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

NCT01962103 | Completed Phase 1 Results

• 1 other identifier: ABI-007-PST-001
• Study Type: interventional
• Target: 107
• Locations: 7 countries
• Sites: 20

Brief Summary

The purpose of this study is to find the safe dose of nab-paclitaxel in children with solid tumors, and to see if it works to treat these solid tumors in children and young adults (in Phase 1 ≤ 18 years old and in Phase 2 ≤ 24 years old). After the final dose has been chosen, patients will be enrolled according to the specific solid tumor type, (neuroblastoma, rhabdomyosarcoma, or Ewing's sarcoma), to see how nab-paclitaxel works in treating these tumors.

Conditions

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

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

Outcome Measures

Primary Outcomes (3)

• 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.

  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)

  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)

  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 Outcomes (21)

• Phase 1: ORR

  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)

  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

  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)

  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

  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.)

Study Arms (10)

nab-paclitaxel

EXPERIMENTAL

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

Drug: nab-paclitaxel

Phase 1: Nab-Paclitaxel 120 mg/m^2

EXPERIMENTAL

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

Phase 1: Nab-Paclitaxel 150 mg/m^2

EXPERIMENTAL

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

Phase 1: Nab-Paclitaxel 180 mg/m^2

EXPERIMENTAL

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

Phase 1: Nab-Paclitaxel 210 mg/m^2

EXPERIMENTAL

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

Phase 1: Nab-Paclitaxel 240 mg/m^2

EXPERIMENTAL

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

Phase 1: Nab-Paclitaxel 270 mg/m^2

EXPERIMENTAL

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

Phase 2: Ewing's Sarcoma

EXPERIMENTAL

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

Phase 2: Neuroblastoma

EXPERIMENTAL

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

Phase 2: Rhabdomyosarcoma

EXPERIMENTAL

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

Interventions

nab-paclitaxel DRUG

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

Also known as: Abraxane

nab-paclitaxel

Eligibility Criteria

• Age: 6 Months - 24 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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
• 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

You may not qualify if:

• The presence of any of the following will exclude a patient from enrollment:
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• 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.
• 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.

Sponsors & Collaborators

• Celgene: lead

Study Sites (20)

Phoenix Childrens Hospital

Phoenix, Arizona, 85016, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Institute for Pediatric Hematology - Oncology, Leon Berard Cancer Center

Lyon, 69008, France

Location

Hopital d'Enfants, CHU Nancy

Nancy, 54000, France

Location

Institut Curie

Paris, 75005, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Azienda Ospedaliera Universitaria Meyer

Florence, 50139, Italy

Location

Children's Hospital Largo

Genova, 16147, Italy

Location

Istituto Nazionale Tumori

Milan, Italy

Location

Clinica di Oncoematologia

Padua, 35128, Italy

Location

Policlinico Agostino Gemelli

Rome, 00168, Italy

Location

l'Azienda Ospedaliera Regina Margherita - Sant Anna

Torino, 10126, Italy

Location

Hospital Universitario Vall D Hebron

Barcelona, 8035, Spain

Location

Hospital Sant Joan de Deu

Barcelona, 8950, Spain

Location

Spanish National Cancer Research Centre

Madrid, 28029, Spain

Location

Hospital Universitario Virgen Del Rocio

Seville, 41013, Spain

Location

Unidad de Oncologia Pediatrica, Hospital Universitario la Fe

Valencia, 46026, Spain

Location

Universitäts-Kinderklinik

Zurich, 8032, Switzerland

Location

Royal Marsden Hospital

Sutton, SM2 5PT, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 29936064 BACKGROUND

• 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.

  PMID: 32554315 DERIVED

• 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.

  PMID: 31401903 DERIVED

MeSH Terms

Conditions

Neuroblastoma; Rhabdomyosarcoma; Sarcoma, Ewing; Sarcoma; Melanoma; Neoplasms; Osteosarcoma; Histiocytoma; Fibrosarcoma; Dermatofibrosarcoma

Interventions

130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Myosarcoma; Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Neoplasms, Fibrous Tissue

Intervention Hierarchy (Ancestors)

Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Anne McClain, Senior Manager
• Organization: Celgene Corporation

ClinicalTrialDisclosure@Celgene.com

888-260-1599

Study Officials

• Ileana Elias, M.D.

  Celgene Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2013
• First Posted: October 14, 2013
• Study Start: December 4, 2013
• Primary Completion: December 5, 2017
• Study Completion: November 6, 2018
• Last Updated: December 27, 2019
• Results First Posted: December 27, 2018

Record last verified: 2019-12

Locations

FR (4); ES (5); GB (1); CA (1); IT (6); CH (1); US (2)