Study of Sipuleucel-T W/ or W/O Radium-223 in Men With Asymptomatic or Minimally Symptomatic Bone-MCRPC

NCT02463799 | Completed Phase 2 Results DMC

• 2 other identifiers: J1522IRB00056435
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 5

Brief Summary

This clinical trial studies the effect of radium-223 when added to sipuleucel-T for treating castrate-resistant prostate cancer that has spread to the bone. Sipuleucel-T is an autologous cellular immunotherapy designed to stimulate an immune response against prostate cancer. It has been suggested that the immune response may be strengthened by radiation therapy. Therefore this study is testing whether radium-223 added to sipuleucel-T increases the immune response and anti-tumor effect against prostate cancer.

Conditions

Prostate Cancer

Keywords

prostatic neoplasms; castration-resistant; bone metastasis; radium-223; sipuleucel-T

Outcome Measures

Primary Outcomes (1)

• Immune Responses to Treatment With Sipuleucel-T (With or Without Radium-223) Measured by Peripheral PA2024 T-cell Proliferation

  Peripheral PA2024-specific T-cell proliferation responses using a 3H-thymidine incorporation assay at 6 weeks after the first dose of sipuleucel-T, measured by SI (Stimulation Index \[3H-thymidine incorporation in the presence of antigen divided by 3H-thymidine incorporation with media alone\] ).

  6 weeks

Secondary Outcomes (13)

• Peripheral PA2024 Specific T-cell Proliferation as Measured by Stimulation Index Over Time

  Up to 52 weeks

• Time to Radiographic or Clinical Progression

  Up to 2 years

• PSA50 Response (at Least a 50% Decline in PSA)

  Up to 2 years

• Peripheral PAP Specific T-cell Proliferation as Measured by Stimulation Index Over Time

  Up to 52 weeks

• Peripheral PA2024 Specific T-cell Activation

  Up to 52 weeks

Study Arms (2)

sipuleucel-T and radium 223 combination

EXPERIMENTAL

Radium-223 will be administered by intravenous injection over 1 minute at 50kbq (1.35 microcurie) per kg body weight per standard of care every 4 weeks at weeks 0, 4, 8, 12, 16, and 20 Sipuleucel-T will be administered intravenously per standard of care every 2 weeks at weeks 6, 8, and 10

Drug: Radium-223; Biological: Sipuleucel-T

sipuleucel-T alone

ACTIVE COMPARATOR

Sipuleucel-T will be administered intravenously per standard of care every 2 weeks at weeks 6, 8, and 10

Biological: Sipuleucel-T

Interventions

Radium-223 DRUG

6 infusions of radium-223 with 3 infusions of sipuleucel-T starting after second dose of radium-223

Also known as: Xofigo, BAY88-8223

sipuleucel-T and radium 223 combination

Sipuleucel-T BIOLOGICAL

3 infusions of sipuleucel-T alone

Also known as: Provenge

sipuleucel-T alone; sipuleucel-T and radium 223 combination

Eligibility Criteria

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

You may qualify if:

• Written informed consent provided prior to initiation of study procedures
• Age ≥ 18 years
• Histologically documented adenocarcinoma prostate cancer confirmed by a pathology report from prostate biopsy or a radical prostatectomy specimen. If prostatic tumor is of mixed histology, \> 50% of the tumor must be adenocarcinoma
• Bone metastases as manifested by one or more lesions on a bone scan performed within 2 months of screening
• Castrate-resistant prostate cancer, in the setting of castrate levels of testosterone (≤ 50 ng/dL), defined as current or historical evidence of disease progression concomitant with surgical castration or androgen deprivation therapy (ADT), as demonstrated by two consecutive rises in PSA OR new lesions on bone scan:
• PSA progression will be defined as 2 rising PSA values compared to a reference value, measured at least 7 days apart and the second value is ≥ 2 ng/mL \[1\]. It must be documented within 2 months of screening.
• Appearance of one or more new areas of abnormal uptake on bone scan when compared to imaging studies acquired during castration therapy or against the precastration studies if there was no response. Increased uptake of pre-existing lesions on bone scan does not constitute progression. It must be documented within 4 months of screening
• Serum PSA ≥ 2.0 ng/mL
• Screening ECOG perf status ≤ 1
• Asymptomatic or minimally symptomatic disease (no narcotic analgesic; other analgesics use is allowed)
• Prior abiraterone and enzalutamide are permitted, but not required
• Concurrent osteoclast-inhibitory therapies (zoledronic acid, denosumab) are permitted if patients have been on a stable dose for at least 1 month
• Adequate screening hematologic, renal, and liver function as evidenced by laboratory test results within the following ranges ≤ 28 days prior to registration:
• Absolute neutrophil count (ANC) ≥ 1.5 x109/L
• Platelet count ≥ 100 x109/L

You may not qualify if:

• The presence of known lung or liver metastases greater than 1.0 cm in the long axis diameter
• The presence of lymphadenopathy greater than 3 cm in the short-axis diameter
• The presence of known brain metastases
• Spinal cord compression, imminent long bone fracture, or any other condition that, in the opinion of the investigator, is likely to require radiation therapy and/or steroids for pain control during the active phase
• Previous treatment with chemotherapy for mCRPC (adjuvant chemotherapy is permitted), or chemotherapy for any reason within 2 years prior to registration
• Intention to receive chemotherapy within 6 months after enrollment in protocol therapy
• History of radiation therapy, either via external beam or brachytherapy within 28 days prior to registration
• Systemic radiotherapy with strontium-89, samarium-153, rhenium-186 or rhenium-188 for the treatment of bony metastases within previous 24 weeks
• Prior history of other cancers (except non-melanoma skin cancers or low-grade low-stage urothelial cancers)
• Use of prednisone or equivalent systemic corticosteroid within 2 weeks of treatment. Use of inhaled, intranasal, intra-articular, and topical steroids is allowed. Oral or IV steroids to prevent or treat IV contrast reactions are allowed
• Use of opioid analgesics for cancer-related pain
• Use of experimental drug within 4 weeks of treatment
• Uncontrolled medical conditions including diabetes, heart failure, COPD, ulcerative colitis, or Crohn's disease
• Uncontrolled fecal incontinence
• Any medical intervention, any other condition, or any other circumstance which, in the opinion of the investigator, could compromise adherence with study requirements or otherwise compromise the study's objectives

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Dendreon: collaborator
• Bayer: collaborator

Study Sites (5)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Sibley Memorial Hospital

Washington D.C., District of Columbia, 20016, United States

Location

Tulane Cancer Center

New Orleans, Louisiana, 70112, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21231, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Related Publications (2)

• Marshall CH, Fu W, Wang H, Park JC, DeWeese TL, Tran PT, Song DY, King S, Afful M, Hurrelbrink J, Manogue C, Cotogno P, Moldawer NP, Barata PC, Drake CG, Posadas EM, Armstrong AJ, Sartor O, Antonarakis ES. Randomized Phase II Trial of Sipuleucel-T with or without Radium-223 in Men with Bone-metastatic Castration-resistant Prostate Cancer. Clin Cancer Res. 2021 Mar 15;27(6):1623-1630. doi: 10.1158/1078-0432.CCR-20-4476. Epub 2021 Jan 15.

  PMID: 33451978 RESULT

• Gongora ABL, Marshall CH, Velho PI, Lopes CDH, Marin JF, Camargo AA, Bastos DA, Antonarakis ES. Extreme Responses to a Combination of DNA-Damaging Therapy and Immunotherapy in CDK12-Altered Metastatic Castration-Resistant Prostate Cancer: A Potential Therapeutic Vulnerability. Clin Genitourin Cancer. 2022 Apr;20(2):183-188. doi: 10.1016/j.clgc.2021.11.015. Epub 2021 Dec 24. No abstract available.

  PMID: 35027313 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Radium-223; radium Ra 223 dichloride; sipuleucel-T

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Emmanuel Antonarakis, MD
• Organization: Johns Hopkins University

eantona1@jhmi.edu

410-502-8341

Study Officials

• Emmanuel Antonarakis, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: May 21, 2015
• First Posted: June 4, 2015
• Study Start: February 22, 2016
• Primary Completion: December 12, 2019
• Study Completion: December 12, 2019
• Last Updated: July 8, 2021
• Results First Posted: July 8, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)