Neoplasm MalignantPhase 1NCT01140607
Safety and Pharmacokinetic Study of Cabazitaxel in Patients With Advanced Solid Tumors and Liver Impairment
A Phase 1 study testing Cabazitaxel (XRP6258) in people with Neoplasm Malignant, run by Sanofi at 14 sites in United States.
Trial summary
Primary Objectives: To determine the maximum tolerated dose (MTD) and safety of Cabazitaxel when administered to advanced solid tumor patients with varying degrees of hepatic impairment To determine the pharmacokinetics (PKs) of Cabazitaxel in patients with varying degrees of hepatic impairment To correlate PK… Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Neoplasm Malignant
- What is being tested?
- Cabazitaxel (XRP6258)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 14 sitesUnited States
- Study dates
- May 2010to Jul 2014
- 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 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Patients with a diagnosis of advanced, measurable or non-measurable, non-hematological cancer who have varying degrees of hepatic impairment. The cancer must be one that is either refractory to standard therapy or for which no standard therapy exists.
Who cannot join
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) >2
- Life expectancy <3 months
- Need for a major surgical procedure or radiation therapy during the study
- Evidence of another active malignancy
- Prior chemotherapy, other investigational drug, biological therapy, targeted non-cytotoxic therapy and radiotherapy within 3 weeks prior to registration
- Patients with known history of Gilbert's syndrome
Show all 11Show fewer
- Prior treatment with Cabazitaxel and a history of severe (Grade ≥3) hypersensitivity to taxanes, polysorbate-80, or to compounds with similar chemical structures
- Prior history of bone marrow transplant
- Any treatment known to induce CYP isoenzymes or to inhibit CYP3A4 activities within 2 weeks before or during the test period of the pharmacokinetic sampling. Moderate inhibitors within one week prior and during the pharmacokinetic sampling.
- Any contra-indications to midazolam, according to the applicable labeling.
- The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
United States14 sites
Investigational Site Number 840019
Baltimore, Maryland, 21201
Investigational Site Number 840010
Bethlehem, Pennsylvania, 18015
Investigational Site Number 840012
Boston, Massachusetts, 02115
Investigational Site Number 840021
Canton, Ohio, 44718
Investigational Site Number 840007
Cincinnati, Ohio, 45267-0542
Investigational Site Number 840017
Decatur, Illinois, 62526
Investigational Site Number 840016
Jacksonville, Florida, 32207
Investigational Site Number 840014
La Jolla, California, 92093
Investigational Site Number 840013
Loma Linda, California, 92354
Investigational Site Number 840003
Metairie, Louisiana, 70006
Investigational Site Number 840006
San Antonio, Texas, 78229
Investigational Site Number 840001
St Louis, Missouri, 63110
Investigational Site Number 840002
Tampa, Florida, 33612
Investigational Site Number 840020
Washington D.C., District of Columbia, 20037
About this study
Official title: Phase I Safety and Pharmacokinetic Study of XRP6258 (Cabazitaxel) In Advanced Solid Tumor Patients With Varying Degrees of Hepatic Impairment
Primary Objectives:
- To determine the maximum tolerated dose (MTD) and safety of Cabazitaxel when administered to advanced solid tumor patients with varying degrees of hepatic impairment
- To determine the pharmacokinetics (PKs) of Cabazitaxel in patients with varying degrees of hepatic impairment
- To correlate PK variables with pharmacodynamic (PD) safety parameters in order to guide prescribers with regard to dosing in this patient population
- To assess the effect of cabazitaxel at recommended dose of 25mg/m^2 on CYP3A enzyme activity using midazolam as probe in an additional cohort of cancer patients with normal hepatic function.
Read the detailed description
The study consists of:
- a screening phase (maximum length of 21-day).
- a treatment phase with 21-day study treatment cycles. Cycle lengths may be extended up to maximum of 12 additional days in case of unresolved toxicity.
Patients continue to receive treatment until they experience, unacceptable toxicities/AEs, disease progression ,withdraw their consent, or the investigator decides to discontinue the patient, or study cut-off, whichever comes first.
- a 30-day follow-up visit after the last dose of study medication.
The cut off date is when the last patient treated has completed cycle 1 and the subsequent 30 days follow-up.
Patients may continue to be treated as long as they are benefiting from study treatment and have not met study withdrawal criteria.
- Conditions
- Neoplasm Malignant
- Being tested
- Cabazitaxel (XRP6258)
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cabazitaxel (XRP6258)Drug
Pharmaceutical form:solution for infusion
Route of administration: intravenous
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: normal hepatic function: cabazitaxel | Experimental | cabazitaxel 25mg/m^2
IV infusion of Cabazitaxel is given over 1 hour on Day 1 of each cycle (every 3 weeks). Receives: Drug: Cabazitaxel (XRP6258) |
| Cohort 2: mild hepatic impairment : cabazitaxel | Experimental | cabazitaxel 20mg/m^2
IV infusion of Cabazitaxel is given over 1 hour on Day 1 of each cycle (every 3 weeks). Receives: Drug: Cabazitaxel (XRP6258) |
| Cohort 3: moderate hepatic impairment: cabazitaxel | Experimental | cabazitaxel 10mg/m^2
IV infusion of Cabazitaxel is given over 1 hour on Day 1 of each cycle (every 3 weeks). Receives: Drug: Cabazitaxel (XRP6258) |
| Cohort 4: severe hepatic impairment: cabazitaxel | Experimental | cabazitaxel 5 mg/m^2 or 10mg/m^2
IV infusion of Cabazitaxel is given over 1 hour on Day 1 of each cycle (every 3 weeks). Receives: Drug: Cabazitaxel (XRP6258) |
| Cohort 5: normal hepatic function: cabazitaxel and midazolam | Experimental | cabazitaxel 25mg/m^2
IV infusion of Cabazitaxel is given over 1 hour on Day 1 of each cycle (every 3 weeks).
Midazolam is given orally in single dosing on day -1 and day 1 (crossover) Receives: Drug: Cabazitaxel (XRP6258) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Dose Limiting Toxicities (DLT)
A clinical adverse event or a laboratory abnormality is defined as DLT when it is drug-related as assessed by the investigator and agreed upon by the study committee.
Measured: cycle 1 (3 weeks)
Secondary outcomes (3)
Safety investigations (physical examination, vital signs and laboratory tests)
Physical examination includes Eastern Cooperative Oncology Group (ECOG) performance status and signs and symptoms.
Vital signs includes weight, temperature, blood pressure and heart rate.
Laboratory tests includes hematology, coagulation, biochemistry and urinalysis. Laboratory abnormalities are graded according to the NCI CTCAE v.4.0
Measured: up to 30 days after the last dosing
Pharmacokinetic profile of Cabazitaxel (AUC, Cmax, t1/2, CL, and Vss) from plasma concentration
Measured: cycle 1 (3 weeks)
Cabazitaxel effect on CYP3A enzyme activity
Measured: single dosing on day -1 and day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2010 (estimated)
- Study startMay 2010
- Primary completionJul 2014
- Study completionJul 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neoplasm MalignantStudies of the same condition, open and under way.
- More trials run by SanofiThe 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
- Single group
- Masking
- None (open label)
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, Study director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01140607
- Sponsor's protocol ID
- POP6792
- Other IDs
- U1111-1116-5845
- Status last verified
- Jul 2015
- First submitted
- 28 May 2010
- Last updated
- 21 Jul 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Safety and Pharmacokinetic Study of XRP6258 (Cabazitaxel) In Advanced Solid Tumor Patients With Varying Degrees of Hepatic Impairment
- ClinicalTrials.gov ID
- NCT01140607
- Acronym / sponsor ID
- POP6792
- Conditions
- Neoplasm Malignant
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Study start
- May 2010
- Primary completion
- Jul 2014 (actual)
- Study completion
- Jul 2014 (actual)
- First posted
- 9 Jun 2010 (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.
Primary Objectives:
- To determine the maximum tolerated dose (MTD) and safety of Cabazitaxel when administered to advanced solid tumor patients with varying degrees of hepatic impairment
- To determine the pharmacokinetics (PKs) of Cabazitaxel in patients with varying degrees of hepatic impairment
- To correlate PK variables with pharmacodynamic (PD) safety parameters in order to guide prescribers with regard to dosing in this patient population
- To assess the effect of cabazitaxel at recommended dose of 25mg/m^2 on CYP3A enzyme activity using midazolam as probe in an additional cohort of cancer patients with normal hepatic function.
Detailed description
The study consists of:
- a screening phase (maximum length of 21-day).
- a treatment phase with 21-day study treatment cycles. Cycle lengths may be extended up to maximum of 12 additional days in case of unresolved toxicity.
Patients continue to receive treatment until they experience, unacceptable toxicities/AEs, disease progression ,withdraw their consent, or the investigator decides to discontinue the patient, or study cut-off, whichever comes first.
- a 30-day follow-up visit after the last dose of study medication.
The cut off date is when the last patient treated has completed cycle 1 and the subsequent 30 days follow-up.
Patients may continue to be treated as long as they are benefiting from study treatment and have not met study withdrawal criteria.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: normal hepatic function: cabazitaxel | Experimental | Drug: Cabazitaxel (XRP6258)cabazitaxel 25mg/m^2 IV infusion of Cabazitaxel is given over 1 hour on Day 1 of each cycle (every 3 weeks). |
| Cohort 2: mild hepatic impairment : cabazitaxel | Experimental | Drug: Cabazitaxel (XRP6258)cabazitaxel 20mg/m^2 IV infusion of Cabazitaxel is given over 1 hour on Day 1 of each cycle (every 3 weeks). |
| Cohort 3: moderate hepatic impairment: cabazitaxel | Experimental | Drug: Cabazitaxel (XRP6258)cabazitaxel 10mg/m^2 IV infusion of Cabazitaxel is given over 1 hour on Day 1 of each cycle (every 3 weeks). |
| Cohort 4: severe hepatic impairment: cabazitaxel | Experimental | Drug: Cabazitaxel (XRP6258)cabazitaxel 5 mg/m^2 or 10mg/m^2 IV infusion of Cabazitaxel is given over 1 hour on Day 1 of each cycle (every 3 weeks). |
| Cohort 5: normal hepatic function: cabazitaxel and midazolam | Experimental | Drug: Cabazitaxel (XRP6258)cabazitaxel 25mg/m^2 IV infusion of Cabazitaxel is given over 1 hour on Day 1 of each cycle (every 3 weeks). Midazolam is given orally in single dosing on day -1 and day 1 (crossover) |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Patients with a diagnosis of advanced, measurable or non-measurable, non-hematological cancer who have varying degrees of hepatic impairment. The cancer must be one that is either refractory to standard therapy or for which no standard therapy exists.
Key exclusion criteria (11 listed)
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) >2
- Life expectancy <3 months
- Need for a major surgical procedure or radiation therapy during the study
- Evidence of another active malignancy
- Prior chemotherapy, other investigational drug, biological therapy, targeted non-cytotoxic therapy and radiotherapy within 3 weeks prior to registration
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 |
|---|---|---|
| Cabazitaxel (XRP6258)Pharmaceutical form:solution for infusion Route of administration: intravenous | Drug | Cohort 1: normal hepatic function: cabazitaxel, Cohort 2: mild hepatic impairment : cabazitaxel, Cohort 3: moderate hepatic impairment: cabazitaxel, Cohort 4: severe hepatic impairment: cabazitaxel, Cohort 5: normal hepatic function: cabazitaxel and midazolam |
Primary outcome
Incidence of Dose Limiting Toxicities (DLT)
Time frame: cycle 1 (3 weeks)
A clinical adverse event or a laboratory abnormality is defined as DLT when it is drug-related as assessed by the investigator and agreed upon by the study committee.
3 secondary outcomes
Safety investigations (physical examination, vital signs and laboratory tests)
Time frame: up to 30 days after the last dosing
Pharmacokinetic profile of Cabazitaxel (AUC, Cmax, t1/2, CL, and Vss) from plasma concentration
Time frame: cycle 1 (3 weeks)
Cabazitaxel effect on CYP3A enzyme activity
Time frame: single dosing on day -1 and day 1
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 21 Jul 2015.
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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.
Clinical Sciences & Operations study director
Sanofi
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Cabazitaxel (XRP6258) in people with Neoplasm Malignant, run by Sanofi at 14 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 1 inclusion and 11 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 21 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 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 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 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?
Incidence of Dose Limiting Toxicities (DLT) (time frame: cycle 1 (3 weeks)). 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 21 Jul 2015.