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

Prostate Cancer Clinical Trial

Official title:

A Randomized Phase II Study of Intermittent Chemotherapy or Intermittent Chemotherapy With Maintenance GM-CSF in Patients With Previously Untreated Hormone Refractory Prostate Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00488982
• Other study ID #: 055511
• Secondary ID: NCI-2011-01269
• Status: Completed
• Phase: Phase 2
• Start date: April 2007
• Est. completion date: May 2014

Study information

• Verified date: October 2019
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 125
• Est. completion date: May 2014
• Est. primary completion date: March 2014
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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)

Inclusion criteria for late enrolling patients:

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

Exclusion criteria for late enrolling patients:

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

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

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

Locations

Country	Name	City	State
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Oregon Health and Science University Cancer Institute	Portland	Oregon
United States	University of California, San Francisco	San Francisco	California
United States	University of Washington	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Francisco	Genzyme, a Sanofi Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall Survival	The Kaplan-Meier product limit method will be used to estimate the median overall survival	Up to 7 years
Secondary	Number of Participants With PSA Response to Successive Series of Chemotherapy	PSA partial response is defined by at least a 50% decline from PSA value from the baseline measurement to 12 weeks of protocol therapy. The decline must be confirmed by a second PSA value obtained 4 or more weeks later For those patients whose PSA have decreased but has not reached response criteria defined above, progressive disease is defined as 25% increase over the nadir PSA value provided that the increase is at least 5ng/mL and is confirmed.	Up to 6 years
Secondary	Cumulative Duration of Time on and Off Docetaxel-based Therapy	Median percentage of time will be calculated to summarize the total duration of chemotherapy and amount of docetaxel/prednisone administered while the patient is on study. The same results will be tabulated for each. For the on-chemotherapy period: will be estimated from the date of starting protocol therapy; if a patient received docetaxel on day 2 of a cycle, he will be considered to have received a full 21 days on therapy. For the off-chemotherapy period: will be calculated from the date of starting the observation or GM-CSF period to the date of resuming chemotherapy	Up to 7 years