Trial Outcomes & Findings for A Neoadjuvant Study of Androgen Ablation Combined With Cyclophosphamide and GVAX Vaccine for Localized Prostate Cancer (NCT NCT01696877)

Last Updated: 2019-03-28

Results Overview

CD8+ T cell infiltration (quantified as log\[CD8 density\]) into the prostate from harvested prostate glands in men with localized prostate cancer receiving neoadjuvant Androgen deprivation therapy alone (2 weeks prior to surgery), or cyclophosphamide and GVAX followed by Androgen deprivation therapy, (with cyclophosphamide/GVAX administered 4 weeks prior to prostatectomy, and Androgen deprivation therapy administered 2 weeks prior to prostatectomy).

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

29 participants

Primary outcome timeframe

2 years

Results posted on

2019-03-28

Participant Flow

Participant milestones

Participant milestones
Measure	Degarelix Degarelix will be administered as three 80 mg subcutaneous injections, for a total dose of 240 mg at 14 (±3) days prior to surgery. A telephone follow-up interview (or an in-person clinic visit) to evaluate for adverse events will occur 28 (±21) days after prostatectomy. Patients will then be followed by their urologists according to standard institutional practices, but will require prostate-specific antigen evaluations every 3 (±1) months during year 1 and every 6 (±2) months during years 2-3. degarelix acetate: Degarelix Acetate is a gonadotropin-releasing hormone (GnRH) receptor antagonist. It works by decreasing the amount of testosterone in the body,which the tumor needs to grow.	Cyclophosphamide, GVAX and Degarelix Cyclophosphamide will be given at a dose of 200 mg/m2 as a single intravenous infusion. 1 day later, prostate GVAX will be administered as five 0.8-mL intradermal injections of PC3 (2.5 × 108 cells) and five 0.5-mL intradermal injections of LNCaP (2.5 × 108 cells), for a total dose of 5 × 108 cells. On day 14, Degarelix will be administered as three 80 mg subcutaneous injections, for a total dose of 240 mg. degarelix acetate: Degarelix Acetate is a gonadotropin-releasing hormone (GnRH) receptor antagonist. It works by decreasing the amount of testosterone in the body,which the tumor needs to grow. Cyclophosphamide: Cyclophosphamide as a potent enhancer of immune responses to GVAX. cyclophosphamide is used as an immune suppressor in many autoimmune disorders. GVAX: GVAX is granulocytemacrophage-colony stimulating factor -secreting allogeneic cell-based vaccine as immunotherapy for prostate cancer
Overall Study STARTED	15	14
Overall Study COMPLETED	15	13
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Degarelix Degarelix will be administered as three 80 mg subcutaneous injections, for a total dose of 240 mg at 14 (±3) days prior to surgery. A telephone follow-up interview (or an in-person clinic visit) to evaluate for adverse events will occur 28 (±21) days after prostatectomy. Patients will then be followed by their urologists according to standard institutional practices, but will require prostate-specific antigen evaluations every 3 (±1) months during year 1 and every 6 (±2) months during years 2-3. degarelix acetate: Degarelix Acetate is a gonadotropin-releasing hormone (GnRH) receptor antagonist. It works by decreasing the amount of testosterone in the body,which the tumor needs to grow.	Cyclophosphamide, GVAX and Degarelix Cyclophosphamide will be given at a dose of 200 mg/m2 as a single intravenous infusion. 1 day later, prostate GVAX will be administered as five 0.8-mL intradermal injections of PC3 (2.5 × 108 cells) and five 0.5-mL intradermal injections of LNCaP (2.5 × 108 cells), for a total dose of 5 × 108 cells. On day 14, Degarelix will be administered as three 80 mg subcutaneous injections, for a total dose of 240 mg. degarelix acetate: Degarelix Acetate is a gonadotropin-releasing hormone (GnRH) receptor antagonist. It works by decreasing the amount of testosterone in the body,which the tumor needs to grow. Cyclophosphamide: Cyclophosphamide as a potent enhancer of immune responses to GVAX. cyclophosphamide is used as an immune suppressor in many autoimmune disorders. GVAX: GVAX is granulocytemacrophage-colony stimulating factor -secreting allogeneic cell-based vaccine as immunotherapy for prostate cancer
Overall Study Adverse Event	0	1

Baseline Characteristics

A Neoadjuvant Study of Androgen Ablation Combined With Cyclophosphamide and GVAX Vaccine for Localized Prostate Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Degarelix n=15 Participants Degarelix will be administered as three 80 mg subcutaneous injections, for a total dose of 240 mg at 14 (±3) days prior to surgery. A telephone follow-up interview (or an in-person clinic visit) to evaluate for adverse events will occur 28 (±21) days after prostatectomy. Patients will then be followed by their urologists according to standard institutional practices, but will require prostate-specific antigen evaluations every 3 (±1) months during year 1 and every 6 (±2) months during years 2-3. degarelix acetate: Degarelix Acetate is a gonadotropin-releasing hormone (GnRH) receptor antagonist. It works by decreasing the amount of testosterone in the body,which the tumor needs to grow.	Cyclophosphamide, GVAX and Degarelix n=14 Participants Cyclophosphamide will be given at a dose of 200 mg/m2 as a single intravenous infusion. 1 day later, prostate GVAX will be administered as five 0.8-mL intradermal injections of PC3 (2.5 × 108 cells) and five 0.5-mL intradermal injections of LNCaP (2.5 × 108 cells), for a total dose of 5 × 108 cells. On day 14, Degarelix will be administered as three 80 mg subcutaneous injections, for a total dose of 240 mg. degarelix acetate: Degarelix Acetate is a gonadotropin-releasing hormone (GnRH) receptor antagonist. It works by decreasing the amount of testosterone in the body,which the tumor needs to grow. Cyclophosphamide: Cyclophosphamide as a potent enhancer of immune responses to GVAX. cyclophosphamide is used as an immune suppressor in many autoimmune disorders. GVAX: GVAX is granulocytemacrophage-colony stimulating factor -secreting allogeneic cell-based vaccine as immunotherapy for prostate cancer	Total n=29 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	12 Participants n=93 Participants	12 Participants n=4 Participants	24 Participants n=27 Participants
Age, Categorical >=65 years	3 Participants n=93 Participants	2 Participants n=4 Participants	5 Participants n=27 Participants
Sex: Female, Male Female	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Sex: Female, Male Male	15 Participants n=93 Participants	14 Participants n=4 Participants	29 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants	2 Participants n=4 Participants	2 Participants n=27 Participants
Race (NIH/OMB) White	15 Participants n=93 Participants	12 Participants n=4 Participants	27 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Region of Enrollment United States	15 Participants n=93 Participants	14 Participants n=4 Participants	29 Participants n=27 Participants

PRIMARY outcome

Timeframe: 2 years

Outcome measures

Outcome measures
Measure	Degarelix n=15 Participants Degarelix will be administered as three 80 mg subcutaneous injections, for a total dose of 240 mg at 14 (±3) days prior to surgery. A telephone follow-up interview (or an in-person clinic visit) to evaluate for adverse events will occur 28 (±21) days after prostatectomy. Patients will then be followed by their urologists according to standard institutional practices, but will require prostate-specific antigen evaluations every 3 (±1) months during year 1 and every 6 (±2) months during years 2-3. degarelix acetate: Degarelix Acetate is a gonadotropin-releasing hormone (GnRH) receptor antagonist. It works by decreasing the amount of testosterone in the body,which the tumor needs to grow.	Cyclophosphamide, GVAX and Degarelix n=13 Participants Cyclophosphamide will be given at a dose of 200 mg/m2 as a single intravenous infusion. 1 day later, prostate GVAX will be administered as five 0.8-mL intradermal injections of PC3 (2.5 × 108 cells) and five 0.5-mL intradermal injections of LNCaP (2.5 × 108 cells), for a total dose of 5 × 108 cells. On day 14, Degarelix will be administered as three 80 mg subcutaneous injections, for a total dose of 240 mg. degarelix acetate: Degarelix Acetate is a gonadotropin-releasing hormone (GnRH) receptor antagonist. It works by decreasing the amount of testosterone in the body,which the tumor needs to grow. Cyclophosphamide: Cyclophosphamide as a potent enhancer of immune responses to GVAX. cyclophosphamide is used as an immune suppressor in many autoimmune disorders. GVAX: GVAX is granulocytemacrophage-colony stimulating factor -secreting allogeneic cell-based vaccine as immunotherapy for prostate cancer
Intraprostatic CD8+ T Cell Infiltration	204.81 log10 (cells/mm^2) Interval 120.67 to 288.95	263.33 log10 (cells/mm^2) Interval 129.4 to 397.25

SECONDARY outcome

Timeframe: 2 years

Population: Data was not collected for this outcome measure

Number of participants with CD4+ T cell and Treg infiltration into the prostate.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2 years

Population: Data was not collected for this outcome measure

Tissue androgen concentrations (testosterone, dihydrotestosterone), and androgen receptor (AR) protein expression in prostate specimens

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2 years

Population: Data was not collected for this outcome measure

Amount of apoptosis (activated caspase 3) and proliferation (Ki-67) in prostate tumor specimens

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2 years

Number of participants with pathological complete response (pCR)

Outcome measures

Outcome measures
Measure	Degarelix n=15 Participants Degarelix will be administered as three 80 mg subcutaneous injections, for a total dose of 240 mg at 14 (±3) days prior to surgery. A telephone follow-up interview (or an in-person clinic visit) to evaluate for adverse events will occur 28 (±21) days after prostatectomy. Patients will then be followed by their urologists according to standard institutional practices, but will require prostate-specific antigen evaluations every 3 (±1) months during year 1 and every 6 (±2) months during years 2-3. degarelix acetate: Degarelix Acetate is a gonadotropin-releasing hormone (GnRH) receptor antagonist. It works by decreasing the amount of testosterone in the body,which the tumor needs to grow.	Cyclophosphamide, GVAX and Degarelix n=13 Participants Cyclophosphamide will be given at a dose of 200 mg/m2 as a single intravenous infusion. 1 day later, prostate GVAX will be administered as five 0.8-mL intradermal injections of PC3 (2.5 × 108 cells) and five 0.5-mL intradermal injections of LNCaP (2.5 × 108 cells), for a total dose of 5 × 108 cells. On day 14, Degarelix will be administered as three 80 mg subcutaneous injections, for a total dose of 240 mg. degarelix acetate: Degarelix Acetate is a gonadotropin-releasing hormone (GnRH) receptor antagonist. It works by decreasing the amount of testosterone in the body,which the tumor needs to grow. Cyclophosphamide: Cyclophosphamide as a potent enhancer of immune responses to GVAX. cyclophosphamide is used as an immune suppressor in many autoimmune disorders. GVAX: GVAX is granulocytemacrophage-colony stimulating factor -secreting allogeneic cell-based vaccine as immunotherapy for prostate cancer
Pathological Complete Responses	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 2 years

Population: Data was not collected for this outcome measure

Number of participants with generation of novel antibodies to prostate-associated antigens in the serum of patients, after the initiation of protocol therapy

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2 years

Number of participants with Prostate-specific antigen response

Outcome measures

Outcome measures
Measure	Degarelix n=15 Participants Degarelix will be administered as three 80 mg subcutaneous injections, for a total dose of 240 mg at 14 (±3) days prior to surgery. A telephone follow-up interview (or an in-person clinic visit) to evaluate for adverse events will occur 28 (±21) days after prostatectomy. Patients will then be followed by their urologists according to standard institutional practices, but will require prostate-specific antigen evaluations every 3 (±1) months during year 1 and every 6 (±2) months during years 2-3. degarelix acetate: Degarelix Acetate is a gonadotropin-releasing hormone (GnRH) receptor antagonist. It works by decreasing the amount of testosterone in the body,which the tumor needs to grow.	Cyclophosphamide, GVAX and Degarelix n=13 Participants Cyclophosphamide will be given at a dose of 200 mg/m2 as a single intravenous infusion. 1 day later, prostate GVAX will be administered as five 0.8-mL intradermal injections of PC3 (2.5 × 108 cells) and five 0.5-mL intradermal injections of LNCaP (2.5 × 108 cells), for a total dose of 5 × 108 cells. On day 14, Degarelix will be administered as three 80 mg subcutaneous injections, for a total dose of 240 mg. degarelix acetate: Degarelix Acetate is a gonadotropin-releasing hormone (GnRH) receptor antagonist. It works by decreasing the amount of testosterone in the body,which the tumor needs to grow. Cyclophosphamide: Cyclophosphamide as a potent enhancer of immune responses to GVAX. cyclophosphamide is used as an immune suppressor in many autoimmune disorders. GVAX: GVAX is granulocytemacrophage-colony stimulating factor -secreting allogeneic cell-based vaccine as immunotherapy for prostate cancer
Prostate-specific Antigen Response Rate	13 Participants	11 Participants

SECONDARY outcome

Timeframe: 2 years

Percentage of participants in each arm who were free of prostate specific antigen recurrence (i.e. prostate specific antigen remained undetectable after prostatectomy) at 24 months after undergoing surgery.

Outcome measures

Outcome measures
Measure	Degarelix n=15 Participants Degarelix will be administered as three 80 mg subcutaneous injections, for a total dose of 240 mg at 14 (±3) days prior to surgery. A telephone follow-up interview (or an in-person clinic visit) to evaluate for adverse events will occur 28 (±21) days after prostatectomy. Patients will then be followed by their urologists according to standard institutional practices, but will require prostate-specific antigen evaluations every 3 (±1) months during year 1 and every 6 (±2) months during years 2-3. degarelix acetate: Degarelix Acetate is a gonadotropin-releasing hormone (GnRH) receptor antagonist. It works by decreasing the amount of testosterone in the body,which the tumor needs to grow.	Cyclophosphamide, GVAX and Degarelix n=13 Participants Cyclophosphamide will be given at a dose of 200 mg/m2 as a single intravenous infusion. 1 day later, prostate GVAX will be administered as five 0.8-mL intradermal injections of PC3 (2.5 × 108 cells) and five 0.5-mL intradermal injections of LNCaP (2.5 × 108 cells), for a total dose of 5 × 108 cells. On day 14, Degarelix will be administered as three 80 mg subcutaneous injections, for a total dose of 240 mg. degarelix acetate: Degarelix Acetate is a gonadotropin-releasing hormone (GnRH) receptor antagonist. It works by decreasing the amount of testosterone in the body,which the tumor needs to grow. Cyclophosphamide: Cyclophosphamide as a potent enhancer of immune responses to GVAX. cyclophosphamide is used as an immune suppressor in many autoimmune disorders. GVAX: GVAX is granulocytemacrophage-colony stimulating factor -secreting allogeneic cell-based vaccine as immunotherapy for prostate cancer
Percentage of Participants Without Prostate Specific Antigen Recurrence at 24 Months After Surgery	38 percentage of participants Interval 19.0 to 74.0	66 percentage of participants Interval 43.0 to 100.0

Adverse Events

Degarelix

Serious events: 1 serious events

Other events: 15 other events

Deaths: 0 deaths

Cyclophosphamide, GVAX and Degarelix

Serious events: 2 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Degarelix n=15 participants at risk Degarelix will be administered as three 80 mg subcutaneous injections, for a total dose of 240 mg at 14 (±3) days prior to surgery. A telephone follow-up interview (or an in-person clinic visit) to evaluate for adverse events will occur 28 (±21) days after prostatectomy. Patients will then be followed by their urologists according to standard institutional practices, but will require prostate-specific antigen evaluations every 3 (±1) months during year 1 and every 6 (±2) months during years 2-3. degarelix acetate: Degarelix Acetate is a gonadotropin-releasing hormone (GnRH) receptor antagonist. It works by decreasing the amount of testosterone in the body,which the tumor needs to grow.	Cyclophosphamide, GVAX and Degarelix n=14 participants at risk Cyclophosphamide will be given at a dose of 200 mg/m2 as a single intravenous infusion. 1 day later, prostate GVAX will be administered as five 0.8-mL intradermal injections of PC3 (2.5 × 108 cells) and five 0.5-mL intradermal injections of LNCaP (2.5 × 108 cells), for a total dose of 5 × 108 cells. On day 14, Degarelix will be administered as three 80 mg subcutaneous injections, for a total dose of 240 mg. degarelix acetate: Degarelix Acetate is a gonadotropin-releasing hormone (GnRH) receptor antagonist. It works by decreasing the amount of testosterone in the body,which the tumor needs to grow. Cyclophosphamide: Cyclophosphamide as a potent enhancer of immune responses to GVAX. cyclophosphamide is used as an immune suppressor in many autoimmune disorders. GVAX: GVAX is GM-CSF-secreting allogeneic cell-based vaccine as immunotherapy for prostate cancer
Vascular disorders Hematoma	6.7% 1/15 • Number of events 1 • Participants were assessed for adverse events after receiving study drug and before prostatectomy as well as doing each follow up visit after prostatectomy up to 3 years. An adverse event (AE) is defined as any untoward medical occurrence (symptom, sign, illness or experience) that develops or worsens in a research patient during a clinical study or within 30 days post-treatment, regardless of causality.	7.1% 1/14 • Number of events 1 • Participants were assessed for adverse events after receiving study drug and before prostatectomy as well as doing each follow up visit after prostatectomy up to 3 years. An adverse event (AE) is defined as any untoward medical occurrence (symptom, sign, illness or experience) that develops or worsens in a research patient during a clinical study or within 30 days post-treatment, regardless of causality.
Nervous system disorders Stroke	0.00% 0/15 • Participants were assessed for adverse events after receiving study drug and before prostatectomy as well as doing each follow up visit after prostatectomy up to 3 years. An adverse event (AE) is defined as any untoward medical occurrence (symptom, sign, illness or experience) that develops or worsens in a research patient during a clinical study or within 30 days post-treatment, regardless of causality.	7.1% 1/14 • Number of events 1 • Participants were assessed for adverse events after receiving study drug and before prostatectomy as well as doing each follow up visit after prostatectomy up to 3 years. An adverse event (AE) is defined as any untoward medical occurrence (symptom, sign, illness or experience) that develops or worsens in a research patient during a clinical study or within 30 days post-treatment, regardless of causality.
Vascular disorders Thromboembolic event	6.7% 1/15 • Number of events 1 • Participants were assessed for adverse events after receiving study drug and before prostatectomy as well as doing each follow up visit after prostatectomy up to 3 years. An adverse event (AE) is defined as any untoward medical occurrence (symptom, sign, illness or experience) that develops or worsens in a research patient during a clinical study or within 30 days post-treatment, regardless of causality.	0.00% 0/14 • Participants were assessed for adverse events after receiving study drug and before prostatectomy as well as doing each follow up visit after prostatectomy up to 3 years. An adverse event (AE) is defined as any untoward medical occurrence (symptom, sign, illness or experience) that develops or worsens in a research patient during a clinical study or within 30 days post-treatment, regardless of causality.

Other adverse events

Additional Information

Emmanuel S. Antonarakis, M.D., principal investigator

Johns Hopkins University

Phone: 443-287-0553

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place