Trial Outcomes & Findings for A Phase II Study of PROSTVAC-V (Vaccinia)/TRICOM and PROSTVAC-F (Fowlpox)/TRICOM With GM-CSF in Patients With PSA Progression After Local Therapy for Prostate Cancer (NCT NCT00108732)

Last Updated: 2015-06-30

Results Overview

For patients who achieved a \> 50% decline in PSA, an increase in PSA value by 50% over the nadir, confirmed by a second PSA two weeks later is considered progressive disease. The PSA rise must be at least 5 ng/mL or back to pretreatment baseline, whichever is greater. Changes in PSA below 5 ng/mL will not be considered assessable for progression. For patients whose PSA has not decreased by 50%, an increase in PSA value \> 50% of baseline (on trial) or nadir PSA, whichever is lower, confirmed by a repeat PSA two weeks later is considered progressive disease. The PSA must have risen by at least 5 ng/mL.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

50 participants

Primary outcome timeframe

Assessed at 6 months

Results posted on

2015-06-30

Participant Flow

The study was activated on February 3, 2006 and terminated on December 11, 2007 after reaching its accrual goal. A total of 50 patients were recruited from ECOG member institutions. Patients with biochemical or clinical progression during Step 1 were eligible to receive androgen blockade in Step 2. To date, 31 patients have registered to Step 2.

Participant milestones

Participant milestones
Measure	Vaccinia/Fowlpox/GM-CSF There are two steps in this study. Patients receive vaccine treatment in Step 1. Patients with biochemical or clinical progression during Step 1 were eligible to continue on to androgen blockade in Step 2. This report includes information collected in Step 1 only. Patients receive vaccinia subcutaneously (SC) on day 1 and GM-CSF SC on days 1-4 during cycle 1. Beginning with cycle 2, patients receive fowlpox SC on day 1 and GM-CSF SC on days 1-4. Treatment with fowlpox and GM-CSF repeats every 4 weeks for 2 courses. Beginning in week 13, patients receive fowlpox and GM-CSF as above every 12 weeks in the absence of clinical or biochemical disease progression or unacceptable toxicity. Patients with biochemical or clinical disease progression may start Step II androgen ablation therapy comprising oral bicalutamide once daily for 1 month and goserelin SC once every 4 weeks in addition to fowlpox vaccine and GM-CSF until further progression or a max of 12 months.
Step 1 (Vaccinia/Fowlpox/GM-CSF) STARTED	50
Step 1 (Vaccinia/Fowlpox/GM-CSF) Eligible and Treated	40
Step 1 (Vaccinia/Fowlpox/GM-CSF) COMPLETED	36
Step 1 (Vaccinia/Fowlpox/GM-CSF) NOT COMPLETED	14
Step 2 (Androgen Ablation and Vaccine) STARTED	31
Step 2 (Androgen Ablation and Vaccine) COMPLETED	26
Step 2 (Androgen Ablation and Vaccine) NOT COMPLETED	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Vaccinia/Fowlpox/GM-CSF There are two steps in this study. Patients receive vaccine treatment in Step 1. Patients with biochemical or clinical progression during Step 1 were eligible to continue on to androgen blockade in Step 2. This report includes information collected in Step 1 only. Patients receive vaccinia subcutaneously (SC) on day 1 and GM-CSF SC on days 1-4 during cycle 1. Beginning with cycle 2, patients receive fowlpox SC on day 1 and GM-CSF SC on days 1-4. Treatment with fowlpox and GM-CSF repeats every 4 weeks for 2 courses. Beginning in week 13, patients receive fowlpox and GM-CSF as above every 12 weeks in the absence of clinical or biochemical disease progression or unacceptable toxicity. Patients with biochemical or clinical disease progression may start Step II androgen ablation therapy comprising oral bicalutamide once daily for 1 month and goserelin SC once every 4 weeks in addition to fowlpox vaccine and GM-CSF until further progression or a max of 12 months.
Step 1 (Vaccinia/Fowlpox/GM-CSF) Adverse Event	1
Step 1 (Vaccinia/Fowlpox/GM-CSF) Withdrawal by Subject	2
Step 1 (Vaccinia/Fowlpox/GM-CSF) Ineligible	10
Step 1 (Vaccinia/Fowlpox/GM-CSF) Non-compliance	1
Step 2 (Androgen Ablation and Vaccine) Adverse Event	3
Step 2 (Androgen Ablation and Vaccine) Withdrawal by Subject	1
Step 2 (Androgen Ablation and Vaccine) Other	1

Baseline Characteristics

A Phase II Study of PROSTVAC-V (Vaccinia)/TRICOM and PROSTVAC-F (Fowlpox)/TRICOM With GM-CSF in Patients With PSA Progression After Local Therapy for Prostate Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Vaccinia/Fowlpox/GM-CSF n=40 Participants Patients receive vaccinia subcutaneously (SC) on day 1 and GM-CSF SC on days 1-4 during cycle 1. Beginning with cycle 2, patients receive fowlpox SC on day 1 and GM-CSF SC on days 1-4. Treatment with fowlpox and GM-CSF repeats every 4 weeks for 2 courses. Beginning in week 13, patients receive fowlpox and GM-CSF as above every 12 weeks in the absence of clinical or biochemical disease progression or unacceptable toxicity. Patients with biochemical or clinical disease progression may start androgen ablation therapy comprising oral bicalutamide once daily for 1 month and goserelin SC once every 4 weeks in addition to fowlpox vaccine and GM-CSF until further progression or a max of 12 months.
Age, Continuous	62.5 years n=39 Participants
Sex: Female, Male Female	0 Participants n=39 Participants
Sex: Female, Male Male	40 Participants n=39 Participants

PRIMARY outcome

Timeframe: Assessed at 6 months

Population: Only eligible and treated patients in step I are included in this analysis.

Outcome measures

Outcome measures
Measure	Vaccinia/Fowlpox/GM-CSF n=40 Participants Patients receive vaccinia subcutaneously (SC) on day 1 and GM-CSF SC on days 1-4 during cycle 1. Beginning with cycle 2, patients receive fowlpox SC on day 1 and GM-CSF SC on days 1-4. Treatment with fowlpox and GM-CSF repeats every 4 weeks for 2 courses. Beginning in week 13, patients receive fowlpox and GM-CSF as above every 12 weeks in the absence of clinical or biochemical disease progression or unacceptable toxicity. Patients with biochemical or clinical disease progression may start androgen ablation therapy comprising oral bicalutamide once daily for 1 month and goserelin SC once every 4 weeks in addition to fowlpox vaccine and GM-CSF until further progression or a max of 12 months.
Proportion of Patients Free of PSA Progression at 6 Months (Prior to the Start of Androgen Ablation)	0.625 Proportion of patients Interval 0.483 to 0.753

SECONDARY outcome

Timeframe: Assessed monthly during the first 24 weeks and then every 3 months for a maximum total of 24 months

Population: Only eligible and treated patients in step I are included in this analysis.

PSA response is defined as complete biochemical response or partial response. Complete Response: A PSA \< 0.2 ng/mL confirmed by a repeat PSA one month later is considered a complete biochemical response for patients with prior radical prostatectomy. A PSA \< 1 ng/mL on three separate occasions taken at least one month apart is considered a complete biochemical response in patients with radiation therapy only. Partial Response: A reduction in PSA by \> 50% from baseline, confirmed by repeat PSA 1 month later.

Outcome measures

Outcome measures
Measure	Vaccinia/Fowlpox/GM-CSF n=40 Participants Patients receive vaccinia subcutaneously (SC) on day 1 and GM-CSF SC on days 1-4 during cycle 1. Beginning with cycle 2, patients receive fowlpox SC on day 1 and GM-CSF SC on days 1-4. Treatment with fowlpox and GM-CSF repeats every 4 weeks for 2 courses. Beginning in week 13, patients receive fowlpox and GM-CSF as above every 12 weeks in the absence of clinical or biochemical disease progression or unacceptable toxicity. Patients with biochemical or clinical disease progression may start androgen ablation therapy comprising oral bicalutamide once daily for 1 month and goserelin SC once every 4 weeks in addition to fowlpox vaccine and GM-CSF until further progression or a max of 12 months.
Proportion of Patients With PSA Response	0 Proportion of patients Interval 0.0 to 0.072

SECONDARY outcome

Timeframe: Assessed at day 4 and day 15 of cycle 1

Population: Only 22 patients with both day 4 and day 15 PSA levels available were included in this analysis.

PSA level was assessed on Day 4 and Day 15 of cycle 1, and a comparison between the two measurements was done.

Outcome measures

Outcome measures
Measure	Vaccinia/Fowlpox/GM-CSF n=22 Participants Patients receive vaccinia subcutaneously (SC) on day 1 and GM-CSF SC on days 1-4 during cycle 1. Beginning with cycle 2, patients receive fowlpox SC on day 1 and GM-CSF SC on days 1-4. Treatment with fowlpox and GM-CSF repeats every 4 weeks for 2 courses. Beginning in week 13, patients receive fowlpox and GM-CSF as above every 12 weeks in the absence of clinical or biochemical disease progression or unacceptable toxicity. Patients with biochemical or clinical disease progression may start androgen ablation therapy comprising oral bicalutamide once daily for 1 month and goserelin SC once every 4 weeks in addition to fowlpox vaccine and GM-CSF until further progression or a max of 12 months.
Difference Between Day 4 PSA Level and Day 15 PSA Level	0.45 ng/mL Interval -1.7 to 2.4

SECONDARY outcome

Timeframe: Assessed monthly during the first 24 weeks and then every 3 months for a maximum total of 24 months

Population: Only 31 patients who completed at least 3 months of treatment were included in this analysis.

PSA slopes were assessed by multiple PSA values obtained prior to registration and during treatment. Only patients who completed at least 3 months of treatment were included in this analysis. The PSA slopes were calculated by a piecewise linear model using the three or four PSA values obtained prior to registration and PSA measurements obtained every 4 weeks for the first six months of treatment. Natural log transformed PSA levels were used in this analysis, and the difference between PSA slopes before and after treatment was calculated.

Outcome measures

Outcome measures
Measure	Vaccinia/Fowlpox/GM-CSF n=31 Participants Patients receive vaccinia subcutaneously (SC) on day 1 and GM-CSF SC on days 1-4 during cycle 1. Beginning with cycle 2, patients receive fowlpox SC on day 1 and GM-CSF SC on days 1-4. Treatment with fowlpox and GM-CSF repeats every 4 weeks for 2 courses. Beginning in week 13, patients receive fowlpox and GM-CSF as above every 12 weeks in the absence of clinical or biochemical disease progression or unacceptable toxicity. Patients with biochemical or clinical disease progression may start androgen ablation therapy comprising oral bicalutamide once daily for 1 month and goserelin SC once every 4 weeks in addition to fowlpox vaccine and GM-CSF until further progression or a max of 12 months.
The Difference Between PSA Slopes Before and After Treatment	-0.04 log PSA/month Interval -0.3 to 0.18

Adverse Events

Vaccinia/Fowlpox/GM-CSF

Serious events: 2 serious events

Other events: 44 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Vaccinia/Fowlpox/GM-CSF n=50 participants at risk Patients receive vaccinia subcutaneously (SC) on day 1 and GM-CSF SC on days 1-4 during cycle 1. Beginning with cycle 2, patients receive fowlpox SC on day 1 and GM-CSF SC on days 1-4. Treatment with fowlpox and GM-CSF repeats every 4 weeks for 2 courses. Beginning in week 13, patients receive fowlpox and GM-CSF as above every 12 weeks in the absence of clinical or biochemical disease progression or unacceptable toxicity. Patients with biochemical or clinical disease progression may start androgen ablation therapy comprising oral bicalutamide once daily for 1 month and goserelin SC once every 4 weeks in addition to fowlpox vaccine and GM-CSF until further progression or a max of 12 months.
General disorders Fever w/o neutropenia	2.0% 1/50 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment.
Musculoskeletal and connective tissue disorders Joint effusion	2.0% 1/50 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment.
Musculoskeletal and connective tissue disorders Muscle pain	2.0% 1/50 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment.

Other adverse events

Other adverse events
Measure	Vaccinia/Fowlpox/GM-CSF n=50 participants at risk Patients receive vaccinia subcutaneously (SC) on day 1 and GM-CSF SC on days 1-4 during cycle 1. Beginning with cycle 2, patients receive fowlpox SC on day 1 and GM-CSF SC on days 1-4. Treatment with fowlpox and GM-CSF repeats every 4 weeks for 2 courses. Beginning in week 13, patients receive fowlpox and GM-CSF as above every 12 weeks in the absence of clinical or biochemical disease progression or unacceptable toxicity. Patients with biochemical or clinical disease progression may start androgen ablation therapy comprising oral bicalutamide once daily for 1 month and goserelin SC once every 4 weeks in addition to fowlpox vaccine and GM-CSF until further progression or a max of 12 months.
Blood and lymphatic system disorders Anemia	8.0% 4/50 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment.
General disorders Fatigue	40.0% 20/50 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment.
General disorders Fever w/o neutropenia	28.0% 14/50 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment.
General disorders Rigors/chills	14.0% 7/50 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment.
General disorders Injection site reaction	56.0% 28/50 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment.
Vascular disorders Hot flashes	6.0% 3/50 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Anorexia	6.0% 3/50 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment.
Investigations Bilirubin increased	6.0% 3/50 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Hyperglycemia	12.0% 6/50 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment.
Musculoskeletal and connective tissue disorders Joint pain	6.0% 3/50 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment.
Musculoskeletal and connective tissue disorders Muscle pain	42.0% 21/50 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment.
General disorders Pain-other	18.0% 9/50 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment.

Additional Information

Study Statistician

ECOG Statistical Office

Phone: 617-632-3012

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60