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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01804465
Recruitment Status : Active, not recruiting
First Posted : March 5, 2013
Last Update Posted : April 30, 2020
Sponsor:
Collaborators:
M.D. Anderson Cancer Center
Bristol-Myers Squibb
Dendreon
Information provided by (Responsible Party):
University of California, San Francisco

Tracking Information
First Submitted Date  ICMJE February 27, 2013
First Posted Date  ICMJE March 5, 2013
Last Update Posted Date April 30, 2020
Actual Study Start Date  ICMJE April 22, 2014
Actual Primary Completion Date February 27, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 24, 2019)
  • Frequency of observing an immune response to prostatic acid phosphatase (PAP) and/or PA2024 [ Time Frame: Up to 20 weeks ]
    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 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 primary hypothesis is tested by comparing the proportion of patients achieving an IgG immune response to PAP or PA2024 to the null hypothesis of 15% (based off an observed anti-PAP IgG response rate of 17.7% seen at a similar time interval in patients treated w/ sipuleucel-T. The same single sample test will be performed for IgM antibodies. The positive immune proportion for both IgG and IgM antibodies to PAP and to PA2024 with 95% confidence intervals will be used to summarize the results for each study arm.
  • Frequency of highest grade toxicity [ Time Frame: up to 3 weeks ]
    Toxicities will be reported for each study arm at each dose of ipilimumab administered with descriptive statistics (e.g. proportions) by tabulating the frequency of the maximum grade occurring for each patient for each type using NCI Common Terminology Criteria for Adverse Events (CTCAE) v. 4.0 criteria. As described above the type and grade of all such Immune Response Adverse Events (IRAEs) will be tabulated by treatment arm. Toxicity results will be presented indicating occurrences during the first 20 weeks of protocol therapy and those occurring later.
Original Primary Outcome Measures  ICMJE
 (submitted: March 4, 2013)
  • Safety assessment of combining ipilimumab with SipT [ Time Frame: Up to 3 weeks ]
    To assess the safety of immediate sequential vs. delayed sequential ipilimumab following SipT.
  • Impact of the timing of ipilimumab administration on PAP/PA2024specific immune responses by SipT [ Time Frame: Up to 20 weeks ]
    To assess the impact of the timing of ipilimumab treatment on the induction of IG antibody repsonses by SipT, the proportion of patients on each study arm who achieve an immune response to PAP and/or PA2024at study week 20 will be determined.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 24, 2019)
  • Prostate Specific Antigen (PSA) response rate [ Time Frame: Up to 3 weeks ]
    Descriptive statistics will be calculated to characterize the proportion of patients achieving a PSA decline of at least >30% and >50% and presented along with the 95% confidence intervals for each study arm. The proportion of patients achieving an objective response will also be determined. Descriptive statistics will be presented for each study arm to summarize response according to important disease features such as lactate dehydrogenase (LDH) (abnormal vs. normal) and prior treatment (radiation therapy, radical prostatectomy (RP), systemic steroid usage > 3 months).
  • Time to PSA progression [ Time Frame: Up to 2 years ]
    Descriptive statistics will be used to summarize time to PSA progression. The Kaplan-Meier product limit will be used to estimate the probability of time to PSA progression with durations measured from the start of protocol therapy. For each study arm the median time to progression with 95% confidence intervals will be presented to summarize clinical efficacy.
  • Radiographic Clinical Response Rate [ Time Frame: Up to 6 months ]
    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
Original Secondary Outcome Measures  ICMJE
 (submitted: March 4, 2013)
  • Prostate Specific Antigen (PSA) Measurements (patient response to therapy) [ Time Frame: Up to 3 weeks ]
    Patient response in this study is defined as a PSA decline
  • Radiographic Clinical Responses [ Time Frame: Up to 6 months ]
  • Modulation of Effector and Regulatory T Cells [ Time Frame: Up to 20 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: March 4, 2013)
  • Circulating Tumor Cells (CTC) [ Time Frame: Up to 16 weeks ]
  • T Cell Gene and MicroRNA Signatures [ Time Frame: Up to 20 weeks ]
    Descriptive statistics will be calculated to summarize the change in T cell signaling pathways in addition to the change in gene expression and microRNAs with therapy over time.
 
Descriptive Information
Brief Title  ICMJE Sipuleucel-T With Immediate vs. Delayed Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA-4) Blockade for Prostate Cancer
Official Title  ICMJE A Randomized Phase 2 Trial of Immediate vs. Delayed Anti-CTLA4 Blockade Following Sipuleucel-T Treatment for Prostate Cancer Immunotherapy
Brief Summary 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.
Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Prostate Cancer
Intervention  ICMJE
  • Drug: 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.

    Other Name: Provenge
  • Drug: 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.
    Other Name: BMS-734016/MDX-010, anti-CTLA4
Study Arms  ICMJE
  • Experimental: Immediate IpilimumabTreatment
    Arm 1 (Immediate Treatment) Ipilimumab Q3wks x 4 started 1 day following the final dose of SipT.
    Interventions:
    • Drug: SipT Treatment
    • Drug: Ipilimumab
  • Experimental: Delayed IpilimumabTreatment
    Arm 2 (Delayed Treatment) Ipilimumab Q3wks x 4 started 3 weeks following the final dose of SipT.
    Interventions:
    • Drug: SipT Treatment
    • Drug: Ipilimumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: October 14, 2019)
50
Original Estimated Enrollment  ICMJE
 (submitted: March 4, 2013)
66
Estimated Study Completion Date  ICMJE October 31, 2021
Actual Primary Completion Date February 27, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 PSA Working Group 2 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 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 AEs, 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01804465
Other Study ID Numbers  ICMJE 12557
NCI-2014-00318 ( Registry Identifier: NCI Clinical Trials Reporting Program (CTRP) )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University of California, San Francisco
Study Sponsor  ICMJE University of California, San Francisco
Collaborators  ICMJE
  • M.D. Anderson Cancer Center
  • Bristol-Myers Squibb
  • Dendreon
Investigators  ICMJE
Principal Investigator: Lawrence Fong, MD University of California, San Francisco
Principal Investigator: Padmanee Sharma, MD The University of Texas MD Anderson Cancer Center
PRS Account University of California, San Francisco
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP