Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Provenge

Steven Finkelstein, MD

Radiation in combination with Provenge based immunotherapy may improve outcomes seen on imaging as well as immunologic monitoring. This study will assess the effect of radiation therapy to augment anti-tumor responses from immune therapy with Provenge.

It is common knowledge that the host can make anti-tumor immune responses, although often these are ineffective in causing tumor regression. Boosting these responses with immunotherapy is therefore an attractive, relatively benign adjunctive cancer treatment. Little is known in regards to how standard anti-cancer therapies like radiation therapy might interact with immunotherapy in a clinical setting. We are interested in knowing if the tumor cell death occasioned by radiation therapy might augment anti-tumor responses from the immune therapy, Provenge.

The tentative assumption is that cell death following radiation therapy will stimulate anti-tumor immunity, which could provide a more permanent solution to curing cancer and discouraging tumors from spreading throughout the body. In order to find out if this assumption is correct, for patients undergoing radiation 28 days prior to Provenge, highly developed, laboratory analyses for tumor-specific immunity and imaging will be performed.

A Multicenter Trial Enrolling Men With Advanced Prostate Cancer Who Are to Receive Combination Radiation and Sipuleucel-T

The percentage of subjects who exhibit a two-fold increase in peripheral immune response at any post-treatment time point (6, 10, 14, 26, 39 and 52 weeks after the first infusion of sipuleucel-T) utilizing IFNγ ELISPOT response to PA2024.

Dendreon

GenesisCare USA

Symptoms and General Pathology

Immune System Diseases

Recurrence

Hypersensitivity

All Drugs and Chemicals

Antineoplastic Agents

Androgens

Molgramostim

Sargramostim

Vaccines

Immunomodulating Agents

Subjects received infusion of Sipuleucel-T, at 2-week intervals, for a total of 3 infusions.

Subjects received infusion of control (autologous cellular product consisting of antigen presenting cells (APCs) prepared in the absence of PA2024 antigen) at 2-week intervals, for a total of 3 infusions.

Autologous cellular product consisting of antigen presenting cells (APCs) prepared in the absence of PA2024 antigen.

Control

Sipuleucel-T is an autologous cellular product consisting of antigen presenting cells (APCs) activated with PA2024, a recombinant fusion protein composed of prostatic acid phosphatase (PAP), linked to granulocyte-macrophage colony-stimulating factor (GM-CSF).

Sipuleucel-T

Robert Israel, MD

The PROTECT-PROvenge Treatment and Early Cancer Treatment trial was a Phase III trial for patients with hormone sensitive prostate cancer. The study was conducted at over 15 participating centers throughout the US. The purpose of the study was to determine if sipuleucel-T was effective for treatment of early stage, non-metastatic prostate cancer. The study compared the active vaccine to control to determine whether the product delayed the time until cancer progression.

This was a prospective, double blind, controlled, randomized trial of immunotherapy with prostatic acid phosphatase (PAP)-loaded autologous antigen presenting cells (APCs), in subjects with non metastatic prostate cancer. Subjects that qualified for this study were men who had previously undergone a prostatectomy and whose only sign of disease recurrence was a rise in serum prostate specific antigen (PSA).

The primary objectives were to compare the time to biochemical failure (BF, PSA greater than or equal to 3 ng/mL) between sipuleucel-T (treatment group) and control, and to study the safety of sipuleucel-T.

Following short-term open-label treatment with a luteinizing hormone-releasing hormone-analogue (LHRH-a), Subjects completed a checklist designed to compare androgen suppression-related side effects during periods with and without androgen suppression.

Subjects who achieved a PSA of \< 1 ng/ml were randomized to blinded treatment assignments of either sipuleucel-T or control in a 2:1 ratio. Following randomization, subjects underwent 3 leukapheresis procedures on alternate weeks (Weeks 0, 2, and 4). Approximately three days following each leukapheresis procedure, subjects received an infusion of either sipuleucel-T or control.

At the time BF was confirmed, subjects were eligible for a booster infusion. The booster process consisted of 1 leukapheresis procedure followed by 1 infusion of sipuleucel-T. The booster process, in effect under protocol amendment 5, differed from the previous booster process that consisted of 1 infusion of the same treatment assigned at randomization (sipuleucel-T or control).

Subjects continued to be observed until DF was confirmed by bone scan or computed tomography (CT) scan, or other imaging modalities as clinically indicated. After confirmed DF, subjects were followed by telephone every 6 months for safety and survival, treatment-related AEs, any CVEs, or new therapies for prostate cancer.

PROvenge Treatment and Early Cancer Treatment

Autologous PAP-loaded Dendritic Cell Vaccine (Sipuleucel-T, APC8015, Provenge®) in Patients With Non-metastatic Prostate Cancer Who Experience PSA Elevation Following Radical Prostatectomy: a Randomized, Controlled, Double-blind Trial

Time to Biochemical Failure (TTBF) was the pre-specified primary endpoint of this trial. The biochemical failure threshold was based on evidence that prostate specific antigen (PSA) had become ≥ 3 ng/mL

time to biochemical Failure (TTBF) was the pre-scpecified primary endpoint of this trial. The biochemical failure threshold was based on evidence that prostate specific antigen (PSA) had become ≥ 3 ng/mL.

Provenge

Provenge: Biologic: autologous cellular product consisting of antigen presenting cells (APCs) activated with PA2024, a recombinant fusion protein composed of PAP, linked to GM-CSF

Control

Control: Autologous cellular product consisting of antigen presenting cells (APCs) prepared in the absence of PA2024 antigen

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

ECOG 0=Fully Active; No restrictions.

ECOG 1= Restricted Strenuous Activity

ECOG Missing

ECOG Performance Status is a method used to assess the functional status of a patient. The scale ranges from 0-5. 0=Fully active, able to carry on all pre-disease performance without restriction; 1=Restricted in physically strenuous activity but ambulatory and able to carry out light or sedentary work; 2=Ambulatory, capable of all self-care but unable to carry out work activities. Up and about \>50% of waking hour; 3=Capable of limited self-care, confined to bed or chair \>50% of waking hours; 4=Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair; 5=Dead

Eastern Cooperative Oncology Group (ECOG) Performance Status

Weight

Gleason Score ≤ 6

Gleason Score =7

Gleason Score ≥ 8

Gleason score= prostate cancer grading system based on how tissue looks under a microscope. Scores range 2-10 and indicates how likely it is that a tumor will spread. A low score means the cancer tissue is similar to normal tissue and the tumor is less likely to spread. Gleason Score ≤ 6=the tumor is well differentiated, less aggressive and likely to grow more slowly;7=the tumor is moderately differentiated, moderately aggressive, and likely to grow but may not spread quickly;≥8=the tumor is poorly differentiated or undifferentiated, highly aggressive, and likely to grow faster and spread.

Gleason Score

Time from diagnosis to randomization

Shabnam Vaziri

25th Cumulative Incidence Percentile

50th Cumulative Incidence Percentile

75th Cumulative Incidence Percentile

Number of subjects that met biochemical failure criteria.

Time to Biochemical Failure Cumulative Incidence Percentile

Number of Subjects That Met Biochemical Failure Status

Treatment Phase 1

Surveillance Phase

Long-term Follow-up

Castration Resistant Metastatic Prostate Cancer with no history of prior systemic chemotherapy

Matthew Galsky, MD

The purpose of this protocol is perform comprehensive immune monitoring studies in patients with castration-resistant prostate cancer receiving Sipuleucel-T in an effort to better understand the mechanism of action of this treatment.

The primary objectives of this study are to:

1. Establish the phenotype and frequency of circulating immune cell compartments in patients undergoing treatment with Sipuleucel-T.
2. Determine the induction and the quality of prostate antigen-specific T cell immunity in patients undergoing treatment with Sipuleucel-T.
3. Correlate whole-blood RNA transcript-based signatures with clinical outcomes in patients treated with Sipuleucel-T.
4. Evaluate the cytokine and chemokine milieu in the peripheral blood pre- and post-treatment with Sipuleucel-T.

Immune Monitoring on Sipuleucel-T

A Systems Biology Approach to Immune Monitoring in Patients With Castration-resistant Prostate Cancer Receiving SiPuleucel-T

Establish the phenotype and frequency of circulating immune cell compartments in patients undergoing treatment with Sipuleucel-T looking at the change in regulatory T cells at 1 year post treatment compared to at baseline

Establish the phenotype and frequency of circulating immune cell compartments in patients undergoing treatment with Sipuleucel-T looking at the change in antigen presenting cells: DCs and B cells at 1 year post treatment compared to at baseline

whole-blood RNA transcript-based signatures correlate with overall survival

Icahn School of Medicine at Mount Sinai

Ipilimumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Arm 1 (Immediate Treatment) Ipilimumab Q3wks x 4 started 1 day following the final dose of SipT.

Arm 2 (Delayed Treatment) Ipilimumab Q3wks x 4 started 3 weeks following the final dose of SipT.

All patients will receive standard of care SipT treatment every two weeks for a total of 3 treatments. The three treatments usually take about 30 days to complete.

SipT treatment is given in three 1 hour infusions. Each SipT treatment is generated from a standard blood cell-collection procedure (called leukapheresis) performed 2-3 days prior to the infusion.

SipT Treatment

Ipilimumab will be given by IV over 90 minutes every 3 weeks. Patients will be monitored during the infusion and up to 1 hour post-infusion.

Lawrence Fong, MD

Padmanee Sharma, MD

The purpose of this study is to find out what effects taking ipilimumab, as an immediate or delayed treatment, following completion of sipuleucel-T (SipT) treatment, has on patients and their prostate cancer.

This is an open-label randomized multicenter Phase 2 clinical trial combining SipT with ipilimumab in patients with chemotherapy-naïve metastatic castration resistant prostate cancer (CRPC).

All patients will be treated with standard SipT (Q2wks x 3). Patients will be randomized to one of two arms:

Arm 1 (Immediate Treatment): Ipilimumab Q3wks x 4 started 1 day following the final dose of SipT (Day 0).

Arm 2 (Delayed Treatment): Ipilimumab Q3wks x 4 started 3 weeks following the final dose of SipT (Day 0).

Following this ipilimumab treatment, patients will then be followed monthly for 3 months and then quarterly until disease progression. The definition of unacceptable toxicity is grade 3 or higher treatment-related toxicities (NCI CTCAE v4) excluding immune-related adverse events (irAEs). The study will assess for the immunogenicity and clinical activity of sequential sipuleucel-T treatment followed by ipilimumab. Patients who experience an initial clinical response to ipilimumab followed by subsequent disease progression will be offered reinduction treatment with ipilimumab.

Sipuleucel-T With Immediate vs. Delayed Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA-4) Blockade for Prostate Cancer

A Randomized Phase 2 Trial of Immediate vs. Delayed Anti-CTLA4 Blockade Following Sipuleucel-T Treatment for Prostate Cancer Immunotherapy

Immune response will be tested using the single sample binomial exact test when induction therapy is completed. The Immunoglobulin M (IgM) and Immunoglobulin G (IgG) antibody responses to PAP and/or PA2024 will be assessed by ELISA assay at baseline and week 20 after start of sipT treatment (day 113 of study treatment). A positive response is defined as a titer \> 1:400. The positive immune percentage for both IgG and IgM antibodies to PAP and to PA2024 will be used to summarize the results for each study arm.

Immune Response Adverse Events (IRAEs) will be reported for each study arm by tabulating the frequency of the maximum grade occurring for each patient for each type of iRAE using NCI Common Terminology Criteria for Adverse Events (CTCAE) v. 4.0. IRAEs will be reported as a proportion of the participants in the treatment arm with the associated highest grade IRAE occurrences during protocol therapy.

Descriptive statistics will be calculated to characterize the proportion of patients achieving a PSA decline of at least \>30% after 1 cycle of treatment and presented along with the 95% confidence intervals for each study arm.

Descriptive statistics will be calculated to characterize the proportion of patients achieving a PSA decline of at least \>50% and presented along with the 95% confidence intervals for each study arm.

Proportion of patients achieving an objective response as defined by Immune-related Response Evaluation Criteria In Solid Tumors (irRECIST) as complete response (irCR), partial response (irPR) will be reported along with 95% confidence intervals

Proportion of patients achieving an objective response as defined by irRECIST as irCR +irPR and stratified by history of prior RP will be reported along with 95% confidence intervals.

Proportion of patients achieving an objective response as defined by irRECIST as irCR + irPR stratified by prior RT will be reported along with 95% confidence intervals

For each treatment arm, for patients with objective disease, using immune-related response criteria (irRC) criteria, the proportion of patients achieving a complete or partial response will be determined and reported with 95% confidence intervals

Time to PSA progression is defined as the start of protocol therapy to progression status at the end of 4 cycles of treatment as determined by the irRECIST.

M.D. Anderson Cancer Center

Bristol-Myers Squibb

University of California, San Francisco

Arm 1 (Immediate Treatment) Ipilimumab Q3wks x 4 started 1 day following the final dose of SipT.

SipT Treatment: All patients will receive standard of care SipT treatment every two weeks for a total of 3 treatments. The three treatments usually take about 30 days to complete.

SipT treatment is given in three 1 hour infusions. Each SipT treatment is generated from a standard blood cell-collection procedure (called leukapheresis) performed 2-3 days prior to the infusion.

Ipilimumab: Ipilimumab will be given by IV over 90 minutes every 3 weeks. Patients will be monitored during the infusion and up to 1 hour post-infusion.

Immediate IpilimumabTreatment

Arm 2 (Delayed Treatment) Ipilimumab Q3wks x 4 started 3 weeks following the final dose of SipT.

SipT Treatment: All patients will receive standard of care SipT treatment every two weeks for a total of 3 treatments. The three treatments usually take about 30 days to complete.

SipT treatment is given in three 1 hour infusions. Each SipT treatment is generated from a standard blood cell-collection procedure (called leukapheresis) performed 2-3 days prior to the infusion.

Ipilimumab: Ipilimumab will be given by IV over 90 minutes every 3 weeks. Patients will be monitored during the infusion and up to 1 hour post-infusion.

Delayed IpilimumabTreatment

50-59 years old

60-69 years old

70-79 years old

Age, Customized

Ethnicity (NIH/OMB)

Dr. Lawrence Fong, MD

Only a small portion of the collected samples contained enough aliquots or tissue available for this particular analysis

Percentage of Participants With an Immune Response to Prostatic Acid Phosphatase (PAP) and/or PA2024

Grade 2 Adrenal Insufficiency

Grade 3 Adrenal insufficiency

Grade 3 Diarrhea

Grade 4 Diarrhea

Grade 2 Hyperthyroidism

Grade 1 Hypothyroidism

Grade 2 Hypothyroidism

Grade 3 Lipase increased

Grade 2 Rash

Grade 3 Rash

Proportion of Participants With Highest Grade, Treatment-related, Immune Response Adverse Events (IRAEs)

Proportion of Patients Achieving a Prostate-specific Antigen (PSA) Decline of at Least 30% Below Baseline

Proportion of Patients Achieving a PSA Decline of at Least 50% Below Baseline

Proportion of Patients Achieving an Objective Response

Proportion of Patients Achieving an Objective Response Stratified by Prior Radical Prostatectomy (RP)

Proportion of Patients Achieving an Objective Response Stratified by Radiation Therapy (RT)

Radiographic Clinical Response Rate

Median Time to PSA Progression

Arm 1 (Immediate Treatment) Ipilimumab Q3wks x 4 started 1 day following the final dose of Sipuleucel-T (SipT).

SipT Treatment: All patients will receive standard of care SipT treatment every two weeks for a total of 3 treatments. The three treatments usually take about 30 days to complete.

SipT treatment is given in three 1 hour infusions. Each SipT treatment is generated from a standard blood cell-collection procedure (called leukapheresis) performed 2-3 days prior to the infusion.

Ipilimumab: Ipilimumab will be given by IV over 90 minutes every 3 weeks. Patients will be monitored during the infusion and up to 1 hour post-infusion.

Spots Global Cancer Trial Database for provenge

Every month we try and update this database with for provenge cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Multicenter Trial Enrolling Men With Advanced Prostate Cancer Who Are to Receive Combination Radiation and Sipuleucel-T	NCT02232230	Castrate Refrac...	Provenge	18 Years -	GenesisCare USA
PROvenge Treatment and Early Cancer Treatment	NCT00779402	Prostate Cancer	Control Sipuleucel-T	18 Years - 80 Years	Dendreon
Immune Monitoring on Sipuleucel-T	NCT02237170	Prostate Cancer		18 Years -	Icahn School of Medicine at Mount Sinai
Sipuleucel-T With Immediate vs. Delayed Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA-4) Blockade for Prostate Cancer	NCT01804465	Prostate Cancer	SipT Treatment Ipilimumab	18 Years -	University of California, San Francisco
A Multicenter Trial Enrolling Men With Advanced Prostate Cancer Who Are to Receive Combination Radiation and Sipuleucel-T	NCT02232230	Castrate Refrac...	Provenge	18 Years -	GenesisCare USA
Immune Monitoring on Sipuleucel-T	NCT02237170	Prostate Cancer		18 Years -	Icahn School of Medicine at Mount Sinai

Spots Global Cancer Trial Database for provenge

Every month we try and update this database with for provenge cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for provenge cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.