continue until disease progression at which time GM-CSF will be discontinued and chemotherapy will again be administered.

Conditions

Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Docetaxel + Observation

Intermittent docetaxel/prednisone with no maintenance therapy: Patients will discontinue docetaxel/prednisone and undergo observation until disease progression at which time they will re-initiate docetaxel/prednisone. Six cycles of docetaxel/prednisone will again be administered before subsequent discontinuation of chemotherapy

Group Type: EXPERIMENTAL

Docetaxel

Intervention Type: DRUG

Docetaxel 75mg/m2 every 21 days

Docetaxel + GM-CSF

Intermittent docetaxel/prednisone with maintenance GM-CSF therapy: Patients will discontinue docetaxel/prednisone and will receive maintenance GM-CSF until disease progression at which time, they will discontinue GM-CSF and resume docetaxel/prednisone. Six cycles of docetaxel/prednisone will again be administered before discontinuation of chemotherapy and GM-CSF therapy is re-initiated. GM-CSF dose/schedule will be as previously described (250 mcg/m2 SQ daily, days 15-28 q28 days)

Group Type: EXPERIMENTAL

Docetaxel and GM-CSF

Intervention Type: DRUG

Docetaxel 75mg/m2 every 21 days and GM-CSF 250mcg/m2 SQ days 15-28

Interventions

Docetaxel

Docetaxel 75mg/m2 every 21 days

Intervention Type: DRUG

Docetaxel and GM-CSF

Docetaxel 75mg/m2 every 21 days and GM-CSF 250mcg/m2 SQ days 15-28

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age over 18 years

2. Histologically documented adenocarcinoma of the prostate

3. Progressive metastatic prostate cancer

4. Castrate levels of testosterone (<50 ng/ml) must be maintained

5. Prior hormonal therapy or medications :

Patients who are receiving an anti-androgen, secondary hormonal therapy (i.e. ketoconazole, aminoglutethimide, megestrol acetate, diethylstilbestrol), 5-alpha reductase inhibitor (i.e. finasteride (Proscar), dutasteride (Avodart)) or herbal prostate medication (i.e. saw palmetto, PC-SPES, PC-PLUS) must discontinue the drug by the date of initiation of chemotherapy on study

6. ≥ 4 weeks since major surgery and fully recovered

7. ≥ 4 weeks since any prior radiation with any toxicity attributable to radiation resolved to ≤grade 1

8. ≥ 8 weeks since the last dose of strontium or samarium

9. Sexually active patients must agree to use adequate contraception

10. Karnofsky Performance Status ≥ 60%

11. Life expectancy >12 weeks

12. Required initial laboratory values Absolute neutrophil count > 1500/ul Platelets > 100,000/ul Hemoglobin > 8.0 g/dl Creatinine ≤ 2.0 X upper limit of normal Bilirubin ≤upper limit of normal (ULN)

aspartate aminotransferase (AST) / alanine aminotransferase (ALT) / alkaline phosphatase: AST AND ALT AND alkaline phosphatase must be within the range allowing for eligibility In determining eligibility, the more abnormal of the 2 values (AST or ALT should be used. An abnormal alkaline phosphatase must be attributed to liver dysfunction and not metastatic bone involvement (i.e elevated gamma-glutamyl transpeptidase (GGTP) or evidence of liver metastases)

1. Age over 18 years

2. Histologically documented adenocarcinoma of the prostate

3. ≤3 cycles of prior docetaxel chemotherapy for metastatic disease permitted prior to enrollment

4. Docetaxel must have been administered on an every 3 week schedule

5. Each docetaxel dose must have been between 60 and 75 mg/m2

6. Castrate levels of testosterone <50 ng/mL

7. Daily use of other steroids (hydrocortisone, dexamethasone) instead of prednisone or no steroids, is permitted up until time of enrollment

8. A Prostate-specific antigen (PSA) level must have been documented within 6 weeks of initiating docetaxel chemotherapy

Exclusion Criteria

1. Prior systemic chemotherapy for prostate cancer, other than q 3-week docetaxel/prednisone. Prior neoadjuvant or adjuvant chemotherapy is permitted if there was no evidence of disease relapse within 12 months of the last dose of chemotherapy.

2. >3 cycles of q3 week docetaxel/prednisone chemotherapy has already been administered to the patient

3. Peripheral neuropathy >grade 1

4. Prior immunotherapy including systemic GM-CSF or vaccines utilizing GM-CSF; prior G-CSF support of chemotherapy-related neutropenia is permitted

5. Prior biologic agents (i.e.,anti-angiogenic agents, anti-Epithelial Growth Factor Receptor (EGFR) inhibitors)≤ 4 weeks prior to registration

6. More than two prior therapies with an investigational agent, completed ≤ 4 weeks prior to enrollment (no prior immunotherapeutics are allowed)

7. Myocardial infarction or significant change in anginal pattern within the last 6 months, symptomatic congestive heart failure (NYHA Class III or higher) or uncontrolled cardiac arrhythmia

8. Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, HIV-positive patients receiving combination anti-retroviral therapy are excluded

9. Patients with a history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80 will be excluded

10. Poorly controlled diabetes (fasting blood glucose >250) despite optimization of medical therapy

1. Prior immunotherapy including systemic GM-CSF or vaccines utilizing GM-CSF; prior G-CSF support for chemotherapy-related neutropenia is permitted

2. Delay of ≥6 weeks between any 2 chemotherapy cycles prior to enrollment on study

3. Cumulative delays ≥8 weeks between chemotherapy cycles prior to enrollment on study

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

Sponsors

Genzyme, a Sanofi Company

INDUSTRY

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Eric Small, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

University of California, San Francisco

San Francisco, California, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Oregon Health and Science University Cancer Institute

Portland, Oregon, United States

University of Washington

Seattle, Washington, United States

Countries

United States

Other Identifiers

NCI-2011-01269

Identifier Type: REGISTRY

Identifier Source: secondary_id

055511

Identifier Type: -

Identifier Source: org_study_id