Radium Ra 223 With Enzalutamide Compared to Enzalutamide Alone in Men With Metastatic Castration Refractory Prostate Cancer

NCT02199197 | Completed Phase 2 Results DMC

• 1 other identifier: HCI68770
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

Brief Summary

Study of Radium Ra 223 dichloride with enzalutamide compared to enzalutamide alone in men with metastatic castration refractory prostate cancer

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (2)

• Fold Change in Serum N-telopeptides From Baseline

  Patients had serum N-telopeptide labs drawn prior to the start of treatment and at the End of Treatment visit or at disease progression, whichever occurred first. The mean and standard deviation of the differences were calculated on a log 2 scale. Fold changes (post/pre) and 95% confidence intervals are reported.

  From prior to start of treatment to end of treatment or disease progression (approximately 6 months)

• Number of Participants With Adverse Events

  Adverse Events were assessed from start of Radium Ra 223 Dichloride or Enzalutamide treatment (whichever was started first) through 30 days after the last dose of either drug or until start of a new anti-cancer therapy, whichever came first. Adverse events were assessed using the Common Terminology for Adverse Events (CTCAE) version 4.0. Each event was assigned a grade (1-5), with lower grades indicating milder events. All adverse events were recorded, regardless of attribution to study treatment. Reported below are the number of patients who experienced any grade 3-5 non-hematological AE. A full listing of AEs affecting 5% or more participants are listed in the Adverse Events module of the Results section.

  From first dose of study treatment to 30 days following last dose (approximately 7 months)

Secondary Outcomes (6)

• Prostate Specific Antigen (PSA) Progression Free Survival (PFS)

  Up to 2 years (24 months)

• Radiographic Progression Free Survival (PFS)

  Up to 2 years (24 months)

• Bone Alkaline Phosphatase (ALP) Progression Free Survival (PFS)

  Up to 2 years (24 months)

• Count of Prostate Specific Antigen (PSA) Responses

  Up to 2 years after start of study treatment

• Count of Radiographic Responses

  Up to 2 years after start of study treatment

Study Arms (2)

Radium Ra 223 Dichloride and Enzalutamide

EXPERIMENTAL

Radium Ra 223 Dichloride and Enzalutamide administered concurrently for 6 28-day cycles.

Drug: Radium Ra 223 Dichloride; Drug: Enzalutamide

Enzalutamide alone

ACTIVE COMPARATOR

Enzalutamide administered as a single agent for 6 28-day cycles.

Drug: Enzalutamide

Interventions

Radium Ra 223 Dichloride DRUG

Radium Ra 223 Dichloride, 55 kilobecquerel (kBq)/kg body weight, administered as a bolus intravenous (IV) injection (up to 1 minute) on Day 1 of each cycle for 6 cycles.

Also known as: Xofigo, Alpharadin

Radium Ra 223 Dichloride and Enzalutamide

Enzalutamide DRUG

Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.

Also known as: Xtandi

Enzalutamide alone; Radium Ra 223 Dichloride and Enzalutamide

Eligibility Criteria

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

You may qualify if:

• Histologically documented adenocarcinoma of the prostate.
• Men at least 18 years of age and life expectancy of greater than or equal to 6 months.
• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.
• Metastatic disease as evidenced by both lymphadenopathy and bony metastases or just bony metastases on baseline bone scan and/or computed tomography (CT) scan or MRI of the abdomen and pelvis within 28 days of registration. Chest imaging is only required if clinically indicated or if there is known disease in the chest.
• Castration resistant prostatic adenocarcinoma. Subjects must have castrate levels of serum testosterone (less than 50 ng/dL) achieved by orchiectomy or luteinizing hormone-releasing hormone (LHRH) agonist or antagonist therapy.
• Previously received docetaxel or are not healthy enough per clinical judgment or declined to receive it
• Evidence of disease progression on or after the most recent systemic treatment defined by the following criteria:
• Prostate-Specific Antigen (PSA): Increasing serum PSA levels as defined by the Prostate Cancer Working Group 2 (PCWG2), determined by 2 consecutive measurements (compared to a baseline or nadir value). If the third measurement is below the second, then a fourth measurement must be greater than the second. The confirming third or fourth measurement must be greater or equal to 2 ng/mL. PSA progression must have occurred within 15 months of registration (with at least 7 days between each PSA measurement). Additionally, the PSA progression as described above should have occurred during or after the most recent systemic treatment for prostate cancer.
• Measurable disease: greater than or equal to 20% increase in the sum of the short axis diameter of all measurable lymph nodes or the development of any new measurable lymphadenopathy by RECIST 1.1 and PCWG2 criteria.
• Non-measurable disease:
• Lymph node disease: The appearance of 1 or more new lymphadenopathy, and/or unequivocal worsening of non-measurable disease when compared to imaging studies acquired during castration therapy or against the pre-castration studies if there was no response.
• Bone disease: Appearance of 2 or more new areas of abnormal uptake on bone scan when compared to imaging studies acquired during castration therapy or against the pre-castration studies if there was no response. Increased uptake of pre-existing lesions on bone scan does not constitute progression.
• Symptomatic bone metastases
• Adequate hematologic, renal, and liver function as evidenced by laboratory test results. (Transfusion of blood products are not allowed to normalize blood parameters within 4 weeks of the first radium treatment.)
• Subjects who have previously received docetaxel or are ineligible for docetaxel and who are candidates for treatment with enzalutamide alone or enzalutamide in combination with Radium-223

You may not qualify if:

• The presence of known brain metastases, malignant pleural effusions, or malignant ascites. Brain MRI is required at screening only if clinically indicated.
• Visceral metastases as assessed by chest, abdominal or pelvic computed tomography (CT) (or other imaging modality)
• Received systemic therapy with radionuclides (e.g., strontium-89, samarium-153, rhenium-186, or rhenium-188, or Radium Ra 223 dichloride) for the treatment of bony metastases
• Prior treatment with enzalutamide.
• Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, or tumor embolization) other than the protocol based treatment. LHRH agonist or antagonist therapy, and supportive non-cancer directed therapies like bisphosphonates or denosumab are allowed.
• Prior cytoxic chemotherapy with the exception of docetaxel or cabazitaxel. Treatment with docetaxel or cabazitaxel must be discontinued greater than 4 weeks from the time of enrollment, and recovery of adverse events (AEs) to grade 1 or baseline (however, ongoing neuropathy is permitted).
• Major surgery within 30 days prior to start of study drug
• Current, untreated pathologic long-bone fractures, imminent pathologic long-bone fractures (cortical erosion on radiography greater than 50%).
• Prior hemi-body external radiotherapy. Subjects who received other types of prior external radiotherapy are allowed provided that bone marrow function is assessed and meets the protocol requirements for hemoglobin, absolute neutrophil count (ANC), and platelets.
• Use of biologic response modifiers, such as granulocyte macrophage colony-stimulating factor (GM-CSF) or granulocyte colony-stimulating factor (G-CSF) within 4 weeks prior to screening
• Lymphadenopathy exceeding 3 cm in short-axis diameter
• Any size pelvic lymphadenopathy if it is thought to be a contributor to concurrent hydronephrosis.
• Current or imminent spinal cord compression based on clinical findings and/or magnetic resonance imaging (MRI). Treatment should be completed for spinal cord compression.
• Any other serious illness or medical condition in the opinion of the investigator, such as but not limited to:
• Any greater than or equal to Grade 2 infection as defined by NCI-CTCAE version 4.03.

Sponsors & Collaborators

• University of Utah: lead

Study Sites (1)

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Related Publications (1)

• Agarwal N, Nussenzveig R, Hahn AW, Hoffman JM, Morton K, Gupta S, Batten J, Thorley J, Hawks J, Santos VS, Nachaegari G, Wang X, Boucher K, Haaland B, Maughan BL. Prospective Evaluation of Bone Metabolic Markers as Surrogate Markers of Response to Radium-223 Therapy in Metastatic Castration-resistant Prostate Cancer. Clin Cancer Res. 2020 May 1;26(9):2104-2110. doi: 10.1158/1078-0432.CCR-19-2591. Epub 2020 Jan 14.

  PMID: 31937614 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

radium Ra 223 dichloride; enzalutamide

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: Data Manager
• Organization: Huntsman Cancer Institute Research Compliance Office

compliance@hci.utah.edu

801-585-0601

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: April 22, 2014
• First Posted: July 24, 2014
• Study Start: June 25, 2014
• Primary Completion: April 19, 2018
• Study Completion: October 3, 2019
• Last Updated: October 30, 2020
• Results First Posted: May 21, 2019

Record last verified: 2020-10

Locations

US (1)