Adenocarcinoma of the Prostate
Conditions
Keywords
ISUP Grade Group 1 or 2, Number biopsies 1 or >1 (≤12 months of Screening)
Brief summary
The ProVent study is a randomized, open-label study designed to assess the efficacy of sipuleucel-T in reducing the progression of lower risk non-metastatic prostate cancer compared to participants followed on active surveillance as standard of care.
Detailed description
The ProVent Study is designed to look at participants who receive sipuleucel-T compared to control participants followed on active surveillance (AS). The study will enroll participants being followed by AS and initially diagnosed within 12 months prior to Screening with either International Society of Urological Pathology (ISUP) Grade Group 1 or 2 adenocarcinoma of the prostate. The Screening Phase will begin at the completion of the informed consent process and continues until randomization. After Screening assessments are completed, eligible participants will be randomized 2:1 to the sipuleucel-T arm or the control arm. Participants randomized to sipuleucel-T arm will receive product as described in the sipuleucel-T approved label. Participants will undergo their first leukapheresis within 60 days of randomization. Participants randomized to the control arm will be followed on AS. The Active Phase will begin at randomization and continues through completion of the end of Active Phase study visit (within 30 days of Biopsy 2). Once a Participant from either the sipuleucel-T or control arms completes the end of Active Phase visit, they will enter the Follow-up Phase and complete Follow-up Phase visits every 6 months starting from their last Active Phase visit. The Follow-up Phase visits end when the last Participant enrolled completes Biopsy 2 and end of Active Phase visit or until the study is terminated by the sponsor.
Interventions
BIOLOGICALsipuleucel-T
Sipuleucel-T is an autologous cell product consisting of antigen presenting cells (APCs) loaded with recombinant fusion protein composed PAP linked to GM-CSF (PA2024), a recombinant fusion protein composed of prostatic acid phosphatase (PAP), linked to granulocyte-macrophage colony-stimulating factor (GM-CSF).
Sponsors
PRA Health Sciences
Dendreon
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participants will be randomized 2:1 to the sipuleucel-T arm or the control arm.Participants randomized to sipuleucel-T arm will receive 3 infusions of sipuleucel-T at approximately 2-week intervals. Participants randomized to the control arm will be followed on AS as standard of care described in the schedule of events.
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 1\. Age is ≥ 18 years * 2\. Written informed consent provided prior to the initiation of study procedures * 3\. Histologically proven adenocarcinoma of the prostate initially diagnosed ≤12 months of Screening. All biopsy slides with participant information redacted must be submitted for blinded independent central review (BICR). * 4\. Prostate cancer diagnosis determined by BICR as one of the following: 4a. ISUP Grade Group 1 with 3 or more cores positive from a systematic (≥10 cores) biopsy 4b. ISUP Grade Group 1 with ≥ 1 core positive with ≥50% cancer involvement from a systematic (≥10 cores) biopsy 4c. ISUP Grade Group 1 from 3 or more positive cores from any combination of cores from a systematic (≥10 cores) biopsy and MRI targeted biopsy (note: multiple cores from each MRI targeted lesion will count as 1 core) 4d. ISUP Grade Group 1 from a negative systematic (≥10 cores) biopsy and an MRI targeted core positive with ≥50% cancer involvement 4e. ISUP Grade Group 2 from a systematic (≥10 cores) biopsy with \<50% of the total number of any cores positive for cancer 4f. ISUP Grade Group 2 from a negative systematic (≥10 cores) biopsy and MRI targeted core(s) positive for Gleason 3+4 (see note below) 4g. ISUP Grade Group 2 from any combination of cores from a systematic (≥10 cores) biopsy and MRI targeted biopsy (see note below) Note for 4f and 4g: the total number of positive cores must be \<50% of total cores from both the systematic biopsy and MRI targeted lesions; each MRI targeted lesion, irrespective of multiple positive cores, will each count as 1 core for the total number of positive cores, e.g., 4 targeted lesions with 2 positive cores each will only add 4 to the total core count. * 5\. Participant consents to standard of care for biopsy frequency of 2 on-study prostate biopsies and to provide biopsy tissue for study endpoint analysis. * 6\. Estimated life expectancy ≥ 10 years * 7\. Candidate for primary curative therapy (e.g., surgery or radiation) if prostate cancer progression occurs * 8\. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * 9\. Adequate baseline hematologic, renal, and liver function tests as evidenced by laboratory test results within the following ranges ≤30 days prior to randomization White blood cell (WBC) count ≥ 3.0 x 10\^6 cells/mL Absolute neutrophil count (ANC) ≥ 1.5 x 10\^6 cells/mL Platelet count ≥ 1.0 x10\^5 cells/uL Hemoglobin (Hgb) ≥ 10.0 g/dL Creatinine ≤ 1.5 mg/dL Total bilirubin ≤ 1.5 x upper limit of normal (ULN) Alanine aminotransferase (ALT) ≤ 2.0 x ULN Aspartate aminotransferase (AST) ≤ 2.0 x ULN
Exclusion criteria
* 1\. Former therapy for prostate cancer (local or systemic) * 2\. Any previous prostatic surgical procedure that significantly changes the anatomy of prostate (at the discretion of sponsor's Medical Monitor) * 3\. Any investigational product received for prostate cancer * 4\. Prostate biopsy specimen reveals neuroendocrine or small cell features * 5\. Primary Gleason score is ≥ 4 or any Gleason pattern 5 * 6\. Any evidence of locally advanced, regional or metastatic disease, including regional and distant lymph node enlargement (Nodes ≥1.5 cm in the short axis are considered pathologic and measurable) * 7\. A history of a cerebrovascular event (CVE) or transient ischemic attack (TIA) * 8\. Participant has used a 5-alpha-reductase inhibitor (e.g., finasteride or dutasteride) continuously for ≥ 6 months and within 6 months prior to study Screening * 9\. Participant has a history of any other stage I-IV malignancy, except for basal or squamous cell skin cancer. The Participant must be disease free and off any malignancy-related treatment for at least 5 years. * 10\. Participant has prior use within 30 days of study Screening of any herbal, dietary, or alternative anti-cancer treatment or product, such as PC-SPES (or PC-x product), saw palmetto, ketoconazole, an estrogen-containing nutraceutical, or high dose calcitriol (\>0.5 μg/day). The Investigator will consider herbal therapies on a case-by-case basis to determine whether they fall into the category of prohibited medications based on their potential for hormonal or anti-cancer or anti-cancer properties. * 11\. Need for systemic chronic immunosuppressive therapy (e.g., anti-tumor necrosis factor alpha monoclonal antibodies, glucocorticoids) * 12\. Uncontrolled, concurrent illness including, but not limited to the following: ongoing or active infection (bacterial, viral, or fungal), symptomatic congestive heart failure (New York Classification III-IV) or unstable angina pectoris within the last 6 months, or psychiatric illness that would limit compliance with study requirements as well as any condition that would preclude a participant from undergoing leukapheresis (e.g., within the previous 6 months: myocardial infarction, interventional cardiology procedure such as angioplasty or stent placement, pulmonary embolism or deep vein thrombosis). * 13\. Hypogonadal (T \<175 ng/dL) or on continuous testosterone replacement therapy * 14\. Positive serology for HIV-1, HIV-2 or human T-lymphotropic virus (HTLV)-1, HTLV-2 * 15\. Active hepatitis B or C * 16\. Any medical intervention, any other condition, or any other circumstance which, in the opinion of the investigator or the sponsor's Medical Monitor, could compromise adherence with study requirements or otherwise compromise the study's objectives.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of Sipuleucel-T Measured as the Percentage of Subjects Without Histological Reclassification (Gleason Group Upgrade). | Once all participants have completed at least 3 years following randomization | Percentage of participants without histological reclassification (Gleason group upgrade) within 36 months of randomization as determined by Blinded Independent Central Review (BICR) o Upgrade is defined as participants at randomization with either International Society of Urological Pathology (ISUP) Grade Group 1 (Gleason 3+3) upgraded to Grade Group 2 (Gleason 3+4) or higher or participants at randomization with Grade Group 2 upgraded to Grade Group 3 (Gleason 4+3) or higher. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Group: Sipuleucel-T Sipuleucel-T is an autologous cellular immunotherapy available as a suspension for intravenous infusion. Subjects randomized to sipuleucel-T arm will receive 3 infusions of sipuleucel-T at approximately 2-week intervals.
sipuleucel-T: Sipuleucel-T is an autologous cell product consisting of antigen presenting cells (APCs) loaded with PA2024, a recombinant fusion protein composed of prostatic acid phosphatase (PAP), linked to granulocyte-macrophage colony-stimulating factor (GM-CSF). | 356 |
| Control Arm: Active Surveillance Subjects randomized to the control arm will be followed on Active Surveillance described in the schedule of events. | 176 |
| Total | 532 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Death | 10 | 5 |
| Overall Study | Lost to Follow-up | 23 | 19 |
| Overall Study | No data available | 1 | 0 |
| Overall Study | Noncompliance | 1 | 0 |
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Progressive Disease | 1 | 1 |
| Overall Study | Protocol Violation | 3 | 0 |
| Overall Study | Screen fail post-randomization | 1 | 0 |
| Overall Study | Withdrawal by Subject | 52 | 32 |
Baseline characteristics
| Characteristic | Treatment Group: Sipuleucel-T | Control Arm: Active Surveillance | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 173 Participants | 84 Participants | 257 Participants |
| Age, Categorical Between 18 and 65 years | 183 Participants | 92 Participants | 275 Participants |
| Age, Continuous | 64.1 years STANDARD_DEVIATION 7.27 | 63.9 years STANDARD_DEVIATION 7.72 | 64.0 years STANDARD_DEVIATION 7.41 |
| Body Mass Index | 29.1 kg/m^2 STANDARD_DEVIATION 5 | 28.8 kg/m^2 STANDARD_DEVIATION 5.4 | 29.0 kg/m^2 STANDARD_DEVIATION 5.1 |
| Height | 177.4 centimeters STANDARD_DEVIATION 6.7 | 178.1 centimeters STANDARD_DEVIATION 7.7 | 177.6 centimeters STANDARD_DEVIATION 7.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 4 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 38 Participants | 21 Participants | 59 Participants |
| Race (NIH/OMB) More than one race | NA Participants | NA Participants | NA Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) White | 309 Participants | 152 Participants | 461 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 356 Participants | 176 Participants | 532 Participants |
| Weight | 91.6 kilograms STANDARD_DEVIATION 16.7 | 91.7 kilograms STANDARD_DEVIATION 20 | 91.7 kilograms STANDARD_DEVIATION 17.9 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 10 / 356 | 5 / 176 |
| other Total, other adverse events | 321 / 345 | 133 / 176 |
| serious Total, serious adverse events | 74 / 345 | 22 / 176 |
Outcome results
Primary
Efficacy of Sipuleucel-T Measured as the Percentage of Subjects Without Histological Reclassification (Gleason Group Upgrade).
Percentage of participants without histological reclassification (Gleason group upgrade) within 36 months of randomization as determined by Blinded Independent Central Review (BICR) o Upgrade is defined as participants at randomization with either International Society of Urological Pathology (ISUP) Grade Group 1 (Gleason 3+3) upgraded to Grade Group 2 (Gleason 3+4) or higher or participants at randomization with Grade Group 2 upgraded to Grade Group 3 (Gleason 4+3) or higher.
Time frame: Once all participants have completed at least 3 years following randomization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Group: Sipuleucel-T | Efficacy of Sipuleucel-T Measured as the Percentage of Subjects Without Histological Reclassification (Gleason Group Upgrade). | 108 Participants |
| Control Arm: Active Surveillance | Efficacy of Sipuleucel-T Measured as the Percentage of Subjects Without Histological Reclassification (Gleason Group Upgrade). | 48 Participants |
p-value: 0.458695% CI: [0.78, 1.74]Cochran-Mantel-Haenszel