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

December 19, 2019 updated by: Celgene

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.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

107

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 1X8
        • The Hospital for Sick Children
  • France
      • Lyon, France, 69008
        • Institute for Pediatric Hematology - Oncology, Leon Berard Cancer Center
      • Nancy, France, 54000
        • Hopital d'Enfants, CHU Nancy
      • Paris, France, 75005
        • Institut Curie
      • Villejuif, France, 94805
        • Institut Gustave Roussy
  • Italy
      • Firenze, Italy, 50139
        • Azienda Ospedaliera Universitaria Meyer
      • Genova, Italy, 16147
        • Children's Hospital Largo
      • Milan, Italy
        • Istituto Nazionale Tumori
      • Padova, Italy, 35128
        • Clinica di Oncoematologia
      • Rome, Italy, 00168
        • Policlinico Agostino Gemelli
      • Torino, Italy, 10126
        • l'Azienda Ospedaliera Regina Margherita - Sant Anna
  • Spain
      • Barcelona, Spain, 8035
        • Hospital Universitario Vall d Hebron
      • Barcelona, Spain, 8950
        • Hospital Sant Joan de Deu
      • Madrid, Spain, 28029
        • Spanish National Cancer Research Centre
      • Sevilla, Spain, 41013
        • Hospital Universitario Virgen del Rocio
      • Valencia, Spain, 46026
        • Unidad de Oncologia Pediatrica, Hospital Universitario la Fe
  • Switzerland
      • Zurich, Switzerland, 8032
        • Universitäts-Kinderklinik
  • United Kingdom
      • Sutton, United Kingdom, SM2 5PT
        • Royal Marsden Hospital
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85016
        • Phoenix Childrens Hospital
    • New York
      • New York, New York, United States, 10032
        • Columbia University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 months to 24 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: nab-paclitaxel
nab-paclitaxel 100-240 mg/m2 IV on Days 1, 8 and 15 of a 28-day cycle.
Drug: nab-paclitaxel
IV infusion
Other Names:
  • Abraxane
Drug: nab-paclitaxel
nab-paclitaxel 120-270 mg/m2 IV on Days 1, 8 and 15 of a 28-day cycle
Other Names:
  • Abraxane
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.
Drug: nab-paclitaxel
IV infusion
Other Names:
  • Abraxane
Drug: nab-paclitaxel
nab-paclitaxel 120-270 mg/m2 IV on Days 1, 8 and 15 of a 28-day cycle
Other Names:
  • Abraxane
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.
Drug: nab-paclitaxel
IV infusion
Other Names:
  • Abraxane
Drug: nab-paclitaxel
nab-paclitaxel 120-270 mg/m2 IV on Days 1, 8 and 15 of a 28-day cycle
Other Names:
  • Abraxane
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.
Drug: nab-paclitaxel
IV infusion
Other Names:
  • Abraxane
Drug: nab-paclitaxel
nab-paclitaxel 120-270 mg/m2 IV on Days 1, 8 and 15 of a 28-day cycle
Other Names:
  • Abraxane
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.
Drug: nab-paclitaxel
IV infusion
Other Names:
  • Abraxane
Drug: nab-paclitaxel
nab-paclitaxel 120-270 mg/m2 IV on Days 1, 8 and 15 of a 28-day cycle
Other Names:
  • Abraxane
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.
Drug: nab-paclitaxel
IV infusion
Other Names:
  • Abraxane
Drug: nab-paclitaxel
nab-paclitaxel 120-270 mg/m2 IV on Days 1, 8 and 15 of a 28-day cycle
Other Names:
  • Abraxane
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.
Drug: nab-paclitaxel
IV infusion
Other Names:
  • Abraxane
Drug: nab-paclitaxel
nab-paclitaxel 120-270 mg/m2 IV on Days 1, 8 and 15 of a 28-day cycle
Other Names:
  • Abraxane
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.
Drug: nab-paclitaxel
IV infusion
Other Names:
  • Abraxane
Drug: nab-paclitaxel
nab-paclitaxel 120-270 mg/m2 IV on Days 1, 8 and 15 of a 28-day cycle
Other Names:
  • Abraxane
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.
Drug: nab-paclitaxel
IV infusion
Other Names:
  • Abraxane
Drug: nab-paclitaxel
nab-paclitaxel 120-270 mg/m2 IV on Days 1, 8 and 15 of a 28-day cycle
Other Names:
  • Abraxane
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.
Drug: nab-paclitaxel
IV infusion
Other Names:
  • Abraxane
Drug: nab-paclitaxel
nab-paclitaxel 120-270 mg/m2 IV on Days 1, 8 and 15 of a 28-day cycle
Other Names:
  • Abraxane

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
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
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.
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.
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.
Median treatment duration in Phase 2 per group: Ewings Sarcoma = 14 weeks (3-31), Neuroblastoma = 7 weeks (3-23), Rhabdomyosarcoma = 5 weeks (1-13).

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Median treatment duration in Phase 1 was 7.0 weeks, with minimum and maximum duration of 1 and 49 weeks, respectively.
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.)
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.)
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).
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: 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.
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: 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.
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: 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.
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: 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.)
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.)
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.
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: 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.
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: 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.
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: 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.
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: 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.
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 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.
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 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.
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 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.)
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.
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.
Median treatment duration in Phase 2 per group: Ewings Sarcoma = 14 weeks (3-31), Neuroblastoma = 7 weeks (3-23), Rhabdomyosarcoma = 5 weeks (1-13).
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.
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.
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.
1 year
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.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Celgene

Investigators

  • Study Director: Ileana Elias, M.D., Celgene Corporation

Publications and helpful links

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General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 4, 2013

Primary Completion (Actual)

December 5, 2017

Study Completion (Actual)

November 6, 2018

Study Registration Dates

First Submitted

September 27, 2013

First Submitted That Met QC Criteria

October 10, 2013

First Posted (Estimate)

October 14, 2013

Study Record Updates

Last Update Posted (Actual)

December 27, 2019

Last Update Submitted That Met QC Criteria

December 19, 2019

Last Verified

December 1, 2019

More Information

Terms related to this study

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Other Study ID Numbers

  • ABI-007-PST-001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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