Description:
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.
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.
Completed
Phase 2
| Drug | Synonyms | Arms |
|---|---|---|
| SipT Treatment | Provenge | Delayed IpilimumabTreatment |
| Ipilimumab | BMS-734016/MDX-010, anti-CTLA4 | Delayed IpilimumabTreatment |
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.
| Name | Type | Description | Interventions |
|---|---|---|---|
| Immediate IpilimumabTreatment | Experimental | Arm 1 (Immediate Treatment) Ipilimumab Q3wks x 4 started 1 day following the final dose of SipT. |
|
| Delayed IpilimumabTreatment | Experimental | Arm 2 (Delayed Treatment) Ipilimumab Q3wks x 4 started 3 weeks following the final dose of SipT. |
|
Inclusion Criteria:
1. Histologically confirmed, metastatic prostate adenocarcinoma (positive bone scan
and/or measurable disease on CT scan and/or MRI of the abdomen and pelvis).
2. Progressive disease after androgen deprivation, as defined by Prostate Cancer Clinical
Trials Working Group 2 (PCWG2) and/or RECIST criteria. Patients must have disease
progression by one or both of the following:
- For patients with measurable disease, progression is defined as at least a 20%
increase in the sum of the longest diameter (LD) of target lesions or the
appearance of one or more new lesions, as per RECIST criteria version 1.1.
- For patients with no measurable disease, a positive bone scan and elevated
prostate specific antigen (PSA) will be required. PSA evidence for progressive
prostate cancer consists of a PSA level of at least 2 ng/milliliter (mL), which
has risen on at least 2 successive occasions, at least 1 week apart. If the
confirmatory PSA value is not greater than the screening PSA value, then an
additional test for rising PSA will be required to document progression.
- If no prior orchiectomy has been performed, patients must remain on luteinizing
hormone-releasing hormone (LHRH) agonist or antagonist (e.g. degarelix) therapy.
Patients who are receiving an antiandrogen as part of primary androgen ablation
must demonstrate disease progression following discontinuation of the
antiandrogen, defined as two consecutive rising PSA values, obtained at least two
weeks apart, or documented osseous or soft tissue progression. At least one of
the PSA values must be obtained at least four weeks (flutamide) or six weeks
(bicalutamide or nilutamide) after discontinuation.
3. Laboratory requirements:
- Absolute neutrophil count (ANC) ≥ 1500/μL
- Bilirubin < 1.5 x upper limit of normal (ULN)
- Hemoglobin ≥ 8 g/dL
- PSA ≥ 2 ng/mL
- Platelets ≥ 100,000/μL
- aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or
equal to 2.5 x ULN
- Creatinine clearance ≥ 60 mL/min by the Cockcroft Gault equation
- Testosterone less than or equal to 50 ng/dL
4. Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1 and life expectancy
≥ 12 weeks.
5. At least 18 years of age or older.
6. Patients receiving any other hormonal therapy, including any dose of megestrol acetate
(Megace), Proscar (finasteride), any herbal product known to decrease PSA levels (e.g.
Saw Palmetto, PC-SPES), or any systemic corticosteroid, must discontinue the agent for
at least four weeks prior to study treatment. Progressive disease as defined above
must be documented after discontinuation of any hormonal therapy (with the exception
of a LHRH agonist).
7. Prior radiation therapy must be completed ≥ 4 weeks prior to enrollment and the
patient must have recovered from all toxicity. Prior radiopharmaceuticals (strontium,
samarium) must be completed ≥ 8 weeks prior to enrollment.
8. Because of the unknown potential risk to a gamete and/or developing embryo from these
investigational therapies, patients must agree to use adequate contraception (barrier
method for males) for the duration of study participation, and for three months after
discontinuing therapy.
Exclusion Criteria:
1. Prior chemotherapy for prostate cancer, with the exception of neoadjuvant
chemotherapy, because of the potential effect of chemotherapy on the immune system.
2. Prior sipuleucel-T treatment or investigational immunotherapy.
3. Prostate cancer pain requiring regularly scheduled narcotics.
4. Current treatment with systemic steroid therapy (inhaled/topical steroids are
acceptable). Systemic corticosteroids must be discontinued for at least 4 weeks prior
to first treatment.
5. History of autoimmune disease including, but not limited to:
- Systemic lupus erythematosis (SLE), scleroderma, CREST syndrome, rheumatoid
arthritis
- Inflammatory bowel disease, celiac disease, primary biliary cirrhosis, autoimmune
hepatitis
- Dermatomyositis, polymyositis, giant cell arteritis
- Autoimmune hemolytic anemia (AIHA), cryoglobulinemia, antiphospholipid antibody
syndrome (APLS)
- Diabetes mellitus type I, myasthenia gravis, Grave's disease
- Wegener's granulomatosis or other vasculitis
- A history of Hashimoto's thyroiditis, psoriasis, or eczema, any of which has been
inactive for at least one year, or isolated Raynaud's phenomenon is acceptable
6. Known central nervous system or visceral metastases.
7. 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.
8. 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).
9. 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
10. Known HIV or other history of immunodeficiency disorder.
11. Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for
treatment of either a psychiatric or medical (e.g. infectious) illness.
12. Any underlying medical or psychiatric condition, which in the opinion of the
investigator will make the administration of ipilimumab hazardous or obscure the
interpretation of adverse events (AE), such as a condition associated with frequent
diarrhea.
13. A history of prior treatment with ipilimumab or prior cluster of differentiation 137
(CD137) agonist or CTLA-4 inhibitor or agonist.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | Male |
| Healthy Volunteers: | No |
| Measure: | Percentage of Participants With an Immune Response to Prostatic Acid Phosphatase (PAP) and/or PA2024 |
| Time Frame: | Up to 20 weeks |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Proportion of Patients Achieving a Prostate-specific Antigen (PSA) Decline of at Least 30% Below Baseline |
| Time Frame: | Up to 3 weeks |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Proportion of Patients Achieving a PSA Decline of at Least 50% Below Baseline |
| Time Frame: | Up to 3 weeks |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Proportion of Patients Achieving an Objective Response |
| Time Frame: | Up to 2 years |
| Safety Issue: | |
| Description: | 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 |
| Measure: | Proportion of Patients Achieving an Objective Response Stratified by Prior Radical Prostatectomy (RP) |
| Time Frame: | Up to 2 years |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Proportion of Patients Achieving an Objective Response Stratified by Radiation Therapy (RT) |
| Time Frame: | Up to 2 years |
| Safety Issue: | |
| Description: | 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 |
| Measure: | Radiographic Clinical Response Rate |
| Time Frame: | Up to 6 months |
| Safety Issue: | |
| Description: | 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 |
| Measure: | Median Time to PSA Progression |
| Time Frame: | Up to 12 weeks |
| Safety Issue: | |
| Description: | 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. |
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Completed |
| Lead Sponsor: | University of California, San Francisco |
August 18, 2021