Prostate CancerPhase 1NCT03043989
Cohorts of Docetaxel or Cabazitaxel in Combination With the Potent CYP3A4 Inhibitor, Clarithromycin
A Phase 1 study testing Docetaxel, Cabazitaxel and Clarithromycin in people with Prostate Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
Trial summary
This clinical trial is being conducted to recommend a safe and tolerable phase 2 dose of docetaxel or cabazitaxel when combined with clarithromycin in men who have developed castrate-resistant prostate cancer. In the castrate-resistant setting, resistance to taxane therapy inevitably develops. 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?
- Docetaxel, Cabazitaxel and Clarithromycin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Mar 2017to 26 Jul 2019
- Phase
- Phase 1
- 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
- Men with metastatic castrate-resistant prostate cancer (prostate cancer progressing despite castrate levels of testosterone <50 ng/dL), using standard measures of progression defined by PCWG2
- Have received at least 4 cycles of docetaxel or cabazitaxel, and less than ten, with two consecutive rising PSA values, checked at least 7 days apart. No PSA decline in last 42 day
- Bone disease documented by either: a positive bone scan, CT scan, or MRI; or biopsy-proven bony metastases
- Age ≥18 years
- ECOG performance status ≤ 2 (Karnofsky ≥ 60%)
- Have normal organ and marrow function defined as:
Show all 15Show fewer
- absolute neutrophil count ≥1,500/mcL
- platelets ≥100,000/mcL
- total bilirubin (within normal institutional limits)
- AST/ALT ≤ 2.5 × ULN (or ≤ 1.5 x ULN in conjunction with alk phos >2.5 x ULN for Docetaxel
- AST ≤ 1.5 x ULN for Cabazitaxel
- creatinine clearance-no minimum for Docetaxel
- creatinine clearance- ≥ 30 mL/min/1.73 m2 for Cabazitaxel
- No evidence of clinical progression, in the form of increased lesions on cross-sectional imaging, or new cancer-attributable symptoms or worsening of existing symptoms
- Ability to understand and the willingness to sign a written informed consent document
Who cannot join
- Patients who have residual toxicities > Grade 2 attributed to taxane therapy, except for neuropathy, who are excluded if > grade 1
- Patients who are receiving any other investigational agents or have within the last 28 day.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to clarithromycin or taxanes
- Patients receiving any medications or substances that are inhibitors or inducers of CYP3A4 are ineligible
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Received more than 10 cycles of docetaxel [for docetaxel cohort only] or 6 of cabazitaxel [for cabazitaxel cohort only]
- Last docetaxel or cabazitaxel dose > 6 weeks prior to enrollment
- Patients with a documented history of QT prolongation or ventricular cardiac arrhythmia, including torsades de pointes, or taking drugs that are known to prolong the QT
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Two Independent Phase 1b Cohorts of Docetaxel or Cabazitaxel in Combination With the Potent CYP3A4 Inhibitor, Clarithromycin
This clinical trial is being conducted to recommend a safe and tolerable phase 2 dose of docetaxel or cabazitaxel when combined with clarithromycin in men who have developed castrate-resistant prostate cancer.
In the castrate-resistant setting, resistance to taxane therapy inevitably develops. Men who develop resistance to taxanes have a very poor prognosis, and few treatment options.
It is believed that CYP enzymes contribute to docetaxel and cabazitaxel resistance in metastatic prostate cancer, and this resistance can be mitigated through pharmacologic CYP inhibition. In this study a potent CYP3A inhibitor, clarithromycin, will be co-administered concurrently with either docetaxel or cabazitaxel, whose systemic metabolism is dependent of CYP3A4, with the intent to overcome resistance to taxanes.
Read the detailed description
This is a dose-escalation study designed to determine the maximum tolerated dose of docetaxel or cabazitaxel when given in combination with clarithromycin. Eligible patients will be assigned to docetaxel or cabazitaxel, based on which drug they were previously administered prior to study entry. Enrollment to dose levels will be in a 3+3 cohort design until the maximum tolerated dose is achieved.
Docetaxel or cabazitaxel will be administered on day 1 of each (3 week) cycle for a total of 6 cycles. Subjects in both arms will be administered clarithromycin on days -1, 1 and 2 of each 3 week cycle.
- Conditions
- Prostate Cancer
- Being tested
- Docetaxel, Cabazitaxel, Clarithromycin
- Keywords
- docetaxel, cabazitaxel, phase 1b, castration-resistant, bone metastasis
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DocetaxelDrug
6 infusions of Docetaxel with 18 doses clarithromycin
CabazitaxelDrug
Also called JEVTANA
6 infusions of Cabazitaxel with 18 doses clarithromycin
ClarithromycinDrug
18 doses of clarithromycin with either Docetaxel or Cabazitaxel
| Study group | Role | What they receive |
|---|---|---|
| Docetaxel and clarithromycin combination | Active comparator | Docetaxel will be administered by intravenous infusion over 1 hour every 3 weeks on day 1 of each (3 week) cycle for a total of 18 weeks.
Clarithromycin will be administered orally at 500mg twice a day for 3 days per cycle on days -1, 1, and 2. Receives: Drug: Docetaxel; Drug: Clarithromycin |
| Cabazitaxel and clarithromycin combination | Active comparator | Cabazitaxel will be administered by intravenous infusion over 1 hour every 3 weeks on day 1 of each (3 week) cycle for a total of 18 weeks.
Clarithromycin will be administered orally at 500mg twice a day for 3 days per cycle on days -1, 1, and 2. Receives: Drug: Cabazitaxel; Drug: Clarithromycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Measured: 3 years
Escalate dose up the maximum tolerated dose achieved, and initiate this as the recommended phase 2 dose of docetaxel and of cabazitaxel when it is combined with clarithromycin.
Measured: 3 years
Secondary outcomes (2)
Compare docetaxel OR cabazitaxel exposure (maximal [Cmax] when combined with the strong CYP3A4 inhibitor clarithromycin to historic controls.
Measured: 3 years
Compare docetaxel OR cabazitaxel exposure ( total [AUC]) when combined with the strong CYP3A4 inhibitor clarithromycin to historic controls.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2017 (estimated)
- Study start21 Mar 2017
- Primary completion26 Jul 2019
- Study completion26 Jul 2019
Why it stopped: Low accrual
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 Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Maryland Technology Development Corporation
- Responsible party
- Sponsor
- Investigators
- Michael A Carducci, MD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03043989
- Sponsor's protocol ID
- J16144
- Other IDs
- IRB00117591
- Status last verified
- Feb 2020
- First submitted
- 26 Jan 2017
- Last updated
- 17 Feb 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Two Independent Phase 1b Cohorts of Docetaxel or Cabazitaxel in Combination With the Potent CYP3A4 Inhibitor, Clarithromycin
- ClinicalTrials.gov ID
- NCT03043989
- Acronym / sponsor ID
- J16144
- Conditions
- Prostate Cancer
- Keywords
- docetaxel, cabazitaxel, phase 1b, castration-resistant, bone metastasis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low accrual
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
- Collaborators
- Maryland Technology Development Corporation
- Study start
- 21 Mar 2017 (actual)
- Primary completion
- 26 Jul 2019 (actual)
- Study completion
- 26 Jul 2019 (actual)
- First posted
- 6 Feb 2017 (estimated)
- 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 clinical trial is being conducted to recommend a safe and tolerable phase 2 dose of docetaxel or cabazitaxel when combined with clarithromycin in men who have developed castrate-resistant prostate cancer.
In the castrate-resistant setting, resistance to taxane therapy inevitably develops. Men who develop resistance to taxanes have a very poor prognosis, and few treatment options.
It is believed that CYP enzymes contribute to docetaxel and cabazitaxel resistance in metastatic prostate cancer, and this resistance can be mitigated through pharmacologic CYP inhibition. In this study a potent CYP3A inhibitor, clarithromycin, will be co-administered concurrently with either docetaxel or cabazitaxel, whose systemic metabolism is dependent of CYP3A4, with the intent to overcome resistance to taxanes.
Detailed description
This is a dose-escalation study designed to determine the maximum tolerated dose of docetaxel or cabazitaxel when given in combination with clarithromycin. Eligible patients will be assigned to docetaxel or cabazitaxel, based on which drug they were previously administered prior to study entry. Enrollment to dose levels will be in a 3+3 cohort design until the maximum tolerated dose is achieved.
Docetaxel or cabazitaxel will be administered on day 1 of each (3 week) cycle for a total of 6 cycles. Subjects in both arms will be administered clarithromycin on days -1, 1 and 2 of each 3 week cycle.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Docetaxel and clarithromycin combination | Active comparator | Drug: Docetaxel, Drug: ClarithromycinDocetaxel will be administered by intravenous infusion over 1 hour every 3 weeks on day 1 of each (3 week) cycle for a total of 18 weeks. Clarithromycin will be administered orally at 500mg twice a day for 3 days per cycle on days -1, 1, and 2. |
| Cabazitaxel and clarithromycin combination | Active comparator | Drug: Cabazitaxel, Drug: ClarithromycinCabazitaxel will be administered by intravenous infusion over 1 hour every 3 weeks on day 1 of each (3 week) cycle for a total of 18 weeks. Clarithromycin will be administered orally at 500mg twice a day for 3 days per cycle on days -1, 1, and 2. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Men with metastatic castrate-resistant prostate cancer (prostate cancer progressing despite castrate levels of testosterone <50 ng/dL), using standard measures of progression defined by PCWG2
- Have received at least 4 cycles of docetaxel or cabazitaxel, and less than ten, with two consecutive rising PSA values, checked at least 7 days apart. No PSA decline in last 42 day
- Bone disease documented by either: a positive bone scan, CT scan, or MRI; or biopsy-proven bony metastases
- Age ≥18 years
- ECOG performance status ≤ 2 (Karnofsky ≥ 60%)
Key exclusion criteria (8 listed)
- Patients who have residual toxicities > Grade 2 attributed to taxane therapy, except for neuropathy, who are excluded if > grade 1
- Patients who are receiving any other investigational agents or have within the last 28 day.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to clarithromycin or taxanes
- Patients receiving any medications or substances that are inhibitors or inducers of CYP3A4 are ineligible
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
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 |
|---|---|---|
| Docetaxel6 infusions of Docetaxel with 18 doses clarithromycin | Drug | Docetaxel and clarithromycin combination |
| CabazitaxelAlso: JEVTANA6 infusions of Cabazitaxel with 18 doses clarithromycin | Drug | Cabazitaxel and clarithromycin combination |
| Clarithromycin18 doses of clarithromycin with either Docetaxel or Cabazitaxel | Drug | Cabazitaxel and clarithromycin combination, Docetaxel and clarithromycin combination |
Primary outcome
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: 3 years
Escalate dose up the maximum tolerated dose achieved, and initiate this as the recommended phase 2 dose of docetaxel and of cabazitaxel when it is combined with clarithromycin.
Time frame: 3 years
2 secondary outcomes
Compare docetaxel OR cabazitaxel exposure (maximal [Cmax] when combined with the strong CYP3A4 inhibitor clarithromycin to historic controls.
Time frame: 3 years
Compare docetaxel OR cabazitaxel exposure ( total [AUC]) when combined with the strong CYP3A4 inhibitor clarithromycin to historic controls.
Time frame: 3 years
Results and safety
The study was stopped early (reason given: Low accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2020.
- 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 A Carducci, MD principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Docetaxel, Cabazitaxel and Clarithromycin in people with Prostate Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins 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 15 inclusion and 8 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: stopped early, as of the sponsor's last update on 17 Feb 2020. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Low accrual). 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?
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 (time frame: 3 years). The study lists 2 primary outcomes in all. 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 Feb 2020.