Prostate CancerPhase 2NCT02903160
Prostate Cancer Intensive, Non-Cross Reactive Therapy (PRINT) for Castration Resistant Prostate Cancer (CRPC)
A Phase 2 study testing Abiraterone acetate, Prednisone and Radium-223 dichloride in people with Prostate Cancer, run by Icahn School of Medicine at Mount Sinai at 2 sites in United States.
Trial summary
The purpose of this study is to determine the clinical benefits of using a rapidly cycling, non-cross reactive regimen of FDA-approved prostate cancer therapeutic agents in the management of castration resistant prostate cancer. 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?
- Abiraterone acetate, Prednisone and Radium-223 dichloride
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 2 sitesUnited States
- Study dates
- 13 Jan 2017to 15 Nov 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
Who may be able to join
- Histologically or cytologically confirmed adenocarcinoma of the prostate
- Metastatic castrate resistant prostate cancer, defined by progressive disease based on either rising PSA, new bone metastases, or progression of measurable disease on standard imaging, according to PCWG2 guidelines, despite androgen deprivation therapy
- Ongoing androgen deprivation therapy with a GnRH analogue, GnRH antagonist, or bilateral orchiectomy
- ECOG performance status 0-1
- Serum testosterone level < 50 ng/dL
- Absolute neutrophil count > 1,500/μL, platelet count > 100,000/μL, and hemoglobin > 9 g/dL
- Creatinine < 2 mg/dL
- Total bilirubin < 1 times the upper limit of normal, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 1.5 times the upper limit of normal
Who cannot join
- History of uncontrolled seizure disorder
- Clinically significant cardiovascular disease including:
- Myocardial infarction or uncontrolled angina within 6 months
- Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or patients with history of congestive heart failure NYHA class 3 or 4 in the past
- Uncontrolled hypertension as indicated by a resting systolic blood pressure > 170 mmHg or diastolic blood pressure > 105 mmHg at the screening visit
- Have used or plan to use from 30 days prior to enrollment through the end of the study medication known to lower the seizure threshold or prolong the QT interval
Show all 12Show fewer
- Major surgery within 4 weeks of enrollment
- Radiation therapy within 4 weeks of enrollment
- Prior use of abiraterone acetate, enzalutamide, docetaxel, cabazitaxel, carboplatin, or radium-223 for the treatment of castration-resistant disease
- Prior docetaxel use in the hormone-sensitive disease setting is allowed, but must be completed ≥ 4 weeks prior to enrollment
- Prior sipuleucel-T use is allowed, but must be completed ≥ 4 weeks prior to enrollment
- Concurrent use of zoledronic acid or denosumab is allowed on study
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Mount Sinai Beth Israel
New York, New York, 10011
Icahn School of Medicine at Mount Sinai
New York, New York, 10028
About this study
Official title: Clinical Trial of a Rapidly Cycling, Non-Cross Reactive Regimen of Approved Therapeutic Agents to Treat Prostate Cancer
The purpose of this study is to determine the clinical benefits of using a rapidly cycling, non-cross reactive regimen of FDA-approved prostate cancer therapeutic agents in the management of castration resistant prostate cancer. The hypothesis is that the identification of optimal combinations and sequencing of therapies can help prevent or delay the development of therapeutic drug resistance, and can be safely tolerated.
Read the detailed description
This phase II clinical trial will explore the efficacy of rapidly cycling non-cross reactive treatment therapies in the treatment of patients with newly diagnosed mCRPC. The primary hypothesis is that the best chance of eliminating or controlling disease is when the cancer is treatment naïve, and has not yet developed therapeutic resistance. By finding an optimal drug deployment strategy of already approved and available treatments for mCRPC, the researchers believe providers can more effectively treat an intrinsically heterogeneous disease, delay/prevent drug resistance, as well as minimize treatment toxicity.
All of the treatment agents selected have well-defined individual toxicity profiles from large phase III trials, but there is limited clinical data about the toxicity profiles of these drugs in combinations. While each agent is generally well tolerated, toxicities remain a significant concern given the older age of the typical mCRPC patient, the comorbid conditions common to this patient population, as well as those borne from previous chronic androgen deprivation therapy.
Each drug in the proposed treatment regimen will be used at their FDA-approved dosing and indication, with the exception of cabazitaxel, which will be used prior to disease demonstration of docetaxel failure, and in combination with carboplatin. The proposed sequencing is rationally designed, and based on each drug's distinct mechanisms of action as well as their toxicity profiles.
The rapidly-cycling treatment regimen contains three, separate, consecutive treatment modules, each lasting 3 months: 1. Abiraterone; 2. Cabazitaxel + Carboplatin; 3. Enzalutamide + Radium-223. Therapeutic agents are delivered as non-cross reactive combinations, in order to achieve optimal therapeutic dosing at each cycle and decrease possibility of significant adverse effects.
To the researcher knowledge, no study has evaluated the use of rapidly cycling, non-cross reactive therapies for the treatment of mCRPC. The hypothesis is that the identification of optimal combinations and sequencing of rapidly cycling non-cross reactive therapies can help prevent or delay the development of therapeutic drug resistance, and can be safely tolerated.
Primary objective is to evaluate the time to disease progression after completion of all modules of the rapidly-cycling, non-cross reactive regimen in patients with mCRPC. Secondary objectives are to evaluate overall survival, prostate-specific antigen (PSA) response rate with each treatment module, changes to alkaline phosphatase level, and assess safety of the rapidly-cycling, non-cross reactive regimen. Additional exploratory objective are to evaluate the correlation of a peripheral whole-blood RNA signature with clinical outcome measures during and after treatment, and to evaluate changes to AR-V7 expression in CTCs with different treatment modalities and clinical outcomes.
- Conditions
- Prostate Cancer
- Being tested
- Abiraterone acetate, Prednisone, Radium-223 dichloride, cabazitaxel, Carboplatin
- Keywords
- Castration resistant, Prostate cancer, Metastatic, First-line, Treatment naive, Rapidly cycling, Non-cross resistant
- Medical subject headings
- Prostatic Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Abiraterone acetateDrug
Abiraterone acetate 1000 mg PO daily
PrednisoneDrug
5 mg PO twice a day
Radium-223 dichlorideDrug
50 kBq/kg IV monthly
cabazitaxelDrug
25 mg/m2 IV every 3 weeks
CarboplatinDrug
Carboplatin AUC 4 IV every 3 weeks
EnzalutamideDrug
160 mg PO daily
| Study group | Role | What they receive |
|---|---|---|
| Intensive, Non-Cross Reactive Therapy | Experimental | Prostate Cancer Rapidly cycling, Intensive, Non-Cross Reactive Therapy (PRINT) Rapidly cycling, consecutive treatment modules: 1. Abiraterone acetate; 2. Cabazitaxel + Carboplatin; 3. Enzalutamide + Radium-223 Receives: Drug: Abiraterone acetate; Drug: Prednisone; Drug: Radium-223 dichloride; Drug: cabazitaxel; Drug: Carboplatin; Drug: Enzalutamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Disease Progression
Time to disease progression, as determined by either PSA or radiographic progression, after completion of all modules of the rapidly-cycling, non-cross reactive regimen in patients with mCRPC.
Time to progression (TTP) is defined as beginning with the time the first dose of PCD regimen is administered until disease progression.
Measured: 47.8 months
Secondary outcomes (7)
Overall Survival (OS)
Overall survival defined as the time of study entry to death from any cause.
Measured: 47.8 months
Overall Rate of Survival
Overall rate of survival at 40 months. Overall rate of Survival as defined by likelihood that a participant on the study is still alive at 40 months follow up
Measured: 40 months
Number of Participants With PSA Response Rate >90%
PSA response rate - >90% decrease in PSA compared to baseline
Measured: up to 36 weeks
Number of Participants With PSA Response Rate >=50%
Number of participants with PSA response rate >=50% decrease in PSA compared to baseline
Measured: up to 36 weeks
Number of Participants With PSA Progression Compared to Baseline.
PSA changes was reported globally using a waterfall plot for each module. In participants who have a decline in PSA value from baseline, progression is defined by:
- An increase in PSA by 25% above the nadir, AND
- An increase in PSA by a minimum of 2 ng/ml, or an increase in PSA to the pre-treatment PSA value, AND
- Confirmation by a second PSA at least 3 weeks apart, AND
- Occur following at least 12 weeks of therapy, AND
- There is no objective evidence of disease response.
In participants whose PSA value from baseline has not declined from baseline, progression is defined by:
- An increase in PSA by 25% above either the pre-treatment level, or the nadir PSA level (whichever is lowest), AND
- An increase in PSA by a minimum of 2 ng/ml, AND
- Confirmation by a second PSA at least 3 weeks apart, AND
- Occur following at least 12 weeks of therapy, AND
- There is no objective evidence of disease response.
Measured: up to 36 weeks
Number of Participants With Stable PSA as Compared to Baseline
Participants with a 50% PSA decline from their baseline PSA level will be considered responders, provided objective tumor measurements are stable or also demonstrate response. Participants with a 25% PSA increase from their baseline PSA will be considered nonresponders. Participants that do not meet criteria for responder or nonresponder, will be considered to have stable disease.
Measured: up to 36 weeks
Number of Participants With Normal Alkaline Phosphatase Levels
Number of participants who converted from elevated to normal range of alkaline phosphatase levels at 9 months from baseline
Measured: baseline and 36 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2016 (estimated)
- Study start13 Jan 2017
- Primary completion15 Nov 2021
- Study completion15 Nov 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by Icahn School of Medicine at Mount SinaiThe 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Icahn School of Medicine at Mount Sinai
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Bobby Liaw, Icahn School of Medicine at Mount Sinai
- Investigators
- Bobby Liaw, MD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02903160
- Sponsor's protocol ID
- GCO 16-1593
- Other IDs
- CABAZL07459, ONC-2014-168
- Status last verified
- Jan 2024
- First submitted
- 7 Sep 2016
- Last updated
- 7 Feb 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Trial of a Rapidly Cycling, Non-Cross Reactive Regimen of Approved Therapeutic Agents to Treat Prostate Cancer
- ClinicalTrials.gov ID
- NCT02903160
- Acronym / sponsor ID
- GCO 16-1593
- Conditions
- Prostate Cancer
- Keywords
- Castration resistant, Prostate cancer, Metastatic, First-line, Treatment naive, Rapidly cycling, Non-cross resistant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Icahn School of Medicine at Mount SinaiUniversity, hospital or other
- Collaborators
- Sanofi, Bayer
- Study start
- 13 Jan 2017 (actual)
- Primary completion
- 15 Nov 2021 (actual)
- Study completion
- 15 Nov 2021 (actual)
- First posted
- 16 Sep 2016 (estimated)
- Results
- Posted 7 Feb 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the clinical benefits of using a rapidly cycling, non-cross reactive regimen of FDA-approved prostate cancer therapeutic agents in the management of castration resistant prostate cancer. The hypothesis is that the identification of optimal combinations and sequencing of therapies can help prevent or delay the development of therapeutic drug resistance, and can be safely tolerated.
Detailed description
This phase II clinical trial will explore the efficacy of rapidly cycling non-cross reactive treatment therapies in the treatment of patients with newly diagnosed mCRPC. The primary hypothesis is that the best chance of eliminating or controlling disease is when the cancer is treatment naïve, and has not yet developed therapeutic resistance. By finding an optimal drug deployment strategy of already approved and available treatments for mCRPC, the researchers believe providers can more effectively treat an intrinsically heterogeneous disease, delay/prevent drug resistance, as well as minimize treatment toxicity.
All of the treatment agents selected have well-defined individual toxicity profiles from large phase III trials, but there is limited clinical data about the toxicity profiles of these drugs in combinations. While each agent is generally well tolerated, toxicities remain a significant concern given the older age of the typical mCRPC patient, the comorbid conditions common to this patient population, as well as those borne from previous chronic androgen deprivation therapy.
Each drug in the proposed treatment regimen will be used at their FDA-approved dosing and indication, with the exception of cabazitaxel, which will be used prior to disease demonstration of docetaxel failure, and in combination with carboplatin. The proposed sequencing is rationally designed, and based on each drug's distinct mechanisms of action as well as their toxicity profiles.
The rapidly-cycling treatment regimen contains three, separate, consecutive treatment modules, each lasting 3 months: 1. Abiraterone; 2. Cabazitaxel + Carboplatin; 3. Enzalutamide + Radium-223. Therapeutic agents are delivered as non-cross reactive combinations, in order to achieve optimal therapeutic dosing at each cycle and decrease possibility of significant adverse effects.
To the researcher knowledge, no study has evaluated the use of rapidly cycling, non-cross reactive therapies for the treatment of mCRPC. The hypothesis is that the identification of optimal combinations and sequencing of rapidly cycling non-cross reactive therapies can help prevent or delay the development of therapeutic drug resistance, and can be safely tolerated.
Primary objective is to evaluate the time to disease progression after completion of all modules of the rapidly-cycling, non-cross reactive regimen in patients with mCRPC. Secondary objectives are to evaluate overall survival, prostate-specific antigen (PSA) response rate with each treatment module, changes to alkaline phosphatase level, and assess safety of the rapidly-cycling, non-cross reactive regimen. Additional exploratory objective are to evaluate the correlation of a peripheral whole-blood RNA signature with clinical outcome measures during and after treatment, and to evaluate changes to AR-V7 expression in CTCs with different treatment modalities and clinical outcomes.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Intensive, Non-Cross Reactive Therapy | Experimental | Drug: Abiraterone acetate, Drug: Prednisone, Drug: Radium-223 dichloride, Drug: cabazitaxel, Drug: Carboplatin, Drug: EnzalutamideProstate Cancer Rapidly cycling, Intensive, Non-Cross Reactive Therapy (PRINT) Rapidly cycling, consecutive treatment modules: 1. Abiraterone acetate; 2. Cabazitaxel + Carboplatin; 3. Enzalutamide + Radium-223 |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Histologically or cytologically confirmed adenocarcinoma of the prostate
- Metastatic castrate resistant prostate cancer, defined by progressive disease based on either rising PSA, new bone metastases, or progression of measurable disease on standard imaging, according to PCWG2 guidelines, despite androgen deprivation therapy
- Ongoing androgen deprivation therapy with a GnRH analogue, GnRH antagonist, or bilateral orchiectomy
- ECOG performance status 0-1
- Serum testosterone level < 50 ng/dL
Key exclusion criteria (12 listed)
- History of uncontrolled seizure disorder
- Clinically significant cardiovascular disease including:
- Have used or plan to use from 30 days prior to enrollment through the end of the study medication known to lower the seizure threshold or prolong the QT interval
- Major surgery within 4 weeks of enrollment
- Radiation therapy within 4 weeks of enrollment
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 |
|---|---|---|
| Abiraterone acetateAbiraterone acetate 1000 mg PO daily | Drug | Intensive, Non-Cross Reactive Therapy |
| Prednisone5 mg PO twice a day | Drug | Intensive, Non-Cross Reactive Therapy |
| Radium-223 dichloride50 kBq/kg IV monthly | Drug | Intensive, Non-Cross Reactive Therapy |
| cabazitaxel25 mg/m2 IV every 3 weeks | Drug | Intensive, Non-Cross Reactive Therapy |
| CarboplatinCarboplatin AUC 4 IV every 3 weeks | Drug | Intensive, Non-Cross Reactive Therapy |
| Enzalutamide160 mg PO daily | Drug | Intensive, Non-Cross Reactive Therapy |
Primary outcome
Time to Disease Progression
Time frame: 47.8 months
Time to disease progression, as determined by either PSA or radiographic progression, after completion of all modules of the rapidly-cycling, non-cross reactive regimen in patients with mCRPC. Time to progression (TTP) is defined as beginning with the time the first dose of PCD regimen is administered until disease progression.
7 secondary outcomes
Overall Survival (OS)
Time frame: 47.8 months
Overall Rate of Survival
Time frame: 40 months
Number of Participants With PSA Response Rate >90%
Time frame: up to 36 weeks
Number of Participants With PSA Response Rate >=50%
Time frame: up to 36 weeks
Number of Participants With PSA Progression Compared to Baseline.
Time frame: up to 36 weeks
Number of Participants With Stable PSA as Compared to Baseline
Time frame: up to 36 weeks
Number of Participants With Normal Alkaline Phosphatase Levels
Time frame: baseline and 36 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Bobby Liaw, MD principal investigator
Icahn School of Medicine at Mount Sinai
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Abiraterone acetate, Prednisone and Radium-223 dichloride in people with Prostate Cancer, run by Icahn School of Medicine at Mount Sinai at 2 sites 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 8 inclusion and 12 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 7 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Feb 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Time to Disease Progression (time frame: 47.8 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 7 Feb 2024.