Circulating Tumor CellPhase 2CABA-V7NCT03050866
Cabazitaxel in mCRPC Patients With AR-V7 Positive Circulating Tumor Cells (CTCs)
A Phase 2 study testing Cabazitaxel, Antihistamine and Corticosteroid in people with Circulating Tumor Cell and Metastatic Prostate Cancer, run by Erasmus Medical Center at 9 sites in Netherlands.
Trial summary
After failure on docetaxel, which has been the standard first line therapy for patients with metastatic castration-resistant prostate cancer (mCRPC), several treatment options are currently available. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Circulating Tumor Cell, Metastatic Prostate Cancer
- What is being tested?
- Cabazitaxel, Antihistamine and Corticosteroid
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 140 participants
- Where
- 9 sitesNetherlands
- Study dates
- 21 Feb 2017to 19 Aug 2022
- Phase
- Phase 2
- 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
Who may be able to join
- Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features.
- Continued androgen deprivation therapy either by luteinizing hormone-releasing hormone (LHRH) agonists/antagonists or orchiectomy.
- Serum testosterone <50 ng/mL (1.7 nmol/L) within 21 days before prescreening.
- Age ≥18 years
- Received prior docetaxel, and experienced disease progression during or after treatment with docetaxel.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (appendix A)
- Written informed consent according to ICH-GCP (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use - Good Clinical Practice) before study treatment and any study specific procedures
Who cannot join
- Geographical, psychological or other non-medical conditions interfering with follow-up
- Uncontrolled severe illness or medical condition (including uncontrolled diabetes mellitus or active systemic or local bacterial, viral, fungal - or yeast infection)
- Symptomatic central nervous system (CNS) metastases or history of psychiatric disorder that would prohibit the understanding and giving of informed consent.
- Chemotherapy or immunotherapy (other than LHRH analogues) within the last 4 weeks before study inclusion.
- Prior treatment with cabazitaxel
- Treatment with both abiraterone and enzalutamide in the post-docetaxel setting
Show all 14Show fewer
- Radiotherapy to 40% or more of the bone marrow
- Known hypersensitivity to corticosteroids
- History of severe hypersensitivity reaction (≥grade 3) to docetaxel
- History of severe hypersensitivity reaction (≥grade 3) to polysorbate 80 containing drugs
- Concurrent or planned treatment with strong inhibitors or strong inducers of cytochrome P450 3A4/5 (a one week wash-out period is necessary for patients who are already on these treatments)
- Concomitant vaccination with yellow fever vaccine
- Abnormal liver functions
- Abnormal hematological blood counts
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
Netherlands9 sites
Reinier de Graaf Groep
Delft
Admiraal de Ruyter Ziekenhuis
Flushing
Groene Hart Ziekenhuis
Gouda
Canisius Wilhelmina Ziekenhuis
Nijmegen
Erasmus MC
Rotterdam
Franciscus Gasthuis en Vlietland
Rotterdam
Maasstad Ziekenhuis
Rotterdam
Medisch Centrum Haaglanden
The Hague
Tweesteden Ziekenhuid
Tilburg
About this study
Official title: A Single Arm Phase 2 Multicenter Study Determining the Response to Cabazitaxel in Metastatic Prostate Cancer (mCRPC) Patients With AR-V7 Positive Circulating Tumor Cells (CTCs)
After failure on docetaxel, which has been the standard first line therapy for patients with metastatic castration-resistant prostate cancer (mCRPC), several treatment options are currently available.
In retrospective studies, resistance has been described to two of the treatment options, enzalutamide and abiraterone, when a splice variant of the Androgen Receptor (AR-V7) is present on circulating tumor cells (CTCs). The investigators hypothesize that patients with AR-V7 positive CTCs do have a meaningful response to cabazitaxel.
Read the detailed description
After failure on docetaxel, which has been the standard first line therapy for patients with metastatic castration-resistant prostate cancer (mCRPC), several treatment options are currently available.
Two of the treatment options are directed against the androgen receptor (AR), enzalutamide and abiraterone. A third option is cabazitaxel, a next generation taxane. No head-to-head comparisons have been done for these three therapies in second-line mCRPC and as of yet, the optimal choice is unknown.
Resistance to the AR-targeted therapies is at least in part a consequence of signaling through constitutively active AR splice variants (AR-Vs). Because AR splice variants only occur after conversion to a castration-resistant tumor, and can be acquired during systemic therapy for mCRPC, analysis of the castration-naïve primary tumor is not informative in the setting of second-line treatment of mCRPC.
Circulating tumor cells (CTCs) can be analyzed repetitively and in real-time. Recently, AR-V7 messenger ribonucleid acid (mRNA) expression in CTCs was shown to be associated with lack of response to AR-targeted therapy (reference 1). AR-V7 mRNA expression does not seem to hinder response to cabazitaxel in our retrospective pilot study (reference 2) nor in two recently published retrospective studies (reference 3 and reference 4).
Therefore we hypothesize that the mRNA expression of AR-V7 in CTCs assessed before start of second-line treatment for mCRPC does not affect prostate-specific antigen (PSA) response to cabazitaxel in patients who have progressed to docetaxel.
Patients who are eligible to undergo second or third line treatment will be asked to undergo prescreening consisting of a CTC count and, in case ≥3 CTCs are detected, AR V7 determination. Patients with ≥3 CTCs with AR-V7 expression will be asked to sign a second informed consent to enter the treatment study. In this study they will receive Cabazitaxel 25 mg/m² every 3 weeks plus prednisone 10 mg daily, and undergo repeated blood sampling for biomarker sample collection.
During the prescreening in all patients, 2 x 10 mL blood will be drawn for enumeration and isolation of CTCs. All patients with ≥3 CTCs with AR-V7 expression will be asked to sign consent for the treatment study.
All patients included in the treatment study will be administrated cabazitaxel intravenously at a dose of 25 mg/m², during a one-hour infusion every 3 weeks, as well as continuous treatment with prednisone 5 mg orally twice daily, or 10 mg once daily. In the treatment study patients, an additional 2 x 10 mL blood will be drawn after the third cycle of treatment for CTC enumeration and isolation. An additional 10 mL blood will be drawn for storage of plasma at baseline and before start of every cycle (i.e., every 3 weeks) for analysis of cell-free DNA (cfDNA). Moreover, 4 x 5 mL blood (baseline; end of infusion, 2 and 6 hours after end of the first cabazitaxel infusion) will be drawn for pharmacokinetic studies, in order to explore a cabazitaxel exposure effect relation.
- Conditions
- Circulating Tumor Cell, Metastatic Prostate Cancer
- Being tested
- Cabazitaxel, Antihistamine, Corticosteroid, H2 antagonist, Antiemetic
- Keywords
- Androgen Receptor, AR-V7, Predictive Factor
- Medical subject headings
- Neoplastic Cells, Circulating, Prostatic Neoplasms, Bulbo-Spinal Atrophy, X-Linked
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CabazitaxelDrug
Also called Jevtana
25mg/m2 q3w
AntihistamineOther
As intravenous premedication (dexchlorpheniramine 5 mg, diphenhydramine 25 mg, or equivalent)
CorticosteroidOther
As intravenous premedication (dexamethasone 8 mg or equivalent)
H2 antagonistOther
Also called histamine H2 receptors blockers
As intravenous premedication (ranitidine or equivalent)
AntiemeticOther
Antiemetic prophylaxis is recommended and can be given orally or intravenously if necessary
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Other | Treatment intervention with Cabazitaxel with premedication as necessary (antihistamine, corticosteroid, H2 antagonist, antiemetic prophylaxis) Receives: Drug: Cabazitaxel; Other: Antihistamine; Other: Corticosteroid; Other: H2 antagonist; Other: Antiemetic |
What is being measured
The primary outcome is the main question the study is designed to answer.
PSA response
The primary endpoint is PSA response, defined as a ≥50% PSA decline from baseline during therapy.
Measured: 12 weeks after start of treatment
Secondary outcomes (10)
CTC response
CTC response defined as a decrease from ≥5 CTCs per 7.5 mL blood at baseline to <5 CTCs per 7.5 mL blood
Measured: 9-12 weeks after start of treatment
PSA change
PSA change from baseline at 12 weeks defined as the percent change in PSA from baseline at 12 weeks, according to PCWG2 criteria
Measured: 12 weeks after start of treatment
PSA decrease
Maximum PSA decrease defined according to PCWG2 criteria
Measured: PSA will be assessed at baseline, every 3 weeks during study treatment (before every cycle), and in case of study treatment discontinuation without progression every 3 months until progression, death, whichever comes first
Progression free survival
Progression-free survival (PFS) defined as time from prescreening to the date of the first documentation of disease progression (PCWG2)
Measured: Until end of study, which is anticipated to be 4 years after inclusion of first patient. If progression is not observed during the study, data on PFS will be censored
Overall survival
Overall survival (OS) calculated from the date of prescreening to death due to any cause
Measured: Until end of study, which is anticipated to be 4 years after inclusion of first patient. If death is not observed during the study, data on OS will be censored at the date patient is known to be alive or at the cut-off date, whichever comes first
Adverse Events
Grade 3-4 adverse events (AEs) and serious adverse events (SAEs) during cabazitaxel according to CTCAE v4.03 in second and third-line treatment
Measured: Until 30 days after end of treatment, Cabazitaxel treatment will consist of a maximum 10 cycles Cabazitaxel (given once every 3 weeks if there are no delays)
Cumulative dose Cabazitaxel
Cumulative administered dose of cabazitaxel in second and third-line treatment
Measured: Until last day of administration of study medication (Cabazitaxel), Cabazitaxel treatment will consist of a maximum 10 cycles Cabazitaxel (given once every 3 weeks if there are no delays)
Splice variants
AR-V7 mRNA expression as well as mRNA expression of other splice variants in CTCs indicated as absent (-) or present (+)
Measured: Splice variant will be compared before and after cabazitaxel treatment in AR-V7 positive patients, as well as before start of enzalutamide or abiraterone and after disease progression to this treatment.
Total systemic exposure
Cabazitaxel concentration in the blood and total systemic exposure to cabazitaxel, measured by the calculated area under the curve (AUC)
Measured: After infusion of first cycle of study treatment (Cabazitaxel)
Value ctDNA quantification
To explore the value of ctDNA quantification during cabazitaxel treatment to predict tumor progression
Measured: Until end of study, which is anticipated to be 4 years after inclusion of first patient
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2017
- Study start21 Feb 2017
- Primary completion1 Jan 2022 (estimated)
- Study completion19 Aug 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Circulating Tumor CellStudies of the same condition, open and under way.
- More trials run by Erasmus Medical CenterThe 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
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 140 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Erasmus Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Sanofi
- Responsible party
- Principal investigator, M.P.J.K. Lolkema, Erasmus Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03050866
- Sponsor's protocol ID
- NL58639.056.16
- Acronym
- CABA-V7
- Status last verified
- Aug 2021
- First submitted
- 7 Feb 2017
- Last updated
- 20 Aug 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Information can be shared by importing it into another databases
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Arm Phase 2 Multicenter Study Determining the Response to Cabazitaxel in Metastatic Prostate Cancer (mCRPC) Patients With AR-V7 Positive Circulating Tumor Cells (CTCs)
- ClinicalTrials.gov ID
- NCT03050866
- Acronym / sponsor ID
- CABA-V7 / NL58639.056.16
- Conditions
- Circulating Tumor Cell, Metastatic Prostate Cancer
- Keywords
- Androgen Receptor, AR-V7, Predictive Factor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 140 participants (estimated)
- Lead sponsor
- Erasmus Medical CenterUniversity, hospital or other
- Collaborators
- Sanofi
- Study start
- 21 Feb 2017 (actual)
- Primary completion
- 1 Jan 2022 (estimated)
- Study completion
- 19 Aug 2022 (estimated)
- First posted
- 13 Feb 2017 (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.
After failure on docetaxel, which has been the standard first line therapy for patients with metastatic castration-resistant prostate cancer (mCRPC), several treatment options are currently available.
In retrospective studies, resistance has been described to two of the treatment options, enzalutamide and abiraterone, when a splice variant of the Androgen Receptor (AR-V7) is present on circulating tumor cells (CTCs). The investigators hypothesize that patients with AR-V7 positive CTCs do have a meaningful response to cabazitaxel.
Detailed description
After failure on docetaxel, which has been the standard first line therapy for patients with metastatic castration-resistant prostate cancer (mCRPC), several treatment options are currently available.
Two of the treatment options are directed against the androgen receptor (AR), enzalutamide and abiraterone. A third option is cabazitaxel, a next generation taxane. No head-to-head comparisons have been done for these three therapies in second-line mCRPC and as of yet, the optimal choice is unknown.
Resistance to the AR-targeted therapies is at least in part a consequence of signaling through constitutively active AR splice variants (AR-Vs). Because AR splice variants only occur after conversion to a castration-resistant tumor, and can be acquired during systemic therapy for mCRPC, analysis of the castration-naïve primary tumor is not informative in the setting of second-line treatment of mCRPC.
Circulating tumor cells (CTCs) can be analyzed repetitively and in real-time. Recently, AR-V7 messenger ribonucleid acid (mRNA) expression in CTCs was shown to be associated with lack of response to AR-targeted therapy (reference 1). AR-V7 mRNA expression does not seem to hinder response to cabazitaxel in our retrospective pilot study (reference 2) nor in two recently published retrospective studies (reference 3 and reference 4).
Therefore we hypothesize that the mRNA expression of AR-V7 in CTCs assessed before start of second-line treatment for mCRPC does not affect prostate-specific antigen (PSA) response to cabazitaxel in patients who have progressed to docetaxel.
Patients who are eligible to undergo second or third line treatment will be asked to undergo prescreening consisting of a CTC count and, in case ≥3 CTCs are detected, AR V7 determination. Patients with ≥3 CTCs with AR-V7 expression will be asked to sign a second informed consent to enter the treatment study. In this study they will receive Cabazitaxel 25 mg/m² every 3 weeks plus prednisone 10 mg daily, and undergo repeated blood sampling for biomarker sample collection.
During the prescreening in all patients, 2 x 10 mL blood will be drawn for enumeration and isolation of CTCs. All patients with ≥3 CTCs with AR-V7 expression will be asked to sign consent for the treatment study.
All patients included in the treatment study will be administrated cabazitaxel intravenously at a dose of 25 mg/m², during a one-hour infusion every 3 weeks, as well as continuous treatment with prednisone 5 mg orally twice daily, or 10 mg once daily. In the treatment study patients, an additional 2 x 10 mL blood will be drawn after the third cycle of treatment for CTC enumeration and isolation. An additional 10 mL blood will be drawn for storage of plasma at baseline and before start of every cycle (i.e., every 3 weeks) for analysis of cell-free DNA (cfDNA). Moreover, 4 x 5 mL blood (baseline; end of infusion, 2 and 6 hours after end of the first cabazitaxel infusion) will be drawn for pharmacokinetic studies, in order to explore a cabazitaxel exposure effect relation.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Other | Drug: Cabazitaxel, Other: Antihistamine, Other: Corticosteroid, Other: H2 antagonist, Other: AntiemeticTreatment intervention with Cabazitaxel with premedication as necessary (antihistamine, corticosteroid, H2 antagonist, antiemetic prophylaxis) |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features.
- Continued androgen deprivation therapy either by luteinizing hormone-releasing hormone (LHRH) agonists/antagonists or orchiectomy.
- Serum testosterone <50 ng/mL (1.7 nmol/L) within 21 days before prescreening.
- Age ≥18 years
- Received prior docetaxel, and experienced disease progression during or after treatment with docetaxel.
Key exclusion criteria (14 listed)
- Geographical, psychological or other non-medical conditions interfering with follow-up
- Uncontrolled severe illness or medical condition (including uncontrolled diabetes mellitus or active systemic or local bacterial, viral, fungal - or yeast infection)
- Symptomatic central nervous system (CNS) metastases or history of psychiatric disorder that would prohibit the understanding and giving of informed consent.
- Chemotherapy or immunotherapy (other than LHRH analogues) within the last 4 weeks before study inclusion.
- Prior treatment with cabazitaxel
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 |
|---|---|---|
| CabazitaxelAlso: Jevtana25mg/m2 q3w | Drug | Treatment |
| AntihistamineAs intravenous premedication (dexchlorpheniramine 5 mg, diphenhydramine 25 mg, or equivalent) | Other | Treatment |
| CorticosteroidAs intravenous premedication (dexamethasone 8 mg or equivalent) | Other | Treatment |
| H2 antagonistAlso: histamine H2 receptors blockersAs intravenous premedication (ranitidine or equivalent) | Other | Treatment |
| AntiemeticAntiemetic prophylaxis is recommended and can be given orally or intravenously if necessary | Other | Treatment |
Primary outcome
PSA response
Time frame: 12 weeks after start of treatment
The primary endpoint is PSA response, defined as a ≥50% PSA decline from baseline during therapy.
10 secondary outcomes
CTC response
Time frame: 9-12 weeks after start of treatment
PSA change
Time frame: 12 weeks after start of treatment
PSA decrease
Time frame: PSA will be assessed at baseline, every 3 weeks during study treatment (before every cycle), and in case of study treatment discontinuation without progression every 3 months until progression, death, whichever comes first
Progression free survival
Time frame: Until end of study, which is anticipated to be 4 years after inclusion of first patient. If progression is not observed during the study, data on PFS will be censored
Overall survival
Time frame: Until end of study, which is anticipated to be 4 years after inclusion of first patient. If death is not observed during the study, data on OS will be censored at the date patient is known to be alive or at the cut-off date, whichever comes first
Adverse Events
Time frame: Until 30 days after end of treatment, Cabazitaxel treatment will consist of a maximum 10 cycles Cabazitaxel (given once every 3 weeks if there are no delays)
Cumulative dose Cabazitaxel
Time frame: Until last day of administration of study medication (Cabazitaxel), Cabazitaxel treatment will consist of a maximum 10 cycles Cabazitaxel (given once every 3 weeks if there are no delays)
Splice variants
Time frame: Splice variant will be compared before and after cabazitaxel treatment in AR-V7 positive patients, as well as before start of enzalutamide or abiraterone and after disease progression to this treatment.
Total systemic exposure
Time frame: After infusion of first cycle of study treatment (Cabazitaxel)
Value ctDNA quantification
Time frame: Until end of study, which is anticipated to be 4 years after inclusion of first patient
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2021.
- Individual participant dataSharing planned: Undecided. Information can be shared by importing it into another databases
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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.
The record lists no contact. Use the official record to reach the sponsor.
9 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 Cabazitaxel, Antihistamine and Corticosteroid in people with Circulating Tumor Cell and Metastatic Prostate Cancer, run by Erasmus Medical Center at 9 sites in Netherlands.
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 7 inclusion and 14 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: status not confirmed, as of the sponsor's last update on 20 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Netherlands. 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?
Results are not available in the source record.
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?
PSA response (time frame: 12 weeks after start of treatment). 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 20 Aug 2021.