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Study to Find a Safe Dose and Show Early Clinical Activity of Weekly Nab-paclitaxel in Pediatric Patients With Recurrent/ Refractory Solid Tumors

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ClinicalTrials.gov Identifier: NCT01962103
Recruitment Status : Completed
First Posted : October 14, 2013
Results First Posted : December 27, 2018
Last Update Posted : December 27, 2019
Sponsor:
Information provided by (Responsible Party):
Celgene

Tracking Information
First Submitted Date  ICMJE September 27, 2013
First Posted Date  ICMJE October 14, 2013
Results First Submitted Date  ICMJE December 5, 2018
Results First Posted Date  ICMJE December 27, 2018
Last Update Posted Date December 27, 2019
Actual Study Start Date  ICMJE December 4, 2013
Actual Primary Completion Date December 5, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 5, 2018)
  • Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) [ Time Frame: DLT assessment period: For participants > 10 kg: the first 28-day cycle including Cycle 2 Day 1 predose evaluations; for participants ≤ 10 kg: the first two 28-day cycles including Cycle 3 Day 1 predose evaluations ]
    A DLT was defined as investigational product (IP)-related adverse events occurring during the DLT assessment period that led to treatment discontinuation or met one of the following criteria: - Common Terminology Criteria for Adverse Events (CTCAE) Grade (Gr) 3 or 4 nonhematologic toxicity (excluding transient transaminitis) - CTCAE Gr 3 or 4 nausea or vomiting that persisted > 5 days despite maximal anti-emetic treatment - CTCAE Gr 4 thrombocytopenia or anemia that persisted > 7 days or required transfusion > 7 days - CTCAE Gr 3 thrombocytopenia with bleeding - CTCAE Gr 4 uncomplicated neutropenia lasting > 7 days - Febrile neutropenia with confirmed bacterial infection - CTCAE Gr 3 hematologic toxicity requiring treatment (tx) delay > 21 days. Use of "..." in the table rows signifies the continuation of row title per the above list.
  • Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Median treatment duration in Phase 1 was 7.0 weeks, with minimum and maximum duration of 1 and 49 weeks, respectively. Participants were followed for 28 days after discontinuing treatment for safety and monitoring of AEs. ]
    An adverse event (AE) was defined as any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. A serious AE (SAE) is any AE occurring at any dose that: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. TEAEs were defined as AEs that began or worsened in severity on or after the date of the first dose of study drug and within 28 days of the date of the last dose of study drug. The severity of an AE was graded according to the CTCAE, Version 4.0.
  • Phase 2: Overall Response Rate (ORR) [ Time Frame: Median treatment duration in Phase 2 per group: Ewings Sarcoma = 14 weeks (3-31), Neuroblastoma = 7 weeks (3-23), Rhabdomyosarcoma = 5 weeks (1-13). ]
    Overall response rate was defined as the percentage of participants who achieved a complete response (CR; disappearance of all target lesions) or partial response (PR; at least a 30% decrease in the sum of diameters of target lesions) confirmed no less than 4 weeks after the criteria for response were first met using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 guidelines. (For Phase 2 neuroblastoma participants who had both RECIST and Curie Score tumor evaluations, both tumor response results were considered and an overall response was derived.) Confidence interval was obtained using the Clopper-Pearson method.
Original Primary Outcome Measures  ICMJE
 (submitted: October 10, 2013)
  • Incidence of Dose Limiting Toxicities (DLT) (Phase 1) [ Time Frame: Approximately 98 days ]
    Number of patients with a DLT
  • Incidence of adverse events (Phase 1) [ Time Frame: Up to 2 years ]
    Number of patients with adverse events
  • Overall response rate (ORR) (Phase 2) [ Time Frame: Up to 1 year ]
    Number of patients with Complete response (CR) or partial response (PR) based on investigator assessment of response using RECIST 1.1 guidelines
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 23, 2019)
  • Phase 1: ORR [ Time Frame: Median treatment duration in Phase 1 was 7.0 weeks, with minimum and maximum duration of 1 and 49 weeks, respectively. ]
    Overall response rate was defined as the percentage of participants who achieved a complete response (CR; disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions) confirmed no less than 4 weeks after the criteria for response were first met) using RECIST version 1.1 guidelines over the total number of participants available for the analysis. Confidence interval was obtained using the Clopper-Pearson method.
  • Phase 1: Maximum Observed Concentration of Paclitaxel in Blood Plasma (Cmax) [ Time Frame: Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.) ]
  • Phase 1: Cmax - Dose-Normalized [ Time Frame: Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.) ]
  • Phase 1: Area Under the Plasma Concentration-Time Curve (AUC) [ Time Frame: Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.) ]
    Measurements include: AUC from time zero to the last measurable concentration (AUCt), AUC from time zero to 24 hours (AUC24), and AUC from time zero to infinity (AUCinf).
  • Phase 1: AUC - Dose-Normalized [ Time Frame: Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.) ]
    Measurements include: AUC24 and AUCinf.
  • Phase 1: Clearance (CL) [ Time Frame: Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.) ]
    Measurement of renal clearance from the body.
  • Phase 1: CL - Body Surface Area (BSA)-Normalized [ Time Frame: Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.) ]
    Measurement of renal clearance from the body.
  • Phase 1: Volume of Distribution (Vss) [ Time Frame: Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.) ]
  • Phase 1: Vss - BSA-Normalized [ Time Frame: Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.) ]
  • Phase 1 and 2 Population PK: Volume of Distribution of the Central Compartment (V1) [ Time Frame: Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.) ]
    Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for V1 was 0.888.
  • Phase 1 and 2 Population PK: Maximum Elimination Rate From the Central Compartment (VMEL) [ Time Frame: Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.) ]
    Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for VMEL was 1.12.
  • Phase 1 and 2 Population PK: Concentration in the Central Compartment at 50% of VMEL (KMEL) [ Time Frame: Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.) ]
    Population PK analysis was performed using nonlinear mixed effect modeling.
  • Phase 1 and 2 Population PK: Intercompartmental CL Between the Central Compartment and the First Peripheral Compartment (Q2) [ Time Frame: Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.) ]
    Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for Q2 was 1.12.
  • Phase 1 and 2 Population PK: Intercompartmental CL Between the Central Compartment and the Second Peripheral Compartment (Q3) [ Time Frame: Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.) ]
    Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for Q3 was 1.12.
  • Phase 1 and 2 Population PK: Volume of Distribution of the First Peripheral Compartment (V2) [ Time Frame: Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.) ]
    Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for V2 was 0.888.
  • Phase 1 and 2 Population PK: Volume of Distribution of the Second Peripheral Compartment (V3) [ Time Frame: Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.) ]
    Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for V3 was 0.888.
  • Phase 2: Duration of Response (DOR) [ Time Frame: Median treatment duration in Phase 2 per group: Ewings Sarcoma = 14 weeks (3-31), Neuroblastoma = 7 weeks (3-23), Rhabdomyosarcoma = 5 weeks (1-13). Participants were followed until disease progression (if applicable) up to a maximum of 100.3 weeks. ]
    Duration of response was defined as the time from the date of the first response (CR/PR, using RECIST version 1.1 guidelines) to disease progression for participants with a confirmed CR or PR. Participants who did not have disease progression or had not died were censored at the time of their last disease assessment or at time of start of new anticancer therapy, whichever occurred first. (For Phase 2 neuroblastoma patients who had both RECIST version 1.1 and Curie Score tumor evaluations, both tumor responses results were considered and an overall response was derived.)
  • Phase 2: Disease Control Rate (DCR) [ Time Frame: Median treatment duration in Phase 2 per group: Ewings Sarcoma = 14 weeks (3-31), Neuroblastoma = 7 weeks (3-23), Rhabdomyosarcoma = 5 weeks (1-13). ]
    Disease control rate was defined as the percentage of participants who achieved either a stable disease maintained for ≥ 16 weeks or confirmed CR (confirmed no less than 4 weeks after criteria for response were first met) or confirmed PR (confirmed no less than 4 weeks after criteria for response were first met) over the total number of participants available for the analysis. Confidence interval was obtained using the Clopper-Pearson method.
  • Phase 2: Progression-Free Survival (PFS) [ Time Frame: Median treatment duration in Phase 2 per group: Ewings Sarcoma = 14 weeks (3-31), Neuroblastoma = 7 weeks (3-23), Rhabdomyosarcoma = 5 weeks (1-13). Participants were followed until disease progression (if applicable) up to a maximum of 100.3 weeks. ]
    PFS was defined as the time from the first dose date to the start of disease progression or participant death (any cause), whichever occurred first. Disease progression was classed as either a disease progression observed as a response assessment, or a disease progression or symptomatic deterioration at treatment/study discontinuation. Participants who did not have disease progression or had not died were censored at the last known time that the participant was progression free. Disease progression was considered according to RECIST version 1.1 for Phase 2 Ewing's sarcoma and rhabdomyosarcoma participants. (For Phase 2 neuroblastoma participants who had both RECIST 1.1 and Curie score tumor evaluations, both tumor responses results were considered and an overall response was derived.) Median PFS time was estimated through Kaplan-Meier methods. 95% confidence interval about the median time to PFS event was obtained using Greenwood's method.
  • Phase 2: Kaplan-Meier Estimate of Overall Survival Rate at 1 Year [ Time Frame: 1 year ]
    Overall survival was defined as the time from the first dose date to date of death (any cause). Participants who were alive were censored at the last known time that the participant was alive.
  • Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Median treatment duration in Phase 2 per group: Ewings Sarcoma = 14 weeks (3-31), Neuroblastoma = 7 weeks (3-23), Rhabdomyosarcoma = 5 weeks (1-13). Participants were followed for 28 days after discontinuing treatment for safety and monitoring of AEs. ]
    An AE was defined as any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. A SAE is any AE occurring at any dose that: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. TEAEs were defined as AEs that began or worsened in severity on or after the date of the first dose of study drug and within 28 days of the date of the last dose of study drug. The severity of the AEs was graded according to the Common Terminology Criteria for Adverse Events, Version 4.0. Participants were followed for 28 days after discontinuing treatment for safety and monitoring of AEs.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 10, 2013)
  • Pharmacokinetics (PK) - Cmax (Phase 1) [ Time Frame: Days 1 through 4 ]
    Maximum observed concentration in blood plasma
  • Pharmacokinetics (PK) - AUC (Phase 1) [ Time Frame: Days 1 through 4 ]
    Area under the plasma concentration-time curve
  • Pharmacokinetics (PK) - Clearance (Phase 1) [ Time Frame: Days 1 through 4 ]
    Measurement of renal clearance from the body
  • Pharmacokinetics (PK) - Vss (Phase 1) [ Time Frame: Days 1 through 4 ]
    Volume of distribution
  • Overall Response Rate (ORR) (Phase 1) [ Time Frame: Up to 1 year ]
    Number of patients with complete response (CR) or partial response (PR) based on investigator assessment of response using RECIST 1.1 guidelines
  • Duration of Response (DOR) [ Time Frame: Up to 2 years ]
    Time from complete response (CR) or partial response (PR) [whichever is first recorded] until the date that progression-free survival event is documented
  • Disease Control Rate (DCR) [ Time Frame: Up to 2 years ]
    The percentage of patients with a confirmed objective CR or PR, or stable disease for at least 16 weeks
  • Progression-free survival (PFS) [ Time Frame: Up to 2 years ]
    Time from the start of treatment until the first progression or death by any cause, according to RECIST 1.1 guidelines
  • 1-year survival [ Time Frame: Up to approximately 2 years ]
    Time from the start of treatment until death by any cause
  • Safety [ Time Frame: Up to 2 years ]
    Number of participants with adverse events
  • Pharmacokinetics (PK) -Cmax (Phase 2) [ Time Frame: Days 1 through 4 ]
    Maximum observed concentration in blood
  • Pharmacokinetics (PK) - AUC (Phase 2) [ Time Frame: Days 1 through 4 ]
    Area under the plasma concentration-time curve
  • Pharmacokinetics (PK) - Clearance (Phase 2) [ Time Frame: Days 1 through 4 ]
    Measurement of renal clearance from the body
  • Pharmacokinetics (PK) - Vss (Phase 2) [ Time Frame: Days 1 through 4 ]
    Volume of distribution from both Phase 1 and Phase 2
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Find a Safe Dose and Show Early Clinical Activity of Weekly Nab-paclitaxel in Pediatric Patients With Recurrent/ Refractory Solid Tumors
Official Title  ICMJE A Phase 1/2, Multicenter, Open-label, Dose-finding Study to Assess the Safety, Tolerability, and Preliminary Efficacy of Weekly Nab-paclitaxel in Pediatric Patients With Recurrent or Refractory Solid Tumors.
Brief Summary The purpose of this study is to find the safe dose of nab-paclitaxel in children with solid tumors, and to see if it works to treat these solid tumors in children and young adults (in Phase 1 ≤ 18 years old and in Phase 2 ≤ 24 years old). After the final dose has been chosen, patients will be enrolled according to the specific solid tumor type, (neuroblastoma, rhabdomyosarcoma, or Ewing's sarcoma), to see how nab-paclitaxel works in treating these tumors.
Detailed Description

ABI-007-PST-001 is a Phase 1/2, multicenter, open-label, dose-finding study to assess the safety , tolerability, and preliminary efficacy of weekly nab-paclitaxel in pediatric patients with recurrent or refractory solid tumors (excluding brain tumors). The Phase 1 portion of the study, with a dose escalation design, ended and the recommended Phase 2 dose (RP2D) was determined as 240 mg/m^2 intravenously (IV) in patients weighing > 10 kg and 11.5 mg/kg in patients weighing ≤ 10 kg, on Days 1, 8 and 15 of a 28-day cycle. The Phase 2 portion of the study will enroll additional patients at the RP2D into 1 of 3 solid tumor groups [neuroblastomas, rhabdomyosarcomas, Ewing's sarcomas]. Both phases of the study are open-label and conducted at multiple centers.

The Phase 2 is using a Simon 2-stage design to monitor patient enrollment for each group separately. The rhabdomyosarcoma group, neuroblastoma or Ewing's sarcoma groups did not reach the expected number of 2 responders out of 14 efficacy eligible patients. Consequently, the groups were stopped.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Neuroblastoma
  • Rhabdomyosarcoma
  • Ewing's Sarcoma
  • Ewing's Tumor
  • Sarcoma, Ewing's
  • Sarcomas, Epitheliod
  • Sarcoma, Soft Tissue
  • Sarcoma, Spindle Cell
  • Melanoma
  • Malignant Melanoma
  • Clinical Oncology
  • Oncology, Medical
  • Pediatrics, Osteosarcoma
  • Osteogenic Sarcoma
  • Osteosarcoma Tumor
  • Sarcoma, Osteogenic
  • Tumors
  • Cancer
  • Neoplasia
  • Neoplasm
  • Histiocytoma
  • Fibrosarcoma
  • Dermatofibrosarcoma
Intervention  ICMJE
  • Drug: nab-paclitaxel
    nab-paclitaxel 120-270 mg/m2 IV on Days 1, 8 and 15 of a 28-day cycle
    Other Name: Abraxane
  • Drug: nab-paclitaxel
    IV infusion
    Other Name: Abraxane
Study Arms  ICMJE
  • Experimental: nab-paclitaxel
    nab-paclitaxel 100-240 mg/m2 IV on Days 1, 8 and 15 of a 28-day cycle.
    Intervention: Drug: nab-paclitaxel
  • Experimental: Phase 1: Nab-Paclitaxel 120 mg/m^2
    nab-paclitaxel 120 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.
    Intervention: Drug: nab-paclitaxel
  • Experimental: Phase 1: Nab-Paclitaxel 150 mg/m^2
    nab-paclitaxel 150 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.
    Intervention: Drug: nab-paclitaxel
  • Experimental: Phase 1: Nab-Paclitaxel 180 mg/m^2
    nab-paclitaxel 180 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.
    Intervention: Drug: nab-paclitaxel
  • Experimental: Phase 1: Nab-Paclitaxel 210 mg/m^2
    nab-paclitaxel 210 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.
    Intervention: Drug: nab-paclitaxel
  • Experimental: Phase 1: Nab-Paclitaxel 240 mg/m^2
    nab-paclitaxel 240 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.
    Intervention: Drug: nab-paclitaxel
  • Experimental: Phase 1: Nab-Paclitaxel 270 mg/m^2
    nab-paclitaxel 270 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.
    Intervention: Drug: nab-paclitaxel
  • Experimental: Phase 2: Ewing's Sarcoma
    Participants with Ewing's sarcoma: nab-paclitaxel at the RP2D (240 mg/m^2 in participants weighing > 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity.
    Intervention: Drug: nab-paclitaxel
  • Experimental: Phase 2: Neuroblastoma
    Participants with neuroblastoma: nab-paclitaxel at the RP2D (240 mg/m^2 in participants weighing > 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity.
    Intervention: Drug: nab-paclitaxel
  • Experimental: Phase 2: Rhabdomyosarcoma
    Participants with rhabdomyosarcoma: nab-paclitaxel at the RP2D (240 mg/m^2 in participants weighing > 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity.
    Intervention: Drug: nab-paclitaxel
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 23, 2017)
107
Original Estimated Enrollment  ICMJE
 (submitted: October 10, 2013)
105
Actual Study Completion Date  ICMJE November 6, 2018
Actual Primary Completion Date December 5, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients must meet all of the following criteria to be enrolled in the study:

    1. Patient has a confirmed solid tumor diagnosis according to the

      following:

      1. Phase 1: patient has a recurrent or refractory solid tumor that has

        progressed or did not respond to standard therapy, or for which no

        standard anticancer therapy exists

      2. Phase 2: patient has radiologically documented measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (for neuroblastoma, evaluable disease by 123^I-metaiodobenzylguanidine [MIBG]/Curie score is also acceptable) in 1 of the following tumor types and has failed up to 3 lines of treatment: Group 1: neuroblastoma, Group 2: rhabdomyosarcoma; Group 3: Ewing's sarcoma.
    2. The patient has a Lansky/Karnofsky performance status score of ≥ 70%.
    3. The patient has adequate serum chemistry levels, evidenced by the

      following laboratory values

      1. aspartate aminotransferase (AST)/serum glutamic-oxaloacetric

        transaminase (SGOT), alanine aminotransferase (ALT)/serum glutamic

        pyruvate transaminase (SGPT) ≤ 2.5 × upper limit of normal range (ULN)

      2. Total bilirubin ≤ 1.5 × ULN
      3. Creatinine ≤ 1.5 × ULN
    4. The patient has adequate bone marrow function, evidenced by the

      following:

      1. Absolute neutrophil count ≥ 1.0 × 10^9 cells/L
      2. Platelets ≥ 80 × 10^9 cells/L (transfusion independent, defined as not

        receiving platelet transfusions within 7 days prior to laboratory sample). In the phase 2 portion, for patients with known bone marrow involvement, platelets ≥ 50 × 10^9 cells/L

      3. Hemoglobin ≥ 8 g/dL (transfusion is permitted to fulfill this criterion).
    5. The patient (when applicable) or patient's parent(s) or legal guardian(s)

      understand(s) and voluntarily signed an informed consent document prior

      to any study-related assessments/procedures being conducted. Where

      locally applicable, the patient also understands and voluntarily provides

      his/her assent prior to any study-related assessments/procedures being

      conducted.

    6. Male patients of childbearing potential must use a condom during

      sexual intercourse and shall not father a child during the study and for 6 months after the last dose of study medication.

    7. Female patients of childbearing potential [defined as all female

      patients ≥ 12 years old or who have reached menarche, whichever occurs

      first] must have both of the following:

      a. Agree to the use of two physician-approved contraceptive methods

      simultaneously or practice complete abstinence while on study medication or for a longer period if required by regulations.

      i. True abstinence: When this is in line with the preferred and usual

      lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation,

      symptothermal, postovulation methods) and withdrawal are not

      acceptable methods of contraception.

      ii. Acceptable contraceptive methods include: oral, injectable, or

      implantable hormonal contraceptive; tubal ligation; intra-uterine device;

      barrier contraceptive with spermicide; or vasectomized partner) including

      at least one barrier method.

      b. Have negative serum pregnancy test result at screening confirmed by

      negative urine pregnancy dipstick within 72 hours prior to first dose of

      investigational product (if serum test occurred > 72 hours from first

      dose); pregnancy test with sensitivity of at least 25 mIU/mL.

      Exclusion Criteria:

      • The presence of any of the following will exclude a patient from enrollment:
    1. The patient has a primary brain tumor(s) or brain metastasis (unless metastasis is treated and stable for > 28 days). In patients who are symptomatic, a brain scan is required to exclude metastasis.
    2. The patient has received therapeutic dose chemotherapy or radiotherapy ≤ 21 days prior to start of investigational product.
    3. The patient has received maintenance dose chemotherapy (e.g., low dose cyclophosphamide) ≤ 7 days from the first dose of investigational product.
    4. The patient has received any investigational therapy ≤ 28 days prior to start of investigational product. Investigational therapy is defined as any medicinal product that is not approved in the country of treatment for any indication, adult or pediatric.
    5. The patient has received any biological therapy ≤ 7 days prior to the start of investigational product, or monoclonal antibody ≤ 3 half-lives or 28 days, whichever is shorter, prior to the first dose of investigational product.
    6. The patient has received any hematopoietic stem cell transplantation (HSCT) ≤ 3 months prior to start of investigational product.
    7. The patient has received allogeneic hematopoietic stem cell transplantation (HSCT) ≤ 3 months or autologous HSCT ≤ 21 days prior to start of investigational product.
    8. The patient has not recovered from the acute toxic effects of prior chemotherapy, radiation, or major surgery/significant trauma.
    9. The patient has had minor surgery ≤ 7 days from the start of study treatment (excluding the placement of central/peripheral lines, skin biopsy).
    10. The patient has a known history of stroke, myocardial infarction, peripheral vascular disease, or recent (within 3 months) uncontrolled deep venous thrombosis.
    11. The patient has a known history or current diagnosis of human immunodeficiency virus (HIV) infection, regardless of treatment status.
    12. The patient has an uncontrolled intercurrent illness including but not limited to ongoing or active infection requiring antibiotic, antifungal, or antiviral therapy, symptomatic heart failure, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
    13. The patient has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from participating in the study.
    14. The patient has any condition, including the presence of laboratory abnormalities, that places the patient at unacceptable risk if he/she were to participate in the study.
    15. The patient has any condition that confounds the ability to interpret data from the study.
    16. The patient or parent(s)/guardian(s) is/are unable to comply with the study visit schedule and other protocol requirements, in the opinion of the investigator.
    17. The patient has ≥ Grade 2 peripheral neuropathy by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) at screening.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Months to 24 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   France,   Italy,   Spain,   Switzerland,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01962103
Other Study ID Numbers  ICMJE ABI-007-PST-001
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Celgene
Study Sponsor  ICMJE Celgene
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Ileana Elias, M.D. Celgene Corporation
PRS Account Celgene
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP