Study Evaluating the Addition of Pembrolizumab to Radium-223 in mCRPC

NCT03093428 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 16-498
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 2

Brief Summary

This research study is studying the safety and tolerability of an investigational combination of drugs, radium-223 plus pembrolizumab as a possible treatment for castration-resistant prostate cancer. The interventions involved in this study are:

• Radium-223
• Pembrolizumab

Conditions

Prostate Cancer

Keywords

Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Increased Immune Cell Infiltration Across Arms

  Differences in immune infiltrating cells (CD8+ T-cells and CD4+ T-cells) in bone biopsy specimens were compared from baseline to 8 weeks on study therapy between the treatment arms.

  2 months

Secondary Outcomes (3)

• Number of Participants With Grade 3 or Higher Treatment Related Adverse Events

  Toxicity was assessed every cycle and up to 22.4 months.

• Median Progression-Free Survival

  Imaging was performed every 12 weeks and up to 25 months.

• Median Overall Survival

  Participants were followed up for ~36 months.

Study Arms (2)

Pembrolizumab Plus Radium-223

EXPERIMENTAL

* Radium-223 will be administered intravenously every 4 weeks at a pre-determined dose * Pembrolizumab will be administered intravenously every 3 weeks at a pre-determined dose Radium-223 will be halted after 3 doses. Once radiographic progressive disease occurs, the last 3 doses of radium will be given.

Drug: Radium-223; Drug: Pembrolizumab

Radium-223

EXPERIMENTAL

\- Radium-223 will be administered intravenously every 4 weeks at a pre-determined dose

Drug: Radium-223

Interventions

Radium-223 DRUG

Radium-223 is a calcium mimetic that hones in on bone metastases. It binds to new bone stroma and emits alpha particles, which induce double-stranded DNA breaks that result in tumor cell death.

Also known as: Xofigo

Pembrolizumab Plus Radium-223; Radium-223

Pembrolizumab DRUG

Pembrolizumab is a PD-1 inhibitor. Pembrolizumab binds to human PD-1 and blocks the interaction between PD1 and its ligands.

Also known as: Keytruda

Pembrolizumab Plus Radium-223

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed adenocarcinoma of the prostate
• Castration-resistant prostate cancer requires the following 3 criteria:
• Progression after surgical castration or on GnRH agonist or antagonist
• A castrate level of testosterone (\<50ng/dL)
• Prostate cancer progression documented by PSA rise or bone progression according to PCWG2
• There is no limit to number of prior therapies
• Metastatic disease by bone scan
• Age ≥18 years
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Be willing to undergo a core or excisional biopsy of a bone metastasis prior to study drug initiation for tumor tissue. Newly-obtained is defined as a specimen obtained up to 12 weeks (84 days) prior to initiation of treatment on Day 1. Bone biopsy can have been done prior to screening; archival specimens of bone metastasis are permitted if done for other purpose and available.
• If biopsy is non-diagnostic, patient must undergo repeat biopsy as proof of tumor tissue by pathology review. Proof of tumor specimen is required for eligibility.
• Be willing to undergo a second core or excisional biopsy of a bone metastasis on therapy (approximately after 8 weeks of study therapy or after 2 doses of radium-223 if delays have occurred).
• Demonstrate adequate organ function as defined below, all screening labs for eligibility should be performed within 30 days prior to treatment initiation.
• Hematological
• Absolute neutrophil count (ANC) ≥ 1,500 /mcL

You may not qualify if:

• Pathology consistent with majority of specimen having small cell carcinoma of the prostate (prostate cancer with other neuroendocrine features is acceptable).
• Prior treatment with radium-223
• Prior treatment with a PD-1, PD-L1, or PD-L2 blocking therapy
• Evidence of nodal disease greater than or equal to 15 mm in short axis as these findings are concerning for metastases that would not be targeted with radium-223 alone (Arm B). However, lymph nodes with short axis measurements between 1.5-3cm that have not enlarged more than 5mm (to account for reader variability) over the last 6 months and which are not inducing symptoms, causing obstruction, or in the opinion of the investigator pose a risk of impending obstruction of any structures, will be allowed.
• Pulmonary nodules \>10 mm
• Pulmonary nodules \>10mm that have been stable for \>6 months and are not clearly metastatic disease per the treating investigator are permitted
• Soft tissue components of bone metastases ≥ 1.0 cm in longest axis
• Soft tissue components of bone metastases \< 1.0 cm that have been stable for \>6 months (must not have enlarged \> 5mm) are permitted
• Soft tissue lesions ≥ 1.0 cm in longest axis
• Soft tissue lesions \< 1.0 cm that have been stable for \> 6 months (must not have enlarged \> 5mm) are permitted.
• If present, primary disease in the prostate must be stable for \> 6 months (defined as no growth \> 5mm)
• Evidence of local recurrence in the prostate bed
• Evidence of liver metastases or visceral disease
• Has a diagnosis of immunodeficiency
• Receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Patients who have received acute, low-dose, systemic immunosuppressant medications (e.g., limited low-dose dexamethasone for nausea, multiple doses for contrast allergy) may be enrolled in the study and would not require a 7 day washout.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (2)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Radium-223; radium Ra 223 dichloride; pembrolizumab

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: Atish Choudhury
• Organization: Dana Farber Cancer Institute

achoudhury@partners.org

617-632-6328

Study Officials

• Atish Choudhury, MD

  Dana-Farber Cancer Institute

  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: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 15, 2017
• First Posted: March 28, 2017
• Study Start: June 9, 2017
• Primary Completion: April 9, 2020
• Study Completion: February 28, 2025
• Last Updated: March 28, 2025
• Results First Posted: July 20, 2022

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)