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

NCT01804465 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 12557NCI-2014-00318
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

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.

Conditions

Prostate Cancer

Keywords

castration resistant; prostate; cancer; ipilimumab; provenge; SipT

Outcome Measures

Primary Outcomes (2)

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

  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.

  Up to 20 weeks

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

  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.

  Up to 20 weeks

Secondary Outcomes (7)

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

  Up to 3 weeks

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

  Up to 3 weeks

• Proportion of Patients Achieving an Objective Response

  Up to 2 years

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

  Up to 2 years

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

  Up to 2 years

Study Arms (2)

Immediate IpilimumabTreatment

EXPERIMENTAL

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

Drug: SipT Treatment; Drug: Ipilimumab

Delayed IpilimumabTreatment

EXPERIMENTAL

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

Drug: SipT Treatment; Drug: Ipilimumab

Interventions

SipT Treatment DRUG

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.

Also known as: Provenge

Delayed IpilimumabTreatment; Immediate IpilimumabTreatment

Ipilimumab DRUG

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.

Also known as: BMS-734016/MDX-010, anti-CTLA4

Delayed IpilimumabTreatment; Immediate IpilimumabTreatment

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed, metastatic prostate adenocarcinoma (positive bone scan and/or measurable disease on CT scan and/or MRI of the abdomen and pelvis).
• 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.
• 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
• Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1 and life expectancy ≥ 12 weeks.

You may not qualify if:

• Prior chemotherapy for prostate cancer, with the exception of neoadjuvant chemotherapy, because of the potential effect of chemotherapy on the immune system.
• Prior sipuleucel-T treatment or investigational immunotherapy.
• Prostate cancer pain requiring regularly scheduled narcotics.
• 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.
• 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
• Known central nervous system or visceral metastases.
• 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).

Sponsors & Collaborators

• University of California, San Francisco: lead
• M.D. Anderson Cancer Center: collaborator
• Bristol-Myers Squibb: collaborator
• Dendreon: collaborator

Study Sites (2)

University of California San Francisco

San Francisco, California, 94115, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Sinha M, Zhang L, Subudhi S, Chen B, Marquez J, Liu EV, Allaire K, Cheung A, Ng S, Nguyen C, Friedlander TW, Aggarwal R, Spitzer M, Allison JP, Small EJ, Sharma P, Fong L. Pre-existing immune status associated with response to combination of sipuleucel-T and ipilimumab in patients with metastatic castration-resistant prostate cancer. J Immunother Cancer. 2021 May;9(5):e002254. doi: 10.1136/jitc-2020-002254.

  PMID: 33986125 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms; Neoplasms

Interventions

sipuleucel-T; Ipilimumab

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Lawrence Fong, MD
• Organization: University of California, San Francisco

Lawrence.Fong@ucsf.edu

(415) 514-3160

Study Officials

• Lawrence Fong, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Padmanee Sharma, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2013
• First Posted: March 5, 2013
• Study Start: April 22, 2014
• Primary Completion: February 27, 2020
• Study Completion: August 31, 2020
• Last Updated: August 18, 2021
• Results First Posted: January 25, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)