Study NCT04237584
A Study Comparing ARB With Radium-223 vs ARB Therapy With Placebo and the Effect Upon Survival for mCRPC Patients (ESCALATE)
Submitted Date:  May 23, 2022 (v8)
Quality Control Review Has Not Concluded

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Open or close this module Study Identification
Unique Protocol ID: PC18-1005
Brief Title: A Study Comparing ARB With Radium-223 vs ARB Therapy With Placebo and the Effect Upon Survival for mCRPC Patients (ESCALATE)
Official Title: ESCALATE, A Phase III Randomized Study Comparing Enzalutamide or Darolutamide With Radium-223 vs Enzalutamide or Darolutamide With Placebo and the Effect Upon Symptomatic Skeletal Event-Free Survival for mCRPC Patients
Secondary IDs:
Open or close this module Study Status
Record Verification: May 2022
Overall Status: Terminated [The study was stopped due to insurmountable enrollment challenges affecting trial accrual, resulting from the rapidly evolving treatment options for advanced prostate cancer.]
Study Start: June 30, 2020
Primary Completion: March 7, 2022 [Actual]
Study Completion: March 7, 2022 [Actual]
First Submitted: January 15, 2020
First Submitted that
Met QC Criteria:
January 21, 2020
First Posted: January 23, 2020 [Actual]
Last Update Submitted that
Met QC Criteria:
Last Update Posted: June 21, 2022 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: MANA RBM
Responsible Party: Sponsor
Collaborators: Bayer
Carolina Urologic Research Center
Tulane University
Barbara Ann Karmanos Cancer Institute
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: No
Open or close this module Study Description
Brief Summary: This is a randomized, multi-center, double-blind, Phase III study of radium-223 plus enzalutamide or darolutamide compared to enzalutamide or darolutamide treatment plus placebo.
Detailed Description: The hypothesis investigators will test in this study is whether layering radium-223 following 16 weeks of enzalutamide or darolutamide exposure in patients demonstrating a biochemical response improves disease outcomes. By adding radium-223 following a potential bone flare phenomenon [after first 12-14 weeks of therapy with an androgen receptor blocker (ARB)], including patients expected to have durable response to systemic therapy, and mandating the use of bone protective agents during treatment, the investigators aim to demonstrate an optimal time to add radium-223 in the mCRPC landscape.
Open or close this module Conditions
Conditions: Metastatic Castration-resistant Prostate Cancer
Keywords: mCRPC
ARB
Radiopharmaceutical
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 3
Interventional Study Model: Sequential Assignment
Lead-in open-label androgen-receptor blocker (ARB) followed by double-blind Radium-223 or placebo.
Number of Arms: 2
Masking: Double (Participant, Investigator)
Allocation: Randomized
Enrollment: 23 [Actual]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Active Comparator: Lead-in ARB followed by Radium-223/ARB
Randomized, Open-label Lead-in ARB (Enzalutamide or Darolutamide) followed by Radium-223 + ARB.
Drug: Darolutamide
Participants will be randomly assigned to 12 weeks lead-in ARB (darolutamide or enzalutamide) that will continue after double-blind randomization to radium-223 or placebo.
Other Names:
  • Nubeqa
Drug: Enzalutamide
Participants will be randomly assigned to 12 weeks lead-in ARB (darolutamide or enzalutamide) that will continue after double-blind randomization to radium-223 or placebo.
Other Names:
  • Xtandi
Drug: Radium-223
After a 12-week lead-in period of open-label ARB, participants will be randomized to double-blind radium-223 or placebo. Participants will continue on their randomized, open-label ARB.
Other Names:
  • Xofigo
Placebo Comparator: Lead-in ARB followed by Placebo/ARB
Randomized, Open-label Lead-in ARB (Enzalutamide or Darolutamide) followed by Placebo + ARB.
Drug: Darolutamide
Participants will be randomly assigned to 12 weeks lead-in ARB (darolutamide or enzalutamide) that will continue after double-blind randomization to radium-223 or placebo.
Other Names:
  • Nubeqa
Drug: Enzalutamide
Participants will be randomly assigned to 12 weeks lead-in ARB (darolutamide or enzalutamide) that will continue after double-blind randomization to radium-223 or placebo.
Other Names:
  • Xtandi
Placebo
After a 12-week lead-in period of open-label ARB, participants will be randomized to double-blind radium-223 or placebo. Participants will continue on their randomized, open-label ARB.
Other Names:
  • Saline solution
Open or close this module Outcome Measures
[See Results Section.]
Primary Outcome Measures:
1. Symptomatic Skeletal Event-free Survival (SSE-FS)
[ Time Frame: through study completion, an average of 5 years ]

SSE-FS is a composite endpoint, composed of 4 events that indicate disease progression:

  • the first use of external-beam radiation therapy to relieve skeletal tumor-related symptoms
  • the occurrence of new symptomatic pathologic bone fractures.
  • the occurrence of new symptomatic spinal cord compression
  • a tumor-related orthopedic surgical intervention

Quality Control Review Comment provided by the National Library of Medicine:

  1. The Time Frame appears inconsistent with information provided here or in other parts of the record.
Secondary Outcome Measures:
1. Overall Survival (OS)
[ Time Frame: through study completion, an average of 5 years ]

2. Time to Chemotherapy Initiation
[ Time Frame: through study completion, an average of 5 years ]

3. Radiographic Progression-free Survival (rPFS)
[ Time Frame: through study completion, an average of 5 years ]

4. Safety Profile of Androgen Receptor Blocker (ARB) Therapy With or Without Radium-223; Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v5.0.
[ Time Frame: through study completion, an average of 5 years ]

5. Occurrence of AESI: Bone Fractures (Pathologic and Non-pathologic)
[ Time Frame: through study completion, an average of 5 years ]

Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: Male
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  1. Able and willing to provide informed consent.
  2. Histologically or cytologically confirmed diagnosis of prostate adenocarcinoma.
  3. Men ≥ 18 years.
  4. ECOG performance status of 0 or 1 at screening.
  5. Metastatic to bone with ≥ 2 bone metastases (area of increased uptake on 99mTc bone scan); equivocal lesions on the bone scan must be confirmed by standard X-ray, CT, or MRI.
  6. Patients must have progressive metastatic castration-resistant prostate cancer (mCRPC) at screening and on androgen deprivation therapy (ADT) as evidenced by either:
    1. For patients who manifest disease progression solely as a rising prostate-specific antigen (PSA) level - documentation of a sequence of two rising PSA values at a minimum of 1-week apart with the Screening value ≥1 ng/ml (see Appendix D);
    2. For patients with disease progression manifested in the bone, irrespective of progression by rising PSA - defined by the appearance of 2 or more new skeletal lesions demonstrated by 99Tc bone imaging. Ambiguous results should be confirmed by other imaging modalities than bone scan and x-ray (e.g.: CT-scan or MRI).
    3. For patients with disease progression manifested at nodal sites, irrespective of progression by rising PSA - progression defined per RECIST 1.1.
  7. Ongoing ADT with luteinizing hormone-releasing hormone (LHRH) agonist or antagonist or bilateral orchiectomy.
  8. Use of bone health agents (denosumab or zoledronic acid or other bisphosphonates) starting any time prior to R1 unless contraindicated or considered not in the best interest of the patient. A waiver must be approved by the medical monitor if bone health agents cannot be used. Bone health agents should be continued throughout both RT1 and RT2 treatment periods.
  9. Adequate bone marrow and organ function as defined by:
    1. Hemoglobin ≥ 10.0 g/dL
    2. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
    3. Platelets ≥ 100 x 109/L
    4. Serum creatinine ≤ 1.95 mg/dL
    5. Estimated creatinine clearance >/= 30 mL/min by Cockroft-Gault calculation
    6. Alanine aminotransferase (ALT) ≤ 175 U/L
    7. Aspartate aminotransferase (AST) ≤ 100 U/L
    8. Total bilirubin ≤ 1.8 mg/dL (unless the patient a diagnosis of Gilbert's disease or a similar syndrome involving slow conjugation of bilirubin; in patients with Gilbert's, the total bilirubin should be less than 6 mg/dL if patient has Gilbert's and the elevation should be seen in the unconjugated or indirect bilirubin measurement)
    9. LDH ≤ 224 U/L at screening.
    10. Albumin ≥ 2.5 g/dL
  10. Fertile male patients, defined as all males physiologically capable of conceiving offspring with female partners of child-bearing potential, must be willing to use condoms plus spermicidal agent during the study treatment period and for 6 months after the last dose of study drug, and not father a child or donate sperm during this period.
  11. The treating site investigator deems RT1 (Enzalutamide or Darolutamide) treatment safe and feasible.

    Subjects must meet the remaining inclusion criteria in order to be qualified for the second randomization (R2). Only subjects that complete the initial 12 weeks of run-in RT1 should be evaluated. Prior inclusion criteria do not need to be re-evaluated:

  12. Patients must have a documented ≥ 30% decline of PSA at any time during the 12 weeks of RT1.
  13. Patients must have no evidence of visceral metastatic disease at the time of RT2 randomization
  14. Ongoing treatment with RT1 and bone health agents at time of RT2 randomization.
  15. The treating site investigator deems RT2 (Ra-223 dichloride) treatment safe and feasible.

Exclusion Criteria:

  1. Pathological finding consistent with small cell carcinoma of the prostate.
  2. Prior chemotherapy for CRPC. Prior docetaxel for hormone-sensitive disease is permitted under the following conditions: started within 3 months of ADT initiation, given for a maximum of 6 cycles and progression occurred > 6 months after the last dose of docetaxel.
  3. Prior treatment for mCRPC or CRPC. However, the following therapies are permitted and not exclusionary: Sipuleucel-T, 5-alpha-reductase inhibitors, estrogens, or older antiandrogens (such as flutamide, bicalutamide, or nilutamide).
  4. Prior treatment for more than 2 months with CYP17 inhibitors (e.g. abiraterone or orteronel).
  5. Prior treatment for more than 2 months with agents inhibiting androgen receptor signaling (e.g. enzalutamide, apalutamide, or darolutamide).
  6. Prior hemibody or whole-body external radiotherapy. Other types of prior external radiotherapy and brachytherapies are allowed.
  7. Prior therapy with radionuclides (e.g., radium-223, strontium-89, samarium-153, rhenium-186, rhenium-188, actinium-225 and lutetium-177).
  8. Current involvement in any drug or device trial involving investigational agent or medical device within the last 28 days prior to R1.
  9. In general, any prior investigational agent for nmCRPC/mCRPC; however, may be reviewed by medical monitor/PIs for waiver consideration, on a case-by-case basis.
  10. Hypersensitivity to compounds related to enzalutamide, darolutamide, or Ra-223.
  11. A blood transfusion ≤ 28 days prior to R1.
  12. Major surgical procedures ≤ 28 days or minor surgical procedures ≤7 days prior to R1. No waiting period is required following port-a-cath placement.
  13. Patients with visceral metastases, clinical evidence of central nervous system metastases, or leptomeningeal tumor spread as demonstrated via CT/MRI of chest, abdomen, pelvis, and CNS (if needed). CT/MRI of the CNS only performed if suspicion of CNS metastases or leptomeningeal tumor spread. Nodules < 1 cm alone will not be considered visceral metastases. Renal masses < 3 cm will not be considered exclusionary.
  14. Serious active infection at the time of screening or another serious underlying medical condition that would impair the ability of the patient to receive protocol treatment.
  15. Presence of other active cancers, or history of treatment for invasive cancer ≤2 years of R1. Patients with Stage I/II cancer who have received definitive local treatment and are considered unlikely to recur are eligible. All patients with previously treated in situ carcinoma (i.e., non-invasive) and superficial bladder cancer are eligible, as are patients with history of non-melanoma skin cancer.
  16. Any other serious or unstable illness, or medical, social, or psychological condition, that could jeopardize the safety of the subject and/or his/her compliance with study procedures, or may interfere with the subject's participation in the study or evaluation of the study results."
Open or close this module Contacts/Locations
Study Officials: Neal Shore, MD
Study Chair
Carolina Urologic Research Center
Locations: United States, South Carolina
Research Site
Myrtle Beach, South Carolina, United States, 29572
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Citations:
Links:
Available IPD/Information:
Open or close this module Document Section
Study Protocol
Document Date: May 4, 2020
Uploaded: 05/23/2022 15:38
File Name: Prot_000.pdf
Informed Consent Form
Document Date: April 1, 2020
Uploaded: 05/23/2022 15:39
File Name: ICF_001.pdf
No Statistical Analysis Plan (SAP) exists for this study.

Quality Control Review Comment provided by the National Library of Medicine:

  1. The Document Type or Document Date appear inconsistent with information in an uploaded study document.
Study Results
Open or close this module Participant Flow
Recruitment Details Recruitment occurred from Jun 2020- Jul 2021 at selected medical centers that specialized in the treatment of advanced prostate cancer.
Pre-assignment Details 2/23 (8.7%) subjects did not meet all entry criteria (screen failed). 21/23 (91.3%) subjects met all entry criteria and were randomized to ARB. For the lead-in ARB period, 10 subjects were assigned to darolutamide and 11 were assigned to enzalutamide. Of these, 3 subjects on darolutamide discontinued early (1 due to adverse event and 2 did not meet R2 entry criteria) and 2 subjects on enzalutamide discontinued early (1 due to adverse event and 1 did not meet R2 entry criteria).
 
Arm/Group Title Lead-in ARB Followed by Radium-223/ARB Lead-in ARB Followed by Placebo/ARB
Arm/Group Description

Randomized, Open-label Lead-in ARB (Enzalutamide or Darolutamide) followed by Radium-223 + ARB.

Darolutamide: Participants will be randomly assigned to 12 weeks lead-in ARB (darolutamide or enzalutamide) that will continue after double-blind randomization to radium-223 or placebo.

Enzalutamide: Participants will be randomly assigned to 12 weeks lead-in ARB (darolutamide or enzalutamide) that will continue after double-blind randomization to radium-223 or placebo.

Radium-223: After a 12-week lead-in period of open-label ARB, participants will be randomized to double-blind radium-223 or placebo. Participants will continue on their randomized, open-label ARB.

Randomized, Open-label Lead-in ARB (Enzalutamide or Darolutamide) followed by Placebo + ARB.

Darolutamide: Participants will be randomly assigned to 12 weeks lead-in ARB (darolutamide or enzalutamide) that will continue after double-blind randomization to radium-223 or placebo.

Enzalutamide: Participants will be randomly assigned to 12 weeks lead-in ARB (darolutamide or enzalutamide) that will continue after double-blind randomization to radium-223 or placebo.

Placebo: After a 12-week lead-in period of open-label ARB, participants will be randomized to double-blind radium-223 or placebo. Participants will continue on their randomized, open-label ARB.

Period Title: Overall Study
Started 8 8
Completed 0 0
Not Completed 8 8
Reason Not Completed
Physician Decision 0 1
Sponsor Decision 8 7

Quality Control Review Comment provided by the National Library of Medicine:

  1. The participant flow appears to include insufficient information to understand the arms/groups to which participants were assigned, the intervention strategy used in each arm/group, or how participants progressed in the study.
Open or close this module Baseline Characteristics

Quality Control Review Comment provided by the National Library of Medicine:

  1. The arms/groups appear inconsistent with information in other parts of the record. Each arm/group should be described separately, or a valid explanation provided.
Arm/Group TitleLead-in ARB Followed by Radium-223/ARBLead-in ARB Followed by Placebo/ARBTotal
Arm/Group Description

Randomized, Open-label Lead-in ARB (Enzalutamide or Darolutamide) followed by Radium-223 + ARB.

Darolutamide: Participants will be randomly assigned to 12 weeks lead-in ARB (darolutamide or enzalutamide) that will continue after double-blind randomization to radium-223 or placebo.

Enzalutamide: Participants will be randomly assigned to 12 weeks lead-in ARB (darolutamide or enzalutamide) that will continue after double-blind randomization to radium-223 or placebo.

Radium-223: After a 12-week lead-in period of open-label ARB, participants will be randomized to double-blind radium-223 or placebo. Participants will continue on their randomized, open-label ARB.

Randomized, Open-label Lead-in ARB (Enzalutamide or Darolutamide) followed by Placebo + ARB.

Darolutamide: Participants will be randomly assigned to 12 weeks lead-in ARB (darolutamide or enzalutamide) that will continue after double-blind randomization to radium-223 or placebo.

Enzalutamide: Participants will be randomly assigned to 12 weeks lead-in ARB (darolutamide or enzalutamide) that will continue after double-blind randomization to radium-223 or placebo.

Placebo: After a 12-week lead-in period of open-label ARB, participants will be randomized to double-blind radium-223 or placebo. Participants will continue on their randomized, open-label ARB.

Total of all reporting groups
Overall Number of Baseline Participants 8 8 16
Baseline Analysis Population Description [Not Specified]
Age, Categorical
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed8 Participants8 Participants16 Participants
<=18 years
0
0%
0
0%
0
0%
Between 18 and 65 years
0
0%
1
12.5%
1
6.25%
>=65 years
8
100%
7
87.5%
15
93.75%
Sex/Gender, Customized
Measure Type: Number
Unit of measure: males only - prostate cancer
Number Analyzed8 Participants8 Participants16 Participants
Males with prostate cancer
8816

Quality Control Review Comment provided by the National Library of Medicine:

  1. The Unit of Measure appears invalid.
Ethnicity (NIH/OMB)
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed8 Participants8 Participants16 Participants
Hispanic or Latino
1
12.5%
1
12.5%
2
12.5%
Not Hispanic or Latino
7
87.5%
7
87.5%
14
87.5%
Unknown or Not Reported
0
0%
0
0%
0
0%
Race (NIH/OMB)
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed8 Participants8 Participants16 Participants
American Indian or Alaska Native
0
0%
0
0%
0
0%
Asian
0
0%
0
0%
0
0%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
0
0%
Black or African American
1
12.5%
1
12.5%
2
12.5%
White
7
87.5%
7
87.5%
14
87.5%
More than one race
0
0%
0
0%
0
0%
Unknown or Not Reported
0
0%
0
0%
0
0%
Region of Enrollment
Measure Type: Number
Unit of measure: participants
Number Analyzed8 Participants8 Participants16 Participants
United States
8816
Concomitant use of bone health agents (osteoclast inhibitors)
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed8 Participants8 Participants16 Participants
8816
Open or close this module Outcome Measures
1. Primary Outcome:
Title Symptomatic Skeletal Event-free Survival (SSE-FS)
Description

SSE-FS is a composite endpoint, composed of 4 events that indicate disease progression:

  • the first use of external-beam radiation therapy to relieve skeletal tumor-related symptoms
  • the occurrence of new symptomatic pathologic bone fractures.
  • the occurrence of new symptomatic spinal cord compression
  • a tumor-related orthopedic surgical intervention
Time Frame through study completion, an average of 5 years

Quality Control Review Comment provided by the National Library of Medicine:

  1. The Time Frame appears inconsistent with information provided here or in other parts of the record.
Outcome Measure Data
Analysis Population Description
ESCALATE (PC18-1005) was terminated early due to enrollment challenges caused by rapidly evolving treatment options for mCRPC. The number of subjects enrolled were not sufficient for formal statistical analysis.
 
Arm/Group TitleLead-in ARB Followed by Radium-223/ARBLead-in ARB Followed by Placebo/ARB
Arm/Group Description

Randomized, Open-label Lead-in ARB (Enzalutamide or Darolutamide) followed by Radium-223 + ARB.

Darolutamide: Participants will be randomly assigned to 12 weeks lead-in ARB (darolutamide or enzalutamide) that will continue after double-blind randomization to radium-223 or placebo.

Enzalutamide: Participants will be randomly assigned to 12 weeks lead-in ARB (darolutamide or enzalutamide) that will continue after double-blind randomization to radium-223 or placebo.

Radium-223: After a 12-week lead-in period of open-label ARB, participants will be randomized to double-blind radium-223 or placebo. Participants will continue on their randomized, open-label ARB.

Randomized, Open-label Lead-in ARB (Enzalutamide or Darolutamide) followed by Placebo + ARB.

Darolutamide: Participants will be randomly assigned to 12 weeks lead-in ARB (darolutamide or enzalutamide) that will continue after double-blind randomization to radium-223 or placebo.

Enzalutamide: Participants will be randomly assigned to 12 weeks lead-in ARB (darolutamide or enzalutamide) that will continue after double-blind randomization to radium-223 or placebo.

Placebo: After a 12-week lead-in period of open-label ARB, participants will be randomized to double-blind radium-223 or placebo. Participants will continue on their randomized, open-label ARB.

Overall Number of Participants Analyzed0 0
No data displayed because Outcome Measure has zero total participants analyzed.

Quality Control Review Comment provided by the National Library of Medicine:

  1. Required information appears to be missing.
2. Secondary Outcome:
Title Overall Survival (OS)
Description
Time Frame through study completion, an average of 5 years
Outcome Measure Data Not Reported
3. Secondary Outcome:
Title Time to Chemotherapy Initiation
Description
Time Frame through study completion, an average of 5 years
Outcome Measure Data Not Reported
4. Secondary Outcome:
Title Radiographic Progression-free Survival (rPFS)
Description
Time Frame through study completion, an average of 5 years
Outcome Measure Data Not Reported
5. Secondary Outcome:
Title Safety Profile of Androgen Receptor Blocker (ARB) Therapy With or Without Radium-223; Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v5.0.
Description
Time Frame through study completion, an average of 5 years
Outcome Measure Data Not Reported
6. Secondary Outcome:
Title Occurrence of AESI: Bone Fractures (Pathologic and Non-pathologic)
Description
Time Frame through study completion, an average of 5 years
Outcome Measure Data Not Reported
Open or close this module Adverse Events
 
Time Frame Adverse events were collected on all enrolled subjects. Adverse event collection started at the first subject enrollment in June 2020 and concluded March 2022 when the final subject was 30 days post-last dose of study medication.
Adverse Event Reporting Description [Not specified]

Quality Control Review Comment provided by the National Library of Medicine:

  1. There does not appear to be sufficient information to understand the Time Frame.
 
Arm/Group Title Lead-in ARB Followed by Radium-223/ARB Lead-in ARB Followed by Placebo/ARB
Arm/Group Description

Randomized, Open-label Lead-in ARB (Enzalutamide or Darolutamide) followed by Radium-223 + ARB.

Darolutamide: Participants will be randomly assigned to 12 weeks lead-in ARB (darolutamide or enzalutamide) that will continue after double-blind randomization to radium-223 or placebo.

Enzalutamide: Participants will be randomly assigned to 12 weeks lead-in ARB (darolutamide or enzalutamide) that will continue after double-blind randomization to radium-223 or placebo.

Radium-223: After a 12-week lead-in period of open-label ARB, participants will be randomized to double-blind radium-223 or placebo. Participants will continue on their randomized, open-label ARB.

Randomized, Open-label Lead-in ARB (Enzalutamide or Darolutamide) followed by Placebo + ARB.

Darolutamide: Participants will be randomly assigned to 12 weeks lead-in ARB (darolutamide or enzalutamide) that will continue after double-blind randomization to radium-223 or placebo.

Enzalutamide: Participants will be randomly assigned to 12 weeks lead-in ARB (darolutamide or enzalutamide) that will continue after double-blind randomization to radium-223 or placebo.

Placebo: After a 12-week lead-in period of open-label ARB, participants will be randomized to double-blind radium-223 or placebo. Participants will continue on their randomized, open-label ARB.

Quality Control Review Comment provided by the National Library of Medicine:

  1. The arms/groups appear inconsistent with information in other parts of the record. Each arm/group should be described separately, or a valid explanation provided.
All-Cause Mortality
  Lead-in ARB Followed by Radium-223/ARBLead-in ARB Followed by Placebo/ARB
 Affected / At Risk (%)# Events Affected / At Risk (%)# Events
Total 0 / 8 (0%)0 / 8 (0%)
Serious Adverse Events
  Lead-in ARB Followed by Radium-223/ARBLead-in ARB Followed by Placebo/ARB
 Affected / At Risk (%)# Events Affected / At Risk (%)# Events
Total 1 / 8 (12.5%)1 / 8 (12.5%)
Infections and infestations
Pneumonia 0 / 8 (0%)01 / 8 (12.5%)1
Respiratory, thoracic and mediastinal disorders
Hypoxia 0 / 8 (0%)01 / 8 (12.5%)1
Vascular disorders
Hypotension 0 / 8 (0%)01 / 8 (12.5%)1
Syncope 1 / 8 (12.5%)10 / 8 (0%)0
Indicates events were collected by systematic assessment.
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
  Lead-in ARB Followed by Radium-223/ARBLead-in ARB Followed by Placebo/ARB
 Affected / At Risk (%)# Events Affected / At Risk (%)# Events
Total 8 / 8 (100%)8 / 8 (100%)
Cardiac disorders
Atrial fibrillation 1 / 8 (12.5%)10 / 8 (0%)0
Eye disorders
Cataract 1 / 8 (12.5%)20 / 8 (0%)0
Uveitis 1 / 8 (12.5%)10 / 8 (0%)0
Gastrointestinal disorders
Constipation 1 / 8 (12.5%)11 / 8 (12.5%)1
Diarrhoea 3 / 8 (37.5%)31 / 8 (12.5%)1
Nausea 2 / 8 (25%)20 / 8 (0%)0
Vomiting 1 / 8 (12.5%)10 / 8 (0%)0
General disorders
Decreased appetite 1 / 8 (12.5%)10 / 8 (0%)0
Fatigue 3 / 8 (37.5%)31 / 8 (12.5%)1
Gait disturbance 1 / 8 (12.5%)10 / 8 (0%)0
Infections and infestations
Corona virus infection 1 / 8 (12.5%)10 / 8 (0%)0
Injury, poisoning and procedural complications
Fall 0 / 8 (0%)01 / 8 (12.5%)1
Investigations
Neutrophil count decreased 1 / 8 (12.5%)10 / 8 (0%)0
White blood cell count decreased 1 / 8 (12.5%)10 / 8 (0%)0
Metabolism and nutrition disorders
Diabetic complication 1 / 8 (12.5%)10 / 8 (0%)0
Hypokalaemia 0 / 8 (0%)01 / 8 (12.5%)3
Musculoskeletal and connective tissue disorders
Arthralgia 1 / 8 (12.5%)12 / 8 (25%)2
Back Pain 0 / 8 (0%)02 / 8 (25%)2
Flank pain 1 / 8 (12.5%)10 / 8 (0%)0
Muscle spasms 0 / 8 (0%)01 / 8 (12.5%)1
Musculoskeletal chest pain 0 / 8 (0%)02 / 8 (25%)2
Myalgia 0 / 8 (0%)01 / 8 (12.5%)1
Pain in extremity 0 / 8 (0%)01 / 8 (12.5%)1
Pain in jaw 1 / 8 (12.5%)10 / 8 (0%)0
Rib fracture 1 / 8 (12.5%)10 / 8 (0%)0
Spinal pain 0 / 8 (0%)01 / 8 (12.5%)1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer Pain 0 / 8 (0%)01 / 8 (12.5%)1
Nervous system disorders
Confusional state 0 / 8 (0%)01 / 8 (12.5%)1
Dizziness 1 / 8 (12.5%)11 / 8 (12.5%)1
Hypoaesthesia 0 / 8 (0%)02 / 8 (25%)3
Paraesthesia 0 / 8 (0%)01 / 8 (12.5%)1
Peripheral sensory neuropathy 0 / 8 (0%)01 / 8 (12.5%)1
Restless legs syndrome 0 / 8 (0%)01 / 8 (12.5%)1
Taste disorder 1 / 8 (12.5%)10 / 8 (0%)0
Psychiatric disorders
Insomnia 0 / 8 (0%)01 / 8 (12.5%)1
Renal and urinary disorders
Dysuria 0 / 8 (0%)01 / 8 (12.5%)1
Pollakiuria 0 / 8 (0%)01 / 8 (12.5%)1
Reproductive system and breast disorders
Hot flush 1 / 8 (12.5%)10 / 8 (0%)0
Prostatic disorder 1 / 8 (12.5%)10 / 8 (0%)0
Respiratory, thoracic and mediastinal disorders
Dyspnoea 1 / 8 (12.5%)10 / 8 (0%)0
Nasopharyngitis 1 / 8 (12.5%)10 / 8 (0%)0
Oropharyngeal pain 1 / 8 (12.5%)10 / 8 (0%)0
Respiratory syncytial virus infection 0 / 8 (0%)01 / 8 (12.5%)1
Vascular disorders
Hot flush 1 / 8 (12.5%)10 / 8 (0%)0
Hypertension 1 / 8 (12.5%)10 / 8 (0%)0
Indicates events were collected by systematic assessment.
Open or close this module Limitations and Caveats
ESCALATE (PC18-1005) was terminated early due to enrollment challenges. Two subjects discontinued treatment and study due to adverse events while on lead-in ARB prior to the second randomization for Radium-223 or Placebo cycles. No subject discontinued due to adverse event after the second randomization. There were no deaths on study, and there were no SAEs attributable to study treatments. Vital signs, ECGs and laboratory studies were all within parameters typical for this population.

Quality Control Review Comment provided by the National Library of Medicine:

  1. A free-text field appears to include results data or conclusions drawn from the data. All results data must be reported in a tabular format.
Open or close this module More Information
Certain Agreements:
Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between the Principal Investigator and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact:
Name/Official Title:
Penelope Manasco, CEO
Organization:
MANA RBM
Phone:
9195566456
Email:
pmanasco@manarbm.com

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