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

NCT ID: NCT02463799

Last Updated: 2021-07-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-02-22
• Study Completion Date: 2019-12-12

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.

Detailed Description

This is a randomized study designed to assess the antigen-specific immune response of sipuleucel-T with or without radium-223. Eligible subjects will be registered and randomly assigned in a 1:1 ratio to receive sipuleucel-T and radium-223 or sipuleucel-T alone.

Subjects in both arms (sipuleucel-T and radium) will undergo a standard 1.5 to 2.0 blood volume leukapheresis, followed approximately 3 days later by an IV infusion of sipuleucel-T. This process will occur a total of 3 times at approximately 2-week intervals. Subjects in Arm 1 will receive a total of 6 infusions of radium-223 at IV dose of 50 kBq/kg at 4-week interval.

All participants are allowed to receive the best supportive care which includes secondary hormonal manipulation as required. No chemotherapy, external-beam radiation, or other radionuclides are allowed while on active treatment but are permitted after completion of active treatment. Glucocorticoid-containing treatments should be minimized to less than the equivalent dose of prednisone 10mg daily if feasible for the 3 months following sipuleucel-T therapy. All patients continue medical or surgical castration during treatment.

Conditions

Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

sipuleucel-T and radium 223 combination

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

Group Type: EXPERIMENTAL

Radium-223

Intervention Type: DRUG

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

Sipuleucel-T

Intervention Type: BIOLOGICAL

3 infusions of sipuleucel-T alone

sipuleucel-T alone

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

Group Type: ACTIVE_COMPARATOR

Sipuleucel-T

Intervention Type: BIOLOGICAL

3 infusions of sipuleucel-T alone

Interventions

Radium-223

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

Intervention Type: DRUG

Sipuleucel-T

3 infusions of sipuleucel-T alone

Intervention Type: BIOLOGICAL

Other Intervention Names

Xofigo, BAY88-8223; Provenge

Eligibility Criteria

Inclusion Criteria

1. Written informed consent provided prior to initiation of study procedures

2. Age ≥ 18 years

3. 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

4. Bone metastases as manifested by one or more lesions on a bone scan performed within 2 months of screening

5. 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

6. Serum PSA ≥ 2.0 ng/mL

7. Screening ECOG perf status ≤ 1

8. Asymptomatic or minimally symptomatic disease (no narcotic analgesic; other analgesics use is allowed)

9. Prior abiraterone and enzalutamide are permitted, but not required

10. Concurrent osteoclast-inhibitory therapies (zoledronic acid, denosumab) are permitted if patients have been on a stable dose for at least 1 month

11. 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
• Hemoglobin ≥ 10.0 g/dL
• Total bilirubin level ≤ 1.5 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
• Creatinine ≤ 1.5 x ULN
• Albumin > 25 g/L

Exclusion Criteria

1. The presence of known lung or liver metastases greater than 1.0 cm in the long axis diameter

2. The presence of lymphadenopathy greater than 3 cm in the short-axis diameter

3. The presence of known brain metastases

4. 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

5. Previous treatment with chemotherapy for mCRPC (adjuvant chemotherapy is permitted), or chemotherapy for any reason within 2 years prior to registration

6. Intention to receive chemotherapy within 6 months after enrollment in protocol therapy

7. History of radiation therapy, either via external beam or brachytherapy within 28 days prior to registration

8. Systemic radiotherapy with strontium-89, samarium-153, rhenium-186 or rhenium-188 for the treatment of bony metastases within previous 24 weeks

9. Prior history of other cancers (except non-melanoma skin cancers or low-grade low-stage urothelial cancers)

10. 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

11. Use of opioid analgesics for cancer-related pain

12. Use of experimental drug within 4 weeks of treatment

13. Uncontrolled medical conditions including diabetes, heart failure, COPD, ulcerative colitis, or Crohn's disease

14. Uncontrolled fecal incontinence

15. 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Dendreon

INDUSTRY

Sponsor Role: collaborator

Bayer

INDUSTRY

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Emmanuel Antonarakis, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

Cedars-Sinai Medical Center

Los Angeles, California, United States

Sibley Memorial Hospital

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

Tulane Cancer Center

New Orleans, Louisiana, United States

Johns Hopkins Hospital

Baltimore, Maryland, United States

Duke University

Durham, North Carolina, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 33451978 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35027313 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

IRB00056435

Identifier Type: OTHER

Identifier Source: secondary_id

J1522

Identifier Type: -

Identifier Source: org_study_id