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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2016 by Celgene Corporation
Information provided by (Responsible Party):
Celgene Corporation Identifier:
First received: September 27, 2013
Last updated: April 20, 2016
Last verified: April 2016
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 (≤ 21 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.

Condition Intervention Phase
Ewing's Sarcoma;
Ewing's Tumor;
Sarcoma, Ewing's;
Sarcomas, Epitheliod;
Sarcoma, Soft Tissue;
Sarcoma, Spindle Cell;
Malignant Melanoma;
Clinical Oncology;
Oncology, Medical;
Pediatrics, Osteosarcoma;
Osteogenic Sarcoma;
Osteosarcoma Tumor;
Sarcoma, Osteogenic;
Drug: nab-paclitaxel
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:

Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • Incidence of Dose Limiting Toxicities (DLT) (Phase 1) [ Time Frame: Approximately 98 days ] [ Designated as safety issue: Yes ]
    Number of patients with a DLT

  • Incidence of adverse events (Phase 1) [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
    Number of patients with adverse events

  • Overall response rate (ORR) (Phase 2) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Number of patients with complete response (CR) or partial response (PR) based on investigator assessment of response using RECIST 1.1 criteria. In the neuroblastoma group the ORR will be determined by RECIST and/or the Curie Scale (MIBG response)

Secondary Outcome Measures:
  • Pharmacokinetics (PK) - Cmax (Phase 1) [ Time Frame: Days 1 through 4 ] [ Designated as safety issue: No ]
    Maximum observed concentration in blood plasma

  • Pharmacokinetics (PK) - AUC (Phase 1) [ Time Frame: Days 1 through 4 ] [ Designated as safety issue: No ]
    Area under the plasma concentration-time curve

  • Pharmacokinetics (PK) - Clearance (Phase 1) [ Time Frame: Days 1 through 4 ] [ Designated as safety issue: No ]
    Measurement of renal clearance from the body

  • Pharmacokinetics (PK) - Vss (Phase 1) [ Time Frame: Days 1 through 4 ] [ Designated as safety issue: No ]
    Volume of distribution

  • Overall Response Rate (ORR) (Phase 1) [ Time Frame: Up to 2 year ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 3 years ] [ Designated as safety issue: No ]
    Time from the start of treatment until the first progression or death by any cause, according to RECIST 1.1 guidelines. In the neuroblastoma group the PFS will be determined by RECIST and/or the Curie scale (MIBG response).

  • 1-year survival [ Time Frame: Up to approximately 2 years ] [ Designated as safety issue: No ]
    Time from the start of treatment until death by any cause

  • Safety [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Number of participants with adverse events

  • Pharmacokinetics (PK) -Cmax (Phase 2) [ Time Frame: Days 1 through 4 ] [ Designated as safety issue: No ]
    Maximum observed concentration in blood

  • Pharmacokinetics (PK) - AUC (Phase 2) [ Time Frame: Days 1 through 4 ] [ Designated as safety issue: No ]
    Area under the plasma concentration-time curve

  • Pharmacokinetics (PK) - Clearance (Phase 2) [ Time Frame: Days 1 through 4 ] [ Designated as safety issue: No ]
    Measurement of renal clearance from the body

  • Pharmacokinetics (PK) - Vss (Phase 2) [ Time Frame: Days 1 through 4 ] [ Designated as safety issue: No ]
    Volume of distribution from both Phase 1 and Phase 2

Estimated Enrollment: 134
Study Start Date: December 2013
Estimated Study Completion Date: February 2020
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: nab-paclitaxel
nab-paclitaxel 100-240 mg/m2 IV on Days 1, 8 and 15 of a 28-day cycle.
Drug: nab-paclitaxel
nab-paclitaxel 100-240 mg/m2 IV on Days 1, 8 and 15 of a 28-day cycle
Other Name: Abraxane

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 will be dose escalation design to determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D). The Phase 2 portion of the study will enroll additional patients at the RP2D into one of three solid tumor groups [Neuroblastomas, Rhabdomyosarcomas, Ewing's Sarcomas]. Both phases of the study will be open-label and conducted at multiple centers.

Ages Eligible for Study:   6 Months to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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:

      a. 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 b. Phase 2: patient has radiologically documented measurable disease by RECIST 1.1 (for neuroblastoma, evaluable disease by MIBG/Curie score is also acceptable) in one of the following tumor types and has failed first or second-line treatment or has evidence of refractory disease i. Group 1: neuroblastoma ii. Group 2: rhabdomyosarcoma iii. Group 3: Ewing's sarcoma Phase 1 portion or in preclinical studies

    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 (IP) (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 had major surgery or significant trauma ≤ 14 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01962103

Contact: Associate Director Clinical Trial Disclosure 1-888-260-1599

United States, Arizona
Phoenix Childrens Hospital Recruiting
Phoenix, Arizona, United States, 85016
United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Canada, Ontario
The Hospital for Sick Children Recruiting
Toronto, Ontario, Canada, M5G 1X8
Institute for Pediatric Hemato-Oncology, Leon Berard Cancer Center Recruiting
Lyon, France, 69008
Hopital d'Enfants, CHU Nancy Recruiting
Nancy, France, 54000
Institut Curie Recruiting
Paris, France, 75005
Institut Gustave Roussy Recruiting
Villejuif, France, 94805
Azienda Ospedaliera Universitaria Meyer Not yet recruiting
Firenze, Italy, 50139
Children's Hospital Largo Recruiting
Genova, Italy, 16147
Istituto Nazionale Tumori Recruiting
Milan, Italy
Clinica di Oncoematologia Recruiting
Padova, Italy, 35128
Policlinico Agostino Gemelli Not yet recruiting
Rome, Italy, 00168
l'Azienda Ospedaliera Regina Margherita - Sant Anna Recruiting
Torino, Italy, 10126
Hospital Universitario Vall D`Hebron Recruiting
Barcelona, Spain, 8035
Hospital Sant Joan de Deu Not yet recruiting
Barcelona, Spain, 8950
Spanish National Cancer Research Centre Recruiting
Madrid, Spain, 28029
Hospital Universitario Virgen Del Rocio Not yet recruiting
Sevilla, Spain, 41013
Unidad de Oncologia Pediatrica, Hospital Universitario la Fe Recruiting
Valencia, Spain, 46026
Universitäts-Kinderklinik Recruiting
Zurich, Switzerland, 8032
United Kingdom
Royal Marsden Hospital Recruiting
Sutton, United Kingdom, SM2 5PT
Sponsors and Collaborators
Celgene Corporation
Study Director: Ileana Elias, M.D. Celgene Corporation
  More Information

Responsible Party: Celgene Corporation Identifier: NCT01962103     History of Changes
Other Study ID Numbers: ABI-007-PST-001 
Study First Received: September 27, 2013
Last Updated: April 20, 2016
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
France: Agence Nationale de Sécurité du Medicament et des produits de santé
Italy: The Italian Medicines Agency
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Switzerland: Swissmedic. Swiss Agency for Therapeutic Products
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Celgene Corporation:
Neuroblastoma, Rhabdomyosarcoma, Soft Tissue; Pediatric Oncology, Abraxane, albumin-bound paclitaxel, nab-paclitaxel, ABI-007, taxane, solid tumors

Additional relevant MeSH terms:
Sarcoma, Ewing
Neoplasms by Histologic Type
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms, Fibrous Tissue
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Muscle Tissue
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Neuroectodermal Tumors, Primitive, Peripheral
Neuroendocrine Tumors
Nevi and Melanomas
Albumin-Bound Paclitaxel
Antimitotic Agents
Antineoplastic Agents processed this record on May 30, 2016