Prostate CancerNCT03677076
Clonal Emergence and Regression During Radium-223 Therapy for Metastatic Prostate Cancer
An observational study of Prostate Cancer, run by Medical University of South Carolina at 1 site in United States.
Trial summary
This study is for patients with metastatic prostate cancer receiving radium-223 as their standard of care therapy. The researchers will collect blood and urine samples from patients before, during and after the radium-223 therapy. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- Ancillary/Correlative
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Mar 2019to 31 Dec 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Study population: adult males with prostate cancer receiving radium223 treatment
Who may be able to join
- Prostate adenocarcinoma by history or medical records.
- Two or more bone metastases as demonstrated by imaging studies (technetium bone scan, fluoride PET scan, FDG PET scan, fluciclovine PET scan, CT scan, or MRI scan) or by biopsy.
- Patients must be on ADT with a GnRH receptor agonist/antagonist or orchiectomy, with or without an anti-androgen or testosterone synthesis inhibitor. Patients must have a documented castrate level of testosterone (<50ng/dL) and be willing to continue their GnRH agonist/antagonist during the course of radium-223 therapy.
- Patients may have had localized external beam radiation to as much as 20% of the skeleton
- Adequate hematopoietic, renal, and hepatic function. These parameters include:
- Hemoglobin ≥ 10gm/dL
Show all 20Show fewer
- WBC ≥ 3.0K/mcL
- ANC ≥ 1.5K/mcL
- Platelet count ≥ 100K/mcL
- Creatinine < 1.5 ng/mL
- Total bilirubin <1.5 ng/mL.
- Albumin > 25 g/L
- Patients should have an elevated, relevant tumor marker such as PSA, CEA, or LDH.
- Age ≥18 years old
- Life expectancy of at least 24 weeks
- Subjects must be able to understand and be willing to sign the written informed consent form. A signed informed consent form must be appropriately obtained prior to the conduct of any trial-specific procedures. Subjects must be willing and able to comply with the protocol, including follow-up visits and examinations.
- Men of childbearing potential must agree to use adequate contraception beginning at the signing of the informed consent until at least 30 days after the last dose of radium-223 treatment or during the course of radium-223 treatment.
- Subjects must have had a Guardant 360 ctDNA-based genomic profile performed up to four months prior to the first dose of radium-223, with no new therapy started in the interim. This assay must show at least one single nucleotide variant, either missense or synonymous, or one amplification.
- Subjects should continue any previously-started bone-hardening agents (zoledronic acid or denosumab) during radium-223 therapy.
- All acute toxic effects of any prior treatment have resolved to NCI-CTCAE v 5.0 Grade 1 or less at the time of signing the Informed Consent Form (ICF).
Who cannot join
- Initiation of any additional anti-tumor therapy within 2 months of starting radium-223 treatment
- Presence of only lytic bone metastases
- Prior cytotoxic chemotherapy for metastatic PCa
- Prior 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
- Other malignancy requiring systemic therapy within the last 3 years (except non melanoma skin cancer or low-grade superficial bladder cancer)
- Visceral (i.e. liver, lung, brain, adrenal, brain, but not lymph node) metastases as assessed by chest, abdominal, or pelvic computed tomography, or other imaging modality)
Show all 16Show fewer
- Lymphadenopathy exceeding 6 cm in short-axis diameter, or any size pelvic lymphadenopathy if it is thought to be a contributor to concurrent hydronephrosis
- Imminent spinal cord compression based on clinical findings and/or MRI. Treatment should be completed for spinal cord compression.
- Any infection ≥ Grade 2 per NCI-CTCAE version 5.0
- Cardiac failure NYHA III or IV
- Crohn's disease or ulcerative colitis
- Bone marrow dysplasia, myelodysplasia
- Fecal incontinence
- Inability to comply with the protocol and/or not willing or not available for follow-up assessments.
- Any condition which, in the investigator's opinion, makes the subject unsuitable for trial participation.
- Concurrent use of abiraterone or enzalutamide. A 28-day washout period is required for both agents.
Trial locations and contacts
1 site in 1 country.
United States1 site
Medical University of South Carolina
Charleston, South Carolina, 29425
About this study
This study is for patients with metastatic prostate cancer receiving radium-223 as their standard of care therapy. The researchers will collect blood and urine samples from patients before, during and after the radium-223 therapy. The researchers will compare these samples to observe how the treatment has affected different cancer markers.
Read the detailed description
This study proposes to document the presence of clonal emergence and regression during radium-223 therapy for metastatic prostate cancer by serial ctDNA analysis of tumor-associated mutations, using the clinically-available Guardant 360 platform. These data may provide important mechanistic insights into radium-223 therapy by 1) identifying mutations associated with radium-223 resistance or sensitivity, 2) providing new markers of treatment response in an individual, and 3) revealing antitumor effects from radium-223 that are not easily recognized with standard tumor response metrics. Positive finding based on this clinically-available platform will be readily applied by the oncology treatment community.
- Conditions
- Prostate Cancer
- Being tested
- Ancillary/Correlative
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ancillary/CorrelativeOther
Collection of research blood and urine
| Study group | Role | What they receive |
|---|---|---|
| Ancillary/Correlative | Patients will complete questionnaires and have research blood drawn. Receives: Other: Ancillary/Correlative |
What is being measured
The primary outcome is the main question the study is designed to answer.
Minor allele frequency (MAF) in ctDNA
The primary objective is to estimate average change in MAF in one or more clonal SNVs, comparing baseline to on-treatment, and baseline to post-treatment samples
Measured: 24 months
Secondary outcomes (5)
Changes in MAF of clonal SNV
- Determine if changes from baseline in MAF of clonal SNVs during therapy and post-treatment differ significantly from 0.
Measured: 24 months
Change in clonal mutation MAF and change in pain
- Evaluate the association between change from baseline in clonal mutation MAF and change in pain (evaluated by VAS pain score and analgesic usage diary), measured both during therapy and post-treatment.
Measured: 24 months
Change in clonal mutation MAF and change in tumor markers
- Evaluate the association between change in clonal mutation MAF and change in tumor markers, including prostate specific antigen (PSA), CEA and LDH, measured by standard biochemical assays both during therapy and post-treatment.
Measured: 24 months
Change in clonal mutation MAF and markers of bone metabolism
- Evaluate the association between change in clonal mutation MAF and markers of bone metabolism including urine N-telopeptide and serum bone-specific alkaline phosphatase, measured by ELISA assays both during therapy and post-treatment.
Measured: 24 months
Change in clonal mutation MAF and presence of the TMPRSS2-ERG fusion gene
- Evaluate the association between change in clonal mutation MAF and presence of the TMPRSS2-ERG fusion gene, measured in plasma/urine by digital PCR Evaluate the association between change in clonal mutation MAF and clinical benefit, (time from the last dose of radium-223 to the initiation of a new systemic therapy, measured at least 60 days after final dose) and change in QOL (measured by FACT-P instrument).
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2018
- Study start4 Mar 2019
- Primary completion31 Dec 2023
- Study completion31 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by Medical University of South CarolinaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of South Carolina
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Michael Lilly, MD, Principal investigator, Medical University of South Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03677076
- Sponsor's protocol ID
- 102691
- Other IDs
- IIR-US-2017-4183
- Status last verified
- Jan 2024
- First submitted
- 18 Sep 2018
- Last updated
- 17 Jan 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clonal Emergence and Regression During Radium-223 Therapy for Metastatic Prostate Cancer
- ClinicalTrials.gov ID
- NCT03677076
- Acronym / sponsor ID
- 102691
- Conditions
- Prostate Cancer
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Medical University of South CarolinaUniversity, hospital or other
- Study start
- 4 Mar 2019 (actual)
- Primary completion
- 31 Dec 2023 (actual)
- Study completion
- 31 Dec 2023 (actual)
- First posted
- 19 Sep 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is for patients with metastatic prostate cancer receiving radium-223 as their standard of care therapy. The researchers will collect blood and urine samples from patients before, during and after the radium-223 therapy. The researchers will compare these samples to observe how the treatment has affected different cancer markers.
Detailed description
This study proposes to document the presence of clonal emergence and regression during radium-223 therapy for metastatic prostate cancer by serial ctDNA analysis of tumor-associated mutations, using the clinically-available Guardant 360 platform. These data may provide important mechanistic insights into radium-223 therapy by 1) identifying mutations associated with radium-223 resistance or sensitivity, 2) providing new markers of treatment response in an individual, and 3) revealing antitumor effects from radium-223 that are not easily recognized with standard tumor response metrics. Positive finding based on this clinically-available platform will be readily applied by the oncology treatment community.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ancillary/Correlative | – | Other: Ancillary/CorrelativePatients will complete questionnaires and have research blood drawn. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- adult males with prostate cancer receiving radium223 treatment
Key inclusion criteria (20 listed)
- Prostate adenocarcinoma by history or medical records.
- Two or more bone metastases as demonstrated by imaging studies (technetium bone scan, fluoride PET scan, FDG PET scan, fluciclovine PET scan, CT scan, or MRI scan) or by biopsy.
- Patients must be on ADT with a GnRH receptor agonist/antagonist or orchiectomy, with or without an anti-androgen or testosterone synthesis inhibitor. Patients must have a documented castrate level of testosterone (<50ng/dL) and be willing to continue their GnRH agonist/antagonist during the course of radium-223 therapy.
- Patients may have had localized external beam radiation to as much as 20% of the skeleton
- Adequate hematopoietic, renal, and hepatic function. These parameters include:
Key exclusion criteria (16 listed)
- Initiation of any additional anti-tumor therapy within 2 months of starting radium-223 treatment
- Presence of only lytic bone metastases
- Prior cytotoxic chemotherapy for metastatic PCa
- Prior 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
- Other malignancy requiring systemic therapy within the last 3 years (except non melanoma skin cancer or low-grade superficial bladder cancer)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ancillary/CorrelativeCollection of research blood and urine | Other | Ancillary/Correlative |
Primary outcome
Minor allele frequency (MAF) in ctDNA
Time frame: 24 months
The primary objective is to estimate average change in MAF in one or more clonal SNVs, comparing baseline to on-treatment, and baseline to post-treatment samples
5 secondary outcomes
Changes in MAF of clonal SNV
Time frame: 24 months
Change in clonal mutation MAF and change in pain
Time frame: 24 months
Change in clonal mutation MAF and change in tumor markers
Time frame: 24 months
Change in clonal mutation MAF and markers of bone metabolism
Time frame: 24 months
Change in clonal mutation MAF and presence of the TMPRSS2-ERG fusion gene
Time frame: 24 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jan 2024.
- Individual participant dataSharing planned: No
Related trials for Prostate Cancer
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
Active, not recruitingObservational study
MRI Fusion Biopsy vs. Micro-Ultrasound Guided Biopsy
Prostate Cancer
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
Not yet recruitingPhase 1/2
STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer
Recruiting
Rehabilitation and Sex Therapy to Optimize Recovery After Prostate Cancer Treatment
Prostate Cancer, Urinary Incontinence
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Lilly, MD principal investigator
Medical University of South Carolina
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Prostate Cancer, run by Medical University of South Carolina at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Minor allele frequency (MAF) in ctDNA (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jan 2024.