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NeuroblastomaPhase 1/2NCT01962103

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

A Phase 1/2 study testing nab-paclitaxel in people with Neuroblastoma and Rhabdomyosarcoma, run by Celgene at 20 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 6 months to 24 years
Conditions the study is for
Neuroblastoma, Rhabdomyosarcoma, Ewing's Sarcoma
What is being tested?
nab-paclitaxel
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
107 participants
Where
20 sitesin 7 countries
Study dates
4 Dec 2013to 6 Nov 2018
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 6 months to 24 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Patients must meet all of the following criteria to be enrolled in the study:
  • Patient has a confirmed solid tumor diagnosis according to the
  • following:
  • 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
Show all 46Show fewer
  • 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.
  • The patient has a Lansky/Karnofsky performance status score of ≥ 70%.
  • The patient has adequate serum chemistry levels, evidenced by the
  • following laboratory values
  • aspartate aminotransferase (AST)/serum glutamic-oxaloacetric
  • transaminase (SGOT), alanine aminotransferase (ALT)/serum glutamic
  • pyruvate transaminase (SGPT) ≤ 2.5 × upper limit of normal range (ULN)
  • Total bilirubin ≤ 1.5 × ULN
  • Creatinine ≤ 1.5 × ULN
  • The patient has adequate bone marrow function, evidenced by the
  • following:
  • Absolute neutrophil count ≥ 1.0 × 10^9 cells/L
  • 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
  • Hemoglobin ≥ 8 g/dL (transfusion is permitted to fulfill this criterion).
  • 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.
  • 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.
  • 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:
  • 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.
  • 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.
  • 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.
  • 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.

Who cannot join

  • The presence of any of the following will exclude a patient from enrollment:
  • <!-- -->
  • 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.
  • The patient has received therapeutic dose chemotherapy or radiotherapy ≤ 21 days prior to start of investigational product.
  • The patient has received maintenance dose chemotherapy (e.g., low dose cyclophosphamide) ≤ 7 days from the first dose of investigational product.
  • 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.
Show all 19Show fewer
  • 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.
  • The patient has received any hematopoietic stem cell transplantation (HSCT) ≤ 3 months prior to start of investigational product.
  • The patient has received allogeneic hematopoietic stem cell transplantation (HSCT) ≤ 3 months or autologous HSCT ≤ 21 days prior to start of investigational product.
  • The patient has not recovered from the acute toxic effects of prior chemotherapy, radiation, or major surgery/significant trauma.
  • The patient has had minor surgery ≤ 7 days from the start of study treatment (excluding the placement of central/peripheral lines, skin biopsy).
  • The patient has a known history of stroke, myocardial infarction, peripheral vascular disease, or recent (within 3 months) uncontrolled deep venous thrombosis.
  • The patient has a known history or current diagnosis of human immunodeficiency virus (HIV) infection, regardless of treatment status.
  • 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.
  • The patient has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from participating in the study.
  • 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.
  • The patient has any condition that confounds the ability to interpret data from the study.
  • 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.
  • The patient has ≥ Grade 2 peripheral neuropathy by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) at screening.

Trial locations and contacts

20 sites in 7 countries.

20 sites in 7 countries

Italy6 sites

  • Azienda Ospedaliera Universitaria Meyer

    Florence, 50139

  • Children's Hospital Largo

    Genova, 16147

  • Istituto Nazionale Tumori

    Milan

  • Clinica di Oncoematologia

    Padova, 35128

  • Policlinico Agostino Gemelli

    Rome, 00168

  • l'Azienda Ospedaliera Regina Margherita - Sant Anna

    Torino, 10126

Other trials in Italy

Spain5 sites

  • Hospital Universitario Vall D Hebron

    Barcelona, 8035

  • Hospital Sant Joan de Deu

    Barcelona, 8950

  • Spanish National Cancer Research Centre

    Madrid, 28029

  • Hospital Universitario Virgen Del Rocio

    Seville, 41013

  • Unidad de Oncologia Pediatrica, Hospital Universitario la Fe

    Valencia, 46026

Other trials in Spain

France4 sites

  • Institute for Pediatric Hematology - Oncology, Leon Berard Cancer Center

    Lyon, 69008

  • Hopital d'Enfants, CHU Nancy

    Nancy, 54000

  • Institut Curie

    Paris, 75005

  • Institut Gustave Roussy

    Villejuif, 94805

Other trials in France

United States2 sites

  • Columbia University Medical Center

    New York, New York, 10032

  • Phoenix Childrens Hospital

    Phoenix, Arizona, 85016

Other trials in United States

Canada1 site

  • The Hospital for Sick Children

    Toronto, Ontario, M5G 1X8

Other trials in Canada

Switzerland1 site

  • Universitäts-Kinderklinik

    Zurich, 8032

Other trials in Switzerland

United Kingdom1 site

  • Royal Marsden Hospital

    Sutton, SM2 5PT

Other trials in United Kingdom

About this study

Official title: 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.

Read the 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.

Being tested
nab-paclitaxel
Keywords
Neuroblastoma, Rhabdomyosarcoma, Soft Tissue, Pediatric Oncology, Abraxane, albumin-bound paclitaxel, nab-paclitaxel, ABI-007, taxane, solid tumors
Medical subject headings
Neuroblastoma, Rhabdomyosarcoma, Sarcoma, Ewing, Sarcoma, Melanoma, Neoplasms, Osteosarcoma, Histiocytoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • nab-paclitaxelDrug

    Also called Abraxane

    nab-paclitaxel 120-270 mg/m2 IV on Days 1, 8 and 15 of a 28-day cycle

  • nab-paclitaxelDrug

    Also called Abraxane

    IV infusion

Study groups in NCT01962103
Study groupRoleWhat they receive
nab-paclitaxelExperimentalnab-paclitaxel 100-240 mg/m2 IV on Days 1, 8 and 15 of a 28-day cycle.
Receives: Drug: nab-paclitaxel
Phase 1: Nab-Paclitaxel 120 mg/m^2Experimentalnab-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.
Receives: Drug: nab-paclitaxel
Phase 1: Nab-Paclitaxel 150 mg/m^2Experimentalnab-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.
Receives: Drug: nab-paclitaxel
Phase 1: Nab-Paclitaxel 180 mg/m^2Experimentalnab-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.
Receives: Drug: nab-paclitaxel
Phase 1: Nab-Paclitaxel 210 mg/m^2Experimentalnab-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.
Receives: Drug: nab-paclitaxel
Phase 1: Nab-Paclitaxel 240 mg/m^2Experimentalnab-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.
Receives: Drug: nab-paclitaxel
Phase 1: Nab-Paclitaxel 270 mg/m^2Experimentalnab-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.
Receives: Drug: nab-paclitaxel
Phase 2: Ewing's SarcomaExperimentalParticipants 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.
Receives: Drug: nab-paclitaxel
Phase 2: NeuroblastomaExperimentalParticipants 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.
Receives: Drug: nab-paclitaxel
Phase 2: RhabdomyosarcomaExperimentalParticipants 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.
Receives: Drug: nab-paclitaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs)

    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.

    Measured: 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

  2. Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

    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.

    Measured: 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.

  3. Phase 2: Overall Response Rate (ORR)

    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.

    Measured: 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 outcomes (21)

  1. Phase 1: ORR

    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.

    Measured: Median treatment duration in Phase 1 was 7.0 weeks, with minimum and maximum duration of 1 and 49 weeks, respectively.

  2. Phase 1: Maximum Observed Concentration of Paclitaxel in Blood Plasma (Cmax)

    Measured: 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.)

  3. Phase 1: Cmax - Dose-Normalized

    Measured: 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.)

  4. Phase 1: Area Under the Plasma Concentration-Time Curve (AUC)

    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).

    Measured: 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.)

  5. Phase 1: AUC - Dose-Normalized

    Measurements include: AUC24 and AUCinf.

    Measured: 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.)

  6. Phase 1: Clearance (CL)

    Measurement of renal clearance from the body.

    Measured: 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.)

  7. Phase 1: CL - Body Surface Area (BSA)-Normalized

    Measurement of renal clearance from the body.

    Measured: 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.)

  8. Phase 1: Volume of Distribution (Vss)

    Measured: 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.)

  9. Phase 1: Vss - BSA-Normalized

    Measured: 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.)

  10. Phase 1 and 2 Population PK: Volume of Distribution of the Central Compartment (V1)

    Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for V1 was 0.888.

    Measured: 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.)

  11. Phase 1 and 2 Population PK: Maximum Elimination Rate From the Central Compartment (VMEL)

    Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for VMEL was 1.12.

    Measured: 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.)

  12. Phase 1 and 2 Population PK: Concentration in the Central Compartment at 50% of VMEL (KMEL)

    Population PK analysis was performed using nonlinear mixed effect modeling.

    Measured: 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.)

  13. Phase 1 and 2 Population PK: Intercompartmental CL Between the Central Compartment and the First Peripheral Compartment (Q2)

    Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for Q2 was 1.12.

    Measured: 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.)

  14. Phase 1 and 2 Population PK: Intercompartmental CL Between the Central Compartment and the Second Peripheral Compartment (Q3)

    Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for Q3 was 1.12.

    Measured: 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.)

  15. Phase 1 and 2 Population PK: Volume of Distribution of the First Peripheral Compartment (V2)

    Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for V2 was 0.888.

    Measured: 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.)

  16. Phase 1 and 2 Population PK: Volume of Distribution of the Second Peripheral Compartment (V3)

    Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for V3 was 0.888.

    Measured: 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.)

  17. Phase 2: Duration of Response (DOR)

    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.)

    Measured: 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.

  18. Phase 2: Disease Control Rate (DCR)

    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.

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

  19. Phase 2: Progression-Free Survival (PFS)

    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.

    Measured: 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.

  20. Phase 2: Kaplan-Meier Estimate of Overall Survival Rate at 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.

    Measured: 1 year

  21. Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

    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.

    Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Oct 2013 (estimated)
  2. Study start4 Dec 2013
  3. Primary completion5 Dec 2017
  4. Study completion6 Nov 2018

Resources

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
107 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01962103
Sponsor's protocol ID
ABI-007-PST-001
Status last verified
Dec 2019
First submitted
27 Sep 2013
Last updated
27 Dec 2019
Data monitoring committee
No

Publications

  • Moreno L, Casanova M, Chisholm JC, Berlanga P, Chastagner PB, Baruchel S, Amoroso L, Gallego Melcon S, Gerber NU, Bisogno G, Fagioli F, Geoerger B, Glade Bender JL, Aerts I, Bergeron C, Hingorani P, Elias I, Simcock M, Ferrara S, Le Bruchec Y, Slepetis R, Chen N, Vassal G. Phase I results of a phase I/II study of weekly nab-paclitaxel in paediatric patients with recurrent/refractory solid tumours: A collaboration with innovative therapies for children with cancer. Eur J Cancer. 2018 Sep;100:27-34. doi: 10.1016/j.ejca.2018.05.002. Epub 2018 Jun 21.

    PubMed 29936064

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Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing nab-paclitaxel in people with Neuroblastoma and Rhabdomyosarcoma, run by Celgene at 20 sites in 7 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 46 inclusion and 19 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 27 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in Italy, Spain, France, United States, Canada and 2 more countries. 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 27 Dec 2018). 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: 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). 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?

On the ClinicalTrials.gov record for NCT01962103, which also lists 3 linked publications.

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 27 Dec 2019.

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