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

NCT ID: NCT01962103

Last Updated: 2019-12-27

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

107 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-12-04

Study Completion Date

2018-11-06

Brief Summary

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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

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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.

Conditions

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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

Keywords

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Neuroblastoma Rhabdomyosarcoma Soft Tissue Pediatric Oncology Abraxane albumin-bound paclitaxel nab-paclitaxel ABI-007 taxane solid tumors

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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nab-paclitaxel

nab-paclitaxel 100-240 mg/m2 IV on Days 1, 8 and 15 of a 28-day cycle.

Group Type EXPERIMENTAL

nab-paclitaxel

Intervention Type DRUG

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

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.

Group Type EXPERIMENTAL

nab-paclitaxel

Intervention Type DRUG

IV infusion

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.

Group Type EXPERIMENTAL

nab-paclitaxel

Intervention Type DRUG

IV infusion

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.

Group Type EXPERIMENTAL

nab-paclitaxel

Intervention Type DRUG

IV infusion

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.

Group Type EXPERIMENTAL

nab-paclitaxel

Intervention Type DRUG

IV infusion

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.

Group Type EXPERIMENTAL

nab-paclitaxel

Intervention Type DRUG

IV infusion

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.

Group Type EXPERIMENTAL

nab-paclitaxel

Intervention Type DRUG

IV infusion

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.

Group Type EXPERIMENTAL

nab-paclitaxel

Intervention Type DRUG

IV infusion

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.

Group Type EXPERIMENTAL

nab-paclitaxel

Intervention Type DRUG

IV infusion

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.

Group Type EXPERIMENTAL

nab-paclitaxel

Intervention Type DRUG

IV infusion

Interventions

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nab-paclitaxel

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

Intervention Type DRUG

nab-paclitaxel

IV infusion

Intervention Type DRUG

Other Intervention Names

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Abraxane Abraxane

Eligibility Criteria

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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:

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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.
Minimum Eligible Age

6 Months

Maximum Eligible Age

24 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Celgene

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ileana Elias, M.D.

Role: STUDY_DIRECTOR

Celgene Corporation

Locations

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Phoenix Childrens Hospital

Phoenix, Arizona, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

The Hospital for Sick Children

Toronto, Ontario, Canada

Site Status

Institute for Pediatric Hematology - Oncology, Leon Berard Cancer Center

Lyon, , France

Site Status

Hopital d'Enfants, CHU Nancy

Nancy, , France

Site Status

Institut Curie

Paris, , France

Site Status

Institut Gustave Roussy

Villejuif, , France

Site Status

Azienda Ospedaliera Universitaria Meyer

Florence, , Italy

Site Status

Children's Hospital Largo

Genova, , Italy

Site Status

Istituto Nazionale Tumori

Milan, , Italy

Site Status

Clinica di Oncoematologia

Padua, , Italy

Site Status

Policlinico Agostino Gemelli

Rome, , Italy

Site Status

l'Azienda Ospedaliera Regina Margherita - Sant Anna

Torino, , Italy

Site Status

Hospital Universitario Vall D Hebron

Barcelona, , Spain

Site Status

Hospital Sant Joan de Deu

Barcelona, , Spain

Site Status

Spanish National Cancer Research Centre

Madrid, , Spain

Site Status

Hospital Universitario Virgen Del Rocio

Seville, , Spain

Site Status

Unidad de Oncologia Pediatrica, Hospital Universitario la Fe

Valencia, , Spain

Site Status

Universitäts-Kinderklinik

Zurich, , Switzerland

Site Status

Royal Marsden Hospital

Sutton, , United Kingdom

Site Status

Countries

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United States Canada France Italy Spain Switzerland United Kingdom

References

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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.

Reference Type BACKGROUND
PMID: 29936064 (View on PubMed)

Amoroso L, Castel V, Bisogno G, Casanova M, Marquez-Vega C, Chisholm JC, Doz F, Moreno L, Ruggiero A, Gerber NU, Fagioli F, Hingorani P, Melcon SG, Slepetis R, Chen N, le Bruchec Y, Simcock M, Vassal G. Phase II results from a phase I/II study to assess the safety and efficacy of weekly nab-paclitaxel in paediatric patients with recurrent or refractory solid tumours: A collaboration with the European Innovative Therapies for Children with Cancer Network. Eur J Cancer. 2020 Aug;135:89-97. doi: 10.1016/j.ejca.2020.04.031. Epub 2020 Jun 15.

Reference Type DERIVED
PMID: 32554315 (View on PubMed)

Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14.

Reference Type DERIVED
PMID: 31401903 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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ABI-007-PST-001

Identifier Type: -

Identifier Source: org_study_id