Malignant Solid Tumor - Malignant Nervous System NeoplasmPhase 1/2NCT01751308
Safety and Efficacy of Cabazitaxel in Pediatric Patients With Refractory Solid Tumors Including Central Nervous System Tumors
A Phase 1/2 study testing Cabazitaxel (XRP6258) in people with Malignant Solid Tumor - Malignant Nervous System Neoplasm, run by Sanofi at 13 sites in 2 countries.
Trial summary
Primary Objectives: Phase 1 Part: To determine the dose limiting toxicity (DLT) and the maximum tolerated dose (MTD) of cabazitaxel as a single agent in pediatric participants with recurrent or refractory solid tumors including tumors of the central nervous system. Read more about this study
- Who is it for?
- Ages 2 to 18 years
- Conditions the study is for
- Malignant Solid Tumor - Malignant Nervous System Neoplasm
- What is being tested?
- Cabazitaxel (XRP6258)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 13 sitesin 2 countries
- Study dates
- Feb 2013to Feb 2016
- Phase
- Phase 1/2
- 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 2 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Phase 1 Part (dose escalation): Participants with a histologically confirmed solid tumor including tumors of the central nervous system that was recurrent or refractory and for which no further effective standard treatment was available. All participants must had measurable disease. Participants with diffuse pontine glioma were eligible without a biopsy after evidence of progressive disease post radiation therapy.
- Phase 2 Part (safety and activity): Participants with recurrent or refractory high grade glioma or diffuse intrinsic pontine glioma for whom no further effective therapy was available. All participants must had measurable disease. Participants with diffuse pontine glioma were eligible without a biopsy after evidence of progressive disease post radiation therapy. Participants with a grade III or grade IV glioma must had pathologic confirmation either at the time of initial diagnosis or at the time of recurrence.
- Participants aged ≥2 years and ≤18 years
- Participants met the body surface area (BSA) requirements to be eligible:
- Minimal BSA requirements for a particular dose level;
- During the Phase 1 part participants must had a BSA <2.1 m² at the time of enrollment
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- During the Phase 2 part participants with a BSA ≥2.1 m² were eligible, however the actual dose of cabazitaxel for these participants were adjusted to a maximum dose calculated with (capped at) the BSA of 2.1 m²
- Performance status by:
- Lansky score ≥60 (participants ≤10 years of age)
- Karnofsky score ≥60% (participants >10 years of age) Participants who were unable to walk because of paralysis, but who were mobile in a wheelchair, were considered ambulatory for the purpose of assessing the performance score.
- Participants must had adequate liver, renal and marrow function as defined below:
- Total bilirubin ≤1.0 x the upper limit of normal (ULN) for age
- AST (SGOT) and ALT (SGPT) ≤2.5 x ULN
- Serum creatinine ≤1.5 x ULN for age or creatinine clearance ≥60 mL/min/1.73 m²
- Absolute neutrophil count ≥1.0x10^9 /L
- Platelets ≥75x10^9/L (transfusion independent)
- Hemoglobin ≥8.0 g/dL (could be transfused)
- Female participants of child-bearing potential must had a negative pregnancy test ≤7 days before starting cabazitaxel treatment.
- Male and female participants of reproductive potential must agreed to use adequate contraception prior to study entry, for the duration of study participation and for 6 months following the last dose of cabazitaxel.
- Written informed consent/assent prior to any study-specific procedures. Consent must be obtained from the participant and/or parent(s) or legal guardian(s) and the signature of at least one parent or guardian was required. Investigators also obtained assent of participants according to local, regional or national guidelines.
- Participants must have recovered from the acute toxic effects of all prior therapy to ≤ grade 1 before entering the study.
Who cannot join
- Prior treatment within the following timeframes:
- Systemic anti-cancer treatment within 3 weeks (6 weeks for nitrosourea, mitomycin and monoclonal antibodies including bevacizumab)
- Surgery or smaller field radiation therapy within 4 weeks
- Treatment with an investigational agent within 4 weeks or within 5 half-lives of the agent, whichever was longer Craniospinal or other large field radiation therapy (defined as >25% of bone marrow irradiated) within 6 months prior to the first dose.
- Prior systemic radioisotope therapy (this did not include diagnostic imaging or radioimmunoconjugates lacking myelosuppressive properties) or total body irradiation.
- Prior bone marrow or stem cell transplant
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- Participants with any clinically significant illness that, in the investigator's opinion, could not be adequately controlled with appropriate therapy, would compromise a participant's ability to tolerate cabazitaxel or result in inability to assess toxicity. This included, but was not limited to uncontrolled intercurrent illness including ongoing or active infection, cardiac disease, renal impairment, planned surgery or psychiatric illness/social situations that would limit compliance with study requirements.
- Known human immunodeficiency virus (HIV) infection or acquired immunodeficiency-syndrome (AIDS)-related disease Known history of hepatitis C or known active hepatitis B infection. Pregnant or breast feeding women Treatment with strong inhibitors or strong inducers of CYP3A4 or enzyme inducing anti-epileptic drugs (EIAED) within 14 days prior to first dose of cabazitaxel and for the duration of study. Non-EIAEDs were permitted.
- Known history of hypersensitivity to taxanes or polysorbate 80 or G-CSF. Participation in another interventional clinical trial and/or concurrent treatment with any investigational drug.
- Participants not able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
- The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Trial locations and contacts
13 sites in 2 countries.
13 sites in 2 countries
United States12 sites
Investigational Site Number 840007
Aurora, Colorado, 80045
Investigational Site Number 840010
Baltimore, Maryland, 21287
Investigational Site Number 840002
Boston, Massachusetts, 02115
Investigational Site Number 840012
Chicago, Illinois, 60611
Investigational Site Number 840006
Houston, Texas, 77030
Investigational Site Number 840013
Los Angeles, California, 90027
Investigational Site Number 840003
New York, New York, 10021
Investigational Site Number 840005
Orlando, Florida, 32806
Investigational Site Number 840014
Palo Alto, California
Investigational Site Number 840009
Phoenix, Arizona, 85006
Investigational Site Number 840008
Seattle, Washington, 98105
Investigational Site Number 840011
Washington D.C., District of Columbia, 20010
About this study
Official title: A Phase 1-2 Dose Finding, Safety and Efficacy Study of Cabazitaxel in Pediatric Patients With Refractory Solid Tumors Including Tumors of the Central Nervous System
Primary Objectives:
Phase 1 Part:
Read more
To determine the dose limiting toxicity (DLT) and the maximum tolerated dose (MTD) of cabazitaxel as a single agent in pediatric participants with recurrent or refractory solid tumors including tumors of the central nervous system.
Phase 2 Part:
To determine the objective response rate (complete and partial response) and the duration of response to cabazitaxel as a single agent in participants with recurrent or refractory high grade glioma (HGG) or diffuse intrinsic pontine glioma (DIPG).
Secondary Objectives:
Phase 1 Part:
To characterize the safety and tolerability of cabazitaxel in participants with recurrent or refractory solid tumors including tumors of the central nervous system.
To characterize the pharmacokinetic (PK) profile of cabazitaxel in participants with recurrent or refractory solid tumors including tumors of the central nervous system.
To evaluate preliminary anti-tumor activity that may be associated with cabazitaxel in participants with recurrent or refractory solid tumors including tumors of the central nervous system.
Phase 2 Part:
To characterize the safety and tolerability of cabazitaxel in participants with recurrent or refractory HGG or DIPG.
To estimate progression free survival in participants with recurrent or refractory HGG or DIPG.
To estimate overall survival in participants with recurrent or refractory HGG or DIPG.
To characterize the plasma PK profile of cabazitaxel in participants with recurrent or refractory HGG or DIPG.
Read the detailed description
The study duration will include a period for inclusion of up to 3 weeks and a 3-week treatment cycle(s). The participants may continue treatment until disease progression, unacceptable toxicity or willingness to stop followed by a minimum of 30-day follow-up.
- Being tested
- Cabazitaxel (XRP6258)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cabazitaxel (XRP6258)Drug
Also called Jevtana
Pharmaceutical form: Injection Route of administration: Intravenous
| Study group | Role | What they receive |
|---|---|---|
| Phase 1: Cabazitaxel 20 mg/m^2 | Experimental | Cabazitaxel 20 mg/m^2 intravenous (IV) infusion on Day 1 of each 21-day cycle until disease progression (DP) or discontinuation due to adverse event (AE) or death (from any cause). Receives: Drug: Cabazitaxel (XRP6258) |
| Phase 1: Cabazitaxel 25 mg/m^2 | Experimental | Cabazitaxel 25 mg/m^2 IV infusion on Day 1 of each 21-day cycle until DP or discontinuation due to AE or death (from any cause). Receives: Drug: Cabazitaxel (XRP6258) |
| Phase 1: Cabazitaxel 30 mg/m^2 | Experimental | Cabazitaxel 30 mg/m^2 IV infusion on Day 1 of each 21-day cycle until DP or discontinuation due to AE or death (from any cause). Receives: Drug: Cabazitaxel (XRP6258) |
| Phase 1: Cabazitaxel 35 mg/m^2 | Experimental | Cabazitaxel 35 mg/m^2 IV infusion on Day 1 of each 21-day cycle until DP or discontinuation due to AE or death (from any cause). Receives: Drug: Cabazitaxel (XRP6258) |
| Phase 2: Cabazitaxel 30 mg/m^2 | Experimental | Cabazitaxel at the maximum tolerated dose (MTD) as determined in phase 1 (30 mg/m^2) IV infusion on Day 1 of each 21-day cycle until DP or discontinuation due to AE or death (from any cause). Receives: Drug: Cabazitaxel (XRP6258) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: Maximum Tolerated Dose of Cabazitaxel
MTD was highest dose level of cabazitaxel at which no more than 1 of 6 evaluable participants experienced dose limiting toxicities (DLT). DLT defined as an AE or abnormal laboratory values related to study treatment: hematologic DLTs: any Grade(G)4 hematologic toxicity except neutropenia G4 lasting≤7 days,G3 or 4 febrile neutropenia except G3 or 4 febrile neutropenia in absence of granulocyte-colony stimulating factor prophylaxis, G4 thrombocytopenia; non-hematologic DLTs:any G≥3 non-hematologic toxicity except G3 nausea or G3 or4 vomiting, G3 or4 diarrhea,G3 or4 dehydration,G3 fatigue lasting≤7 days, inadequately treated hypersensitivity reactions, elevated transaminases<10* upper limit of normal of ≤7 days, re-treatment delay of>2 weeks due to delayed recovery from toxicity related to study treatment to baseline G or≤ G1(except for alopecia) and platelet transfusion during Cycle1. Grades based on National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.
Measured: Cycle 1 (21 days)
Phase 2: Percentage of Participants With Objective Response (OR)
OR in participants was defined as the participants with a Complete Response (CR) or Partial Response (PR) after 3 cycles of cabazitaxel treatment and maintained for at least 4 weeks. CR and PR were based on modified response assessment in neuro-oncology (RANO) criteria for participants with CNS tumors. CR was defined as disappearance of all target lesions. PR was defined as ≥50% decrease in the sum of the products of the two perpendicular diameters of target lesions, compared to the baseline measurement.
Measured: Baseline, every 9 weeks until DP or death due to any cause (maximum duration: 12.1 weeks)
Phase 2: Duration of Response (DOR)
DOR defined as time (in days) from date of first response until date of first documented progressive disease (PD) or death (from any cause), whichever came first. If progression or death was not observed, participant was censored at the date of participant's last progression-free tumor assessment prior to study cut-off date. PD as per RANO criteria was defined as ≥ 25% increase in the product of perpendicular diameters of any target lesion, taking as reference the smallest product observed since the start of treatment or the appearance of one or more new lesions, or worsening neurologic status not explained by causes unrelated to tumor progression (example, anticonvulsant or corticosteroid toxicity, electrolyte disturbances, sepsis, hyperglycemia, presumed post-therapy swelling etc.) plus any increase in tumor cross-sectional area (or tumor volume).
Measured: Baseline, every 9 weeks until DP or death due to any cause (maximum duration: 12.1 weeks)
Secondary outcomes (8)
Phase 1 and 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had a causal relationship with the treatment. Treatment emergent adverse events (TEAEs) were defined as AEs that developed or worsened in grade or became serious during the on-treatment period which was defined as the period from the time of first dose of cabazitaxel until 30 days following the last administration of cabazitaxel.
Measured: Baseline up to DP or death due to any cause (maximum duration: 112.1 weeks for Phase 1 and 12.1 weeks for Phase 2)
Phase 1: Number of Participants With Objective Response
OR in participants was defined as the participants with a CR or PR after 3 cycles of cabazitaxel treatment and maintained for at least 4 weeks as assessed by response evaluation criteria in solid tumors (RECIST) version 1.1 and RANO criteria for CNS tumors. For solid tumors, as per RECIST 1.1, CR defined as disappearance of all target and non-target lesions (any pathological lymph nodes, must had reduction in short axis to <10 mm); PR defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. For CNS tumors, as per RANO criteria, CR defined as disappearance of all target and non-target lesions; PR defined as a ≥50% decrease in the sum of the products of the two perpendicular diameters of target lesions, compared to baseline measurement.
Measured: Baseline, every 9 weeks until DP or death due to any cause (maximum duration: 112.1 weeks)
Phase 1 and 2: Pharmacokinetics (PK) Parameter of Cabazitaxel: Area Under the Plasma Concentration (AUC) Versus Time Curve
Blood samples for PK parameters were collected at 5 minutes before end of infusion (EOI), 10 minutes, 30 minutes, 3 hours, 7 hours and 71 hours after the EOI on Day 1 of Cycle 1.
Measured: Day 1 of Cycle 1: 5 minutes before EOI up to 71 hours after the EOI
Phase 1 and 2: PK Parameter of Cabazitaxel: Total Plasma Clearance (CL)
Blood samples for PK parameters were collected at 5 minutes before EOI, 10 minutes, 30 minutes, 3 hours, 7 hours and 71 hours after the EOI on Day 1 of Cycle 1.
Measured: Day 1 of Cycle 1: 5 minutes before EOI up to 71 hours after the EOI
Phase 1 and 2: PK Parameter of Cabazitaxel: Volume of Distribution at Steady State (Vss)
Blood samples for PK parameters were collected at 5 minutes before EOI, 10 minutes, 30 minutes, 3 hours, 7 hours and 71 hours after the EOI on Day 1 of Cycle 1.
Measured: Day 1 of Cycle 1: 5 minutes before EOI up to 71 hours after the EOI
Phase 1 and 2: PK Parameter of Cabazitaxel: Maximum Plasma Concentration Observed (Cmax)
Blood samples for PK parameters were collected at 5 minutes before EOI, 10 minutes, 30 minutes, 3 hours, 7 hours and 71 hours after the EOI on Day 1 of Cycle 1.
Measured: Day 1 of Cycle 1: 5 minutes before EOI up to 71 hours after the EOI
Phase 2: Progression Free Survival (PFS)
The PFS was defined as the time (in months) from the date of first dose administration until the date of first documented PD or death (from any cause), whichever came first. If progression or death was not observed, the participant was censored at the date of the participant's last progression-free tumor assessment prior to the study cut-off date. PD as per RANO criteria was defined as ≥25% increase in the product of perpendicular diameters of any target lesion, taking as reference the smallest product observed since the start of treatment or the appearance of one or more new lesions, or worsening neurologic status not explained by causes unrelated to tumor progression (example, anticonvulsant or corticosteroid toxicity, electrolyte disturbances, sepsis, hyperglycemia, presumed post-therapy swelling etc) plus any increase in tumor cross-sectional area (or tumor volume). The analysis was performed by Kaplan-Meier method.
Measured: Baseline, every 9 weeks until DP or death due to any cause (maximum duration: 12.1 weeks)
Phase 2: Overall Survival (OS)
OS was defined as the time (in months) from the date of first dose administration until the date of death (from any cause). If death was not observed, the participant was censored at the earliest of the last date the participant was known to be alive and the study cut-off date. The analysis was performed by Kaplan-Meier method.
Measured: Baseline up to death or study cut-off (maximum duration: 12.1 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2012 (estimated)
- Study startFeb 2013
- Primary completionJul 2015
- Study completionFeb 2016
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 Malignant Solid Tumor - Malignant Nervous System NeoplasmStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 39 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
- NCT01751308
- Sponsor's protocol ID
- TED12689
- Other IDs
- U1111-1128-5704
- Status last verified
- Jun 2016
- First submitted
- 13 Dec 2012
- Last updated
- 12 Aug 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1-2 Dose Finding, Safety and Efficacy Study of Cabazitaxel in Pediatric Patients With Refractory Solid Tumors Including Tumors of the Central Nervous System
- ClinicalTrials.gov ID
- NCT01751308
- Acronym / sponsor ID
- TED12689
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Study start
- Feb 2013
- Primary completion
- Jul 2015 (actual)
- Study completion
- Feb 2016 (actual)
- First posted
- 17 Dec 2012 (estimated)
- Results
- Posted 12 Aug 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary Objectives:
Phase 1 Part:
To determine the dose limiting toxicity (DLT) and the maximum tolerated dose (MTD) of cabazitaxel as a single agent in pediatric participants with recurrent or refractory solid tumors including tumors of the central nervous system.
Phase 2 Part:
To determine the objective response rate (complete and partial response) and the duration of response to cabazitaxel as a single agent in participants with recurrent or refractory high grade glioma (HGG) or diffuse intrinsic pontine glioma (DIPG).
Secondary Objectives:
Phase 1 Part:
To characterize the safety and tolerability of cabazitaxel in participants with recurrent or refractory solid tumors including tumors of the central nervous system.
To characterize the pharmacokinetic (PK) profile of cabazitaxel in participants with recurrent or refractory solid tumors including tumors of the central nervous system.
To evaluate preliminary anti-tumor activity that may be associated with cabazitaxel in participants with recurrent or refractory solid tumors including tumors of the central nervous system.
Phase 2 Part:
To characterize the safety and tolerability of cabazitaxel in participants with recurrent or refractory HGG or DIPG.
To estimate progression free survival in participants with recurrent or refractory HGG or DIPG.
To estimate overall survival in participants with recurrent or refractory HGG or DIPG.
To characterize the plasma PK profile of cabazitaxel in participants with recurrent or refractory HGG or DIPG.
Detailed description
The study duration will include a period for inclusion of up to 3 weeks and a 3-week treatment cycle(s). The participants may continue treatment until disease progression, unacceptable toxicity or willingness to stop followed by a minimum of 30-day follow-up.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Phase 1: Cabazitaxel 20 mg/m^2 | Experimental | Drug: Cabazitaxel (XRP6258)Cabazitaxel 20 mg/m^2 intravenous (IV) infusion on Day 1 of each 21-day cycle until disease progression (DP) or discontinuation due to adverse event (AE) or death (from any cause). |
| Phase 1: Cabazitaxel 25 mg/m^2 | Experimental | Drug: Cabazitaxel (XRP6258)Cabazitaxel 25 mg/m^2 IV infusion on Day 1 of each 21-day cycle until DP or discontinuation due to AE or death (from any cause). |
| Phase 1: Cabazitaxel 30 mg/m^2 | Experimental | Drug: Cabazitaxel (XRP6258)Cabazitaxel 30 mg/m^2 IV infusion on Day 1 of each 21-day cycle until DP or discontinuation due to AE or death (from any cause). |
| Phase 1: Cabazitaxel 35 mg/m^2 | Experimental | Drug: Cabazitaxel (XRP6258)Cabazitaxel 35 mg/m^2 IV infusion on Day 1 of each 21-day cycle until DP or discontinuation due to AE or death (from any cause). |
| Phase 2: Cabazitaxel 30 mg/m^2 | Experimental | Drug: Cabazitaxel (XRP6258)Cabazitaxel at the maximum tolerated dose (MTD) as determined in phase 1 (30 mg/m^2) IV infusion on Day 1 of each 21-day cycle until DP or discontinuation due to AE or death (from any cause). |
Who may qualify
- Ages
- 2 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (21 listed)
- Phase 1 Part (dose escalation): Participants with a histologically confirmed solid tumor including tumors of the central nervous system that was recurrent or refractory and for which no further effective standard treatment was available. All participants must had measurable disease. Participants with diffuse pontine glioma were eligible without a biopsy after evidence of progressive disease post radiation therapy.
- Phase 2 Part (safety and activity): Participants with recurrent or refractory high grade glioma or diffuse intrinsic pontine glioma for whom no further effective therapy was available. All participants must had measurable disease. Participants with diffuse pontine glioma were eligible without a biopsy after evidence of progressive disease post radiation therapy. Participants with a grade III or grade IV glioma must had pathologic confirmation either at the time of initial diagnosis or at the time of recurrence.
- Participants aged ≥2 years and ≤18 years
- Minimal BSA requirements for a particular dose level;
- During the Phase 1 part participants must had a BSA <2.1 m² at the time of enrollment
Key exclusion criteria (11 listed)
- Systemic anti-cancer treatment within 3 weeks (6 weeks for nitrosourea, mitomycin and monoclonal antibodies including bevacizumab)
- Surgery or smaller field radiation therapy within 4 weeks
- Treatment with an investigational agent within 4 weeks or within 5 half-lives of the agent, whichever was longer Craniospinal or other large field radiation therapy (defined as >25% of bone marrow irradiated) within 6 months prior to the first dose.
- Prior systemic radioisotope therapy (this did not include diagnostic imaging or radioimmunoconjugates lacking myelosuppressive properties) or total body irradiation.
- Prior bone marrow or stem cell transplant
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)Also: JevtanaPharmaceutical form: Injection Route of administration: Intravenous | Drug | Phase 1: Cabazitaxel 20 mg/m^2, Phase 1: Cabazitaxel 25 mg/m^2, Phase 1: Cabazitaxel 30 mg/m^2, Phase 1: Cabazitaxel 35 mg/m^2, Phase 2: Cabazitaxel 30 mg/m^2 |
Primary outcome
Phase 1: Maximum Tolerated Dose of Cabazitaxel
Time frame: Cycle 1 (21 days)
MTD was highest dose level of cabazitaxel at which no more than 1 of 6 evaluable participants experienced dose limiting toxicities (DLT). DLT defined as an AE or abnormal laboratory values related to study treatment: hematologic DLTs: any Grade(G)4 hematologic toxicity except neutropenia G4 lasting≤7 days,G3 or 4 febrile neutropenia except G3 or 4 febrile neutropenia in absence of granulocyte-colony stimulating factor prophylaxis, G4 thrombocytopenia; non-hematologic DLTs:any G≥3 non-hematologic toxicity except G3 nausea or G3 or4 vomiting, G3 or4 diarrhea,G3 or4 dehydration,G3 fatigue lasting≤7 days, inadequately treated hypersensitivity reactions, elevated transaminases<10* upper limit of normal of ≤7 days, re-treatment delay of>2 weeks due to delayed recovery from toxicity related to study treatment to baseline G or≤ G1(except for alopecia) and platelet transfusion during Cycle1. Grades based on National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.
Phase 2: Percentage of Participants With Objective Response (OR)
Time frame: Baseline, every 9 weeks until DP or death due to any cause (maximum duration: 12.1 weeks)
OR in participants was defined as the participants with a Complete Response (CR) or Partial Response (PR) after 3 cycles of cabazitaxel treatment and maintained for at least 4 weeks. CR and PR were based on modified response assessment in neuro-oncology (RANO) criteria for participants with CNS tumors. CR was defined as disappearance of all target lesions. PR was defined as ≥50% decrease in the sum of the products of the two perpendicular diameters of target lesions, compared to the baseline measurement.
Phase 2: Duration of Response (DOR)
Time frame: Baseline, every 9 weeks until DP or death due to any cause (maximum duration: 12.1 weeks)
DOR defined as time (in days) from date of first response until date of first documented progressive disease (PD) or death (from any cause), whichever came first. If progression or death was not observed, participant was censored at the date of participant's last progression-free tumor assessment prior to study cut-off date. PD as per RANO criteria was defined as ≥ 25% increase in the product of perpendicular diameters of any target lesion, taking as reference the smallest product observed since the start of treatment or the appearance of one or more new lesions, or worsening neurologic status not explained by causes unrelated to tumor progression (example, anticonvulsant or corticosteroid toxicity, electrolyte disturbances, sepsis, hyperglycemia, presumed post-therapy swelling etc.) plus any increase in tumor cross-sectional area (or tumor volume).
8 secondary outcomes
Phase 1 and 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Time frame: Baseline up to DP or death due to any cause (maximum duration: 112.1 weeks for Phase 1 and 12.1 weeks for Phase 2)
Phase 1: Number of Participants With Objective Response
Time frame: Baseline, every 9 weeks until DP or death due to any cause (maximum duration: 112.1 weeks)
Phase 1 and 2: Pharmacokinetics (PK) Parameter of Cabazitaxel: Area Under the Plasma Concentration (AUC) Versus Time Curve
Time frame: Day 1 of Cycle 1: 5 minutes before EOI up to 71 hours after the EOI
Phase 1 and 2: PK Parameter of Cabazitaxel: Total Plasma Clearance (CL)
Time frame: Day 1 of Cycle 1: 5 minutes before EOI up to 71 hours after the EOI
Phase 1 and 2: PK Parameter of Cabazitaxel: Volume of Distribution at Steady State (Vss)
Time frame: Day 1 of Cycle 1: 5 minutes before EOI up to 71 hours after the EOI
Phase 1 and 2: PK Parameter of Cabazitaxel: Maximum Plasma Concentration Observed (Cmax)
Time frame: Day 1 of Cycle 1: 5 minutes before EOI up to 71 hours after the EOI
Phase 2: Progression Free Survival (PFS)
Time frame: Baseline, every 9 weeks until DP or death due to any cause (maximum duration: 12.1 weeks)
Phase 2: Overall Survival (OS)
Time frame: Baseline up to death or study cut-off (maximum duration: 12.1 weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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
13 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Cabazitaxel (XRP6258) in people with Malignant Solid Tumor - Malignant Nervous System Neoplasm, run by Sanofi at 13 sites in 2 countries.
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 21 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 12 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States, Canada. 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 combined 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.
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 12 Aug 2016). 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?
Phase 1: Maximum Tolerated Dose of Cabazitaxel (time frame: Cycle 1 (21 days)). The study lists 3 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 12 Aug 2016.