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

NCT00488982 | Completed Phase 2 Results DMC

• 2 other identifiers: 055511NCI-2011-01269
• Study Type: interventional
• Target: 125
• Locations: 1 country
• Sites: 4

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

Keywords

Metastatic Hormone Refractory Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Time to Progression

  The Kaplan-Meier product limit method with 95% confidence intervals will be used to estimate the median time to disease progression during initial course of randomized treatment

  Up to 7 years

Secondary Outcomes (3)

• Overall Survival

  Up to 7 years

• Number of Participants With PSA Response to Successive Series of Chemotherapy

  Up to 6 years

• Cumulative Duration of Time on and Off Docetaxel-based Therapy

  Up to 7 years

Study Arms (2)

Docetaxel + Observation

EXPERIMENTAL

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

Drug: Docetaxel

Docetaxel + GM-CSF

EXPERIMENTAL

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)

Drug: Docetaxel and GM-CSF

Interventions

Docetaxel DRUG

Docetaxel 75mg/m2 every 21 days

Docetaxel + Observation

Docetaxel and GM-CSF DRUG

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

Docetaxel + GM-CSF

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age over 18 years
• Histologically documented adenocarcinoma of the prostate
• Progressive metastatic prostate cancer
• Castrate levels of testosterone (\<50 ng/ml) must be maintained
• 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
• ≥ 4 weeks since major surgery and fully recovered
• ≥ 4 weeks since any prior radiation with any toxicity attributable to radiation resolved to ≤grade 1
• ≥ 8 weeks since the last dose of strontium or samarium
• Sexually active patients must agree to use adequate contraception
• Karnofsky Performance Status ≥ 60%
• Life expectancy \>12 weeks
• 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)
• Age over 18 years

You may not qualify if:

• 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.
• \>3 cycles of q3 week docetaxel/prednisone chemotherapy has already been administered to the patient
• Peripheral neuropathy \>grade 1
• Prior immunotherapy including systemic GM-CSF or vaccines utilizing GM-CSF; prior G-CSF support of chemotherapy-related neutropenia is permitted
• Prior biologic agents (i.e.,anti-angiogenic agents, anti-Epithelial Growth Factor Receptor (EGFR) inhibitors)≤ 4 weeks prior to registration
• More than two prior therapies with an investigational agent, completed ≤ 4 weeks prior to enrollment (no prior immunotherapeutics are allowed)
• 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
• 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
• Patients with a history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80 will be excluded
• Poorly controlled diabetes (fasting blood glucose \>250) despite optimization of medical therapy
• Prior immunotherapy including systemic GM-CSF or vaccines utilizing GM-CSF; prior G-CSF support for chemotherapy-related neutropenia is permitted
• Delay of ≥6 weeks between any 2 chemotherapy cycles prior to enrollment on study
• Cumulative delays ≥8 weeks between chemotherapy cycles prior to enrollment on study

Sponsors & Collaborators

• University of California, San Francisco: lead
• Genzyme, a Sanofi Company: collaborator

Study Sites (4)

University of California, San Francisco

San Francisco, California, 94115, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Oregon Health and Science University Cancer Institute

Portland, Oregon, 97239, United States

Location

University of Washington

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Docetaxel; Granulocyte-Macrophage Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Dr. Rahul Aggarwal
• Organization: University of California, San Francisco

Rahul.Aggarwal@ucsf.edu

(415) 353-9278

Study Officials

• Eric Small, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2007
• First Posted: June 20, 2007
• Study Start: April 1, 2007
• Primary Completion: March 1, 2014
• Study Completion: May 1, 2014
• Last Updated: November 20, 2019
• Results First Posted: November 20, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)