Castration Levels of Testosterone, Castration-Resistant Prostate Carcinoma, Metastatic Prostate Carcinoma, Stage IV Prostate Cancer
Conditions
Brief summary
This randomized phase II trial studies how well glycosylated recombinant human interleukin-7 (CYT107) after vaccine therapy works in treating patients with castration-resistant prostate cancer that has spread to other areas of the body or has not responded to at least one type of treatment. Biological therapies, such as glycosylated recombinant human interleukin-7, may stimulate the immune system in different ways and stop tumor cells from growing. Vaccines made from white blood cells mixed with tumor proteins may help the body build an effective immune response to kill tumor cells. It is not yet known whether glycosylated recombinant human interleukin-7 works better with or without vaccine therapy in treating prostate cancer.
Detailed description
PRIMARY OBJECTIVES: I. To determine whether CYT107 administration increases the vaccine-induced antigen-specific T-cell immune response to the sipuleucel-T fusion protein vaccine construct prostatic acid phosphatase granulocyte-macrophage colony-stimulating factor (PAP-GM-CSF) (PA2024). SECONDARY OBJECTIVES: I. To determine whether CYT107 administration increases the vaccine-induced antigen-specific T-cell immune response to PAP. II. To assess the character of the T-cell immune response to PAP and PA2024. III. To determine whether CYT107 administration increases the vaccine-induced antigen-specific antibody immune responses to PAP and PA2024. IV. To quantify the effects of CYT107 on T-cell repertoire diversity. V. To assess the effects of CYT107 on the immune competence of patients with advanced prostate cancer. VI. To assess the clinical efficacy and tolerability of sipuleucel-T plus CYT107 compared with sipuleucel-T alone. OUTLINE: Patients are randomized to 1 of 2 cohorts. COHORT I: Patients receive no treatment (observation) after completion of standard sipuleucel-T therapy. COHORT II: Patients receive glycosylated recombinant human interleukin-7 subcutaneously (SC) every week for 4 weeks (on days 0, 7, 14, and 21) beginning 3-7 days after completion of standard sipuleucel-T therapy. Treatment continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 53 weeks. Patients are followed by phone, once a year, after completion of Week 53 for overall survival.
Interventions
Given SC
OTHERLaboratory Biomarker Analysis
Correlative studies
Sponsors
Cancer Immunotherapy Trials Network
National Cancer Institute (NCI)
Fred Hutchinson Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC) * Patients must have successfully completed therapy with sipuleucel-T within 3-7 days of planned CYT107 study drug treatment * Assessable disease with a positive bone scan and/or measurable disease on computed tomography (CT) scan and/or magnetic resonance imaging (MRI) of the abdomen and pelvis * Prior orchiectomy or must be on ongoing luteinizing hormone-releasing hormone (LHRH) agonist or antagonist (e.g., degarelix) therapy * No ongoing anti-androgen therapy; patients must be off anti-androgen therapy for at least 30 days * Patients receiving any other hormonal therapy, including any dose of megestrol acetate (Megace), Proscar (finasteride), any herbal product known to decrease prostate specific antigen (PSA) levels (e.g. saw palmetto, PC-SPES), or any systemic corticosteroid, must discontinue the agent for at least 30 days prior to study treatment * Absolute neutrophil count (ANC) \>= 1500/uL * Bilirubin \< 1.5 x upper limit of normal (ULN) * Hemoglobin \>= 10 g/dL * Platelets \>= 100,000/mcL * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x ULN * Creatinine clearance \>= 60 mL/min by the Cockcroft-Gault equation * Testosterone =\< 50 ng/dL (documented at any time while on LHRH agonist or antagonists or s/p orchiectomy) * Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 or a Karnofsky performance status of \>= 80% * Life expectancy of at least 6 months * Prior local radiation therapy must be completed at least 30 days prior to enrollment and the patient must have recovered from all toxicity * Prior systemic radiopharmaceuticals (strontium, samarium, radium 223 dichloride) must be completed \>= 8 weeks prior to enrollment * Patients must agree to use 2 methods of adequate contraception for the duration of study participation, and for four months after discontinuing therapy * Ability to understand and the willingness to sign a written informed consent document
Exclusion criteria
* Prior chemotherapy for castration resistant prostate cancer; neoadjuvant chemotherapy and chemotherapy given for hormone sensitive prostate cancer are allowed * Prior investigational immunotherapy * Prostate cancer pain requiring regularly scheduled narcotics * Pathologic long-bone fractures, imminent pathologic long-bone fracture (cortical erosion on radiography \> 50%) or spinal cord compression * Current treatment with systemic steroid therapy (inhaled/topical steroids are acceptable); systemic corticosteroids must be discontinued for at least 30 days prior to first CYT107 injection * Known central nervous system metastases * Documented cirrhosis or documented acute hepatitis; Note: a positive hepatitis B serology indicative of previous immunization (i.e., hepatitis B surface antibody \[HBsAb\] positive and hepatitis B core antibody \[HBcAb\] negative), or a fully resolved acute hepatitis B virus (HBV) infection is not an exclusion criterion * History of severe asthma, as defined by prior or current use of systemic corticosteroids for disease control, with the exception of physiological replacement doses of cortisone acetate or equivalent, as defined by a dose of 10 mg or less * Medical or psychiatric illness that would, in the opinion of the investigator, preclude participation in the study or the ability of patients to provide informed consent for themselves * Cardiovascular disease that meets one of the following: congestive heart failure (New York Heart Association class III or IV), active angina pectoris, or recent myocardial infarction (within the last 6 months) * Concurrent or prior malignancy except for the following: * Adequately treated basal or squamous cell skin cancer * Adequately treated stage I or II cancer from which the patient is currently in complete remission * Any other cancer from which the patient has been disease-free for 5 years * Known human immunodeficiency virus (HIV) or other history of immunodeficiency disorder; HIV-positive patients on combination antiretroviral therapy are ineligible * Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or medical (e.g. infectious) illness * Any underlying medical or psychiatric condition, which in the opinion of the investigator will make the administration of CYT107 hazardous or obscure the interpretation of adverse events (AEs), such as a condition associated with frequent diarrhea * History of allergic reactions attributed to compounds of similar chemical or biologic composition to CYT107 * Patients who have received prior immunosuppressive therapy within 30 days prior to enrollment * Active (as defined by requiring immunosuppressive therapy) or history of clinically significant autoimmune disease (as defined by previously requiring immunosuppressive therapy) * Patients who have received hepatotoxic drugs less than 7 days prior to enrollment * Patients who have received prior biologic agents less than 30 days prior to enrollment * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * Patients who have a history of any hematopoietic malignancy * History of pulmonary disease such as emphysema or chronic obstructive pulmonary disease (COPD), (forced expiratory volume \[FEV\] \> 60% of predicted for height and age required in patients with prolonged smoking history or symptoms of respiratory dysfunction)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Quantification of T-cell Responses to Prostatic Acid Phosphatase Granulocyte-macrophage Colony-stimulating Factor (PAP-GM-CSF), Assessed by Quantification of Interferon Gamma Levels Measured Using Enzyme-linked Immunospot (ELISPOT) | Day 70 (week 11) | The Mann-Whitney-Wilcoxon (MWW) test will be used as part of the statistical analysis to determine quantification of T-cell responses to prostatic acid phosphatase granulocyte-macrophage colony-stimulating factor (PAP-GM-CSF), as assessed by quantification of interferon gamma levels measured using enzyme-linked immunospot (ELISPOT). The power is roughly equivalent to that based on the t-test. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Circulating Tumor Cells | Baseline to up to week 53 | Enumerated by the approved Veridex assay. |
| Change in Number of Peripheral Blood Mononuclear Cell (PBMC) Subsets and T Lymphocyte Subsets | Week 11 | The absolute fold change from baseline of CD3+ cells |
| Change in Bystander Antigen Specific Immune Responses, Measured by Interferon Gamma Production in Response to Various Antigens as Quantified by Enzyme-linked Immunospot (ELISPOT) | Baseline to up to week 53 | Bystander antigen specific immune responses will be assessed to other ongoing and nascent antitumor responses (e.g., preferentially expressed antigen in melanoma, cancer/testis antigen 1B and/or tumor protein p53), additional tumor antigens specific to prostate cancer (e.g., prostate specific antigen \[PSA\] and/or prostate-specific membrane antigen), and memory viral responses (influenza A and cytomegalovirus, Epstein-Barr virus and influenza virus-derived peptides) using the interferon gamma ELISPOT assay. |
| Change in Vaccine-induced Antigen-specific Antibody Immune Response to Prostatic Acid Phosphatase (PAP) | Baseline to up to week 6 | Will be measured by change in immunoglobulin G (IgG) and immunoglobulin M (IgM) levels quantified by standard enzyme-linked immunosorbent assay (ELISA). Fold change from baseline in week 6 titer |
| Overall Survival | Up to 5 years | Number of participants that have survived |
| Change in Prostate Specific Antigen (PSA) Kinetics. | Baseline to up to week 53 | The change in prostate specific antigen (PSA) kinetics will be evaluated according to the recommendations from PSA Working Group (PSAWG). Analysis of PSA doubling time |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort I (no Therapy) Patients receive no treatment (observation) after completion of standard sipuleucel-T therapy. | 26 |
| Cohort II (Glycosylated Recombinant Human Interleukin-7) Patients receive glycosylated recombinant human interleukin-7 SC every week for 4 weeks (on days 0, 7, 14, and 21) beginning 3-7 days after completion of standard sipuleucel-T therapy. Treatment continues in the absence of disease progression or unacceptable toxicity.
Glycosylated Recombinant Human Interleukin-7: Given SC
Laboratory Biomarker Analysis: Correlative studies | 28 |
| Total | 54 |
Baseline characteristics
| Characteristic | Total | Cohort I (no Therapy) | Cohort II (Glycosylated Recombinant Human Interleukin-7) |
|---|---|---|---|
| Age, Continuous | 66.9 years STANDARD_DEVIATION 7.7 | 66.1 years STANDARD_DEVIATION 7.6 | 67.6 years STANDARD_DEVIATION 7.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 51 Participants | 25 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 2 Participants |
| Region of Enrollment United States | 54 Participants | 26 Participants | 28 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 54 Participants | 26 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 26 | 3 / 28 |
| other Total, other adverse events | 26 / 26 | 28 / 28 |
| serious Total, serious adverse events | 2 / 26 | 8 / 28 |
Outcome results
Primary
Quantification of T-cell Responses to Prostatic Acid Phosphatase Granulocyte-macrophage Colony-stimulating Factor (PAP-GM-CSF), Assessed by Quantification of Interferon Gamma Levels Measured Using Enzyme-linked Immunospot (ELISPOT)
The Mann-Whitney-Wilcoxon (MWW) test will be used as part of the statistical analysis to determine quantification of T-cell responses to prostatic acid phosphatase granulocyte-macrophage colony-stimulating factor (PAP-GM-CSF), as assessed by quantification of interferon gamma levels measured using enzyme-linked immunospot (ELISPOT). The power is roughly equivalent to that based on the t-test.
Time frame: Day 70 (week 11)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort I (no Therapy) | Quantification of T-cell Responses to Prostatic Acid Phosphatase Granulocyte-macrophage Colony-stimulating Factor (PAP-GM-CSF), Assessed by Quantification of Interferon Gamma Levels Measured Using Enzyme-linked Immunospot (ELISPOT) | 212.2 T cell spots per 300,000 PBMC | Standard Deviation 111.97 |
| Cohort II (Glycosylated Recombinant Human Interleukin-7) | Quantification of T-cell Responses to Prostatic Acid Phosphatase Granulocyte-macrophage Colony-stimulating Factor (PAP-GM-CSF), Assessed by Quantification of Interferon Gamma Levels Measured Using Enzyme-linked Immunospot (ELISPOT) | 199.68 T cell spots per 300,000 PBMC | Standard Deviation 182.4 |
Secondary
Change in Bystander Antigen Specific Immune Responses, Measured by Interferon Gamma Production in Response to Various Antigens as Quantified by Enzyme-linked Immunospot (ELISPOT)
Bystander antigen specific immune responses will be assessed to other ongoing and nascent antitumor responses (e.g., preferentially expressed antigen in melanoma, cancer/testis antigen 1B and/or tumor protein p53), additional tumor antigens specific to prostate cancer (e.g., prostate specific antigen \[PSA\] and/or prostate-specific membrane antigen), and memory viral responses (influenza A and cytomegalovirus, Epstein-Barr virus and influenza virus-derived peptides) using the interferon gamma ELISPOT assay.
Time frame: Baseline to up to week 53
Population: No subjects were tested for bystander antigen specific immune responses because there was no indication that there was an enhanced response in the primary objective.
Secondary
Change in Circulating Tumor Cells
Enumerated by the approved Veridex assay.
Time frame: Baseline to up to week 53
Population: Cohort 1: 16 subjects analyzed at Week 01 and 8 subjects analyzed at Week 53. Cohort 2: 22 subjects analyzed at Week 01 and 5 subjects analyzed at Week 53.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort I (no Therapy) | Change in Circulating Tumor Cells | Week 01 | 2.56 Circulating Tumor Cells | Standard Deviation 7.88 |
| Cohort I (no Therapy) | Change in Circulating Tumor Cells | Week 53 | 2.63 Circulating Tumor Cells | Standard Deviation 5.97 |
| Cohort II (Glycosylated Recombinant Human Interleukin-7) | Change in Circulating Tumor Cells | Week 01 | 1.45 Circulating Tumor Cells | Standard Deviation 2.97 |
| Cohort II (Glycosylated Recombinant Human Interleukin-7) | Change in Circulating Tumor Cells | Week 53 | 0 Circulating Tumor Cells | Standard Deviation 0 |
Secondary
Change in Number of Peripheral Blood Mononuclear Cell (PBMC) Subsets and T Lymphocyte Subsets
The absolute fold change from baseline of CD3+ cells
Time frame: Week 11
Population: Subjects for whom whole blood was collected at protocol specified timepoints
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort I (no Therapy) | Change in Number of Peripheral Blood Mononuclear Cell (PBMC) Subsets and T Lymphocyte Subsets | Week 06 | 1.05 fold change | Standard Deviation 0.29 |
| Cohort I (no Therapy) | Change in Number of Peripheral Blood Mononuclear Cell (PBMC) Subsets and T Lymphocyte Subsets | Week 11 | 1.21 fold change | Standard Deviation 0.34 |
| Cohort II (Glycosylated Recombinant Human Interleukin-7) | Change in Number of Peripheral Blood Mononuclear Cell (PBMC) Subsets and T Lymphocyte Subsets | Week 06 | 2.33 fold change | Standard Deviation 1.02 |
| Cohort II (Glycosylated Recombinant Human Interleukin-7) | Change in Number of Peripheral Blood Mononuclear Cell (PBMC) Subsets and T Lymphocyte Subsets | Week 11 | 1.77 fold change | Standard Deviation 0.55 |
Secondary
Change in Prostate Specific Antigen (PSA) Kinetics.
The change in prostate specific antigen (PSA) kinetics will be evaluated according to the recommendations from PSA Working Group (PSAWG). Analysis of PSA doubling time
Time frame: Baseline to up to week 53
Population: Study participants who provided blood for PSA testing and analysis
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cohort I (no Therapy) | Change in Prostate Specific Antigen (PSA) Kinetics. | 46.82 Weeks |
| Cohort II (Glycosylated Recombinant Human Interleukin-7) | Change in Prostate Specific Antigen (PSA) Kinetics. | 8.15 Weeks |
Secondary
Change in Vaccine-induced Antigen-specific Antibody Immune Response to Prostatic Acid Phosphatase (PAP)
Will be measured by change in immunoglobulin G (IgG) and immunoglobulin M (IgM) levels quantified by standard enzyme-linked immunosorbent assay (ELISA). Fold change from baseline in week 6 titer
Time frame: Baseline to up to week 6
Population: Participants who provided blood samples to test for antibody levels to PAP
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort I (no Therapy) | Change in Vaccine-induced Antigen-specific Antibody Immune Response to Prostatic Acid Phosphatase (PAP) | IgG-IgM levels | 8 fold change |
| Cohort I (no Therapy) | Change in Vaccine-induced Antigen-specific Antibody Immune Response to Prostatic Acid Phosphatase (PAP) | IgG levels | 4 fold change |
| Cohort II (Glycosylated Recombinant Human Interleukin-7) | Change in Vaccine-induced Antigen-specific Antibody Immune Response to Prostatic Acid Phosphatase (PAP) | IgG-IgM levels | 8 fold change |
| Cohort II (Glycosylated Recombinant Human Interleukin-7) | Change in Vaccine-induced Antigen-specific Antibody Immune Response to Prostatic Acid Phosphatase (PAP) | IgG levels | 2 fold change |
Secondary
Overall Survival
Number of participants that have survived
Time frame: Up to 5 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort I (no Therapy) | Overall Survival | 22 Participants |
| Cohort II (Glycosylated Recombinant Human Interleukin-7) | Overall Survival | 25 Participants |