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
Overview
- Phase
- Phase 1
- Intervention
- Cabazitaxel (XRP6258)
- Conditions
- Malignant Solid Tumor - Malignant Nervous System Neoplasm
- Sponsor
- Sanofi
- Enrollment
- 39
- Locations
- 13
- Primary Endpoint
- Phase 1: Maximum Tolerated Dose of Cabazitaxel
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief 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.
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Phase 1: Cabazitaxel 20 mg/m^2
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).
Intervention: Cabazitaxel (XRP6258)
Phase 1: Cabazitaxel 25 mg/m^2
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).
Intervention: Cabazitaxel (XRP6258)
Phase 1: Cabazitaxel 30 mg/m^2
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).
Intervention: Cabazitaxel (XRP6258)
Phase 1: Cabazitaxel 35 mg/m^2
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).
Intervention: Cabazitaxel (XRP6258)
Phase 2: Cabazitaxel 30 mg/m^2
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).
Intervention: Cabazitaxel (XRP6258)
Outcomes
Primary Outcomes
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).
Secondary Outcomes
- Phase 1: Number of Participants With Objective Response(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(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)(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)(Day 1 of Cycle 1: 5 minutes before EOI up to 71 hours after the EOI)
- Phase 2: Progression Free Survival (PFS)(Baseline, every 9 weeks until DP or death due to any cause (maximum duration: 12.1 weeks))
- Phase 2: Overall Survival (OS)(Baseline up to death or study cut-off (maximum duration: 12.1 weeks))
- Phase 1 and 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs)(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 and 2: PK Parameter of Cabazitaxel: Volume of Distribution at Steady State (Vss)(Day 1 of Cycle 1: 5 minutes before EOI up to 71 hours after the EOI)