Nab-paclitaxel in Combination with Gemcitabine for Pediatric Relapsed and Refractory Solid Tumors

NCT03507491 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: IRB00098777
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 4

Brief Summary

This is a research study for people who have a solid tumor that was not effectively treated by conventional therapy or for which there is no known effective therapy. This is a phase I study of a drug called nab-paclitaxel used together with gemcitabine. Gemcitabine and nab-paclitaxel will be given intravenously, once a week for 3 out of 4 weeks, for a 28-day cycle. The goals of this study are:

• To find the highest dose of nab-paclitaxel that can be safely given in combination with gemcitabine without causing severe side effects
• To learn what kind of side effects nab-paclitaxel given in combination with gemcitabine can cause
• To learn more about the pharmacology (how the body handles the drug) of nab-paclitaxel given in combination with gemcitabine
• To evaluate tumor tissue for levels of certain proteins that may help with predicting who will benefit most from treatment with nab-paclitaxel
• To determine whether nab-paclitaxel given in combination with gemcitabine is a beneficial treatment for relapsed and/or refractory solid tumors

Conditions

Cancer

Keywords

Pediatric; Sarcoma; Neuroblastoma; Ewing sarcoma; Osteosarcoma; Rhabdomyosarcoma; Wilms tumor; Hepatoblastoma; Adolescent and young adult; Germ cell tumor

Outcome Measures

Primary Outcomes (2)

• Maximum dose tolerated of nab-paclitaxel

  The maximum tolerated dose (MTD) of nab-paclitaxel administered intravenously weekly every 3 of 4 weeks in combination with gemcitabine in children with refractory/relapsed non-CNS solid tumors will be determined. The MTD is empirically defined as the highest dose level at which there is no more than one patient experiencing a dose-limiting toxicity (DLT) and the next higher dose level has been determined to be too toxic. The MTD will be determined during Cycle 1 (each cycle is 28 days)

  Up to Day 28

• Toxicity of nab-paclitaxel

  The toxicities of nab-paclitaxel in combination with gemcitabine administered intravenously weekly every 3 of 4 weeks will be determined. All toxicities observed will be summarized in terms of type (organ affected or laboratory determination), severity (by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0), and attribution. Data on toxicities will be collected during the entire time a participant is in the study (up to 24 cycles, each cycle is 28 days).

  Up to 96 weeks

Secondary Outcomes (3)

• Antitumor activity of nab-paclitaxel

  Up to 96 weeks

• Change in secreted protein acidic and rich in cysteine (SPARC) expression

  Up to 96 weeks

• Blood concentrations of paclitaxel

  Up to Day 3

Study Arms (1)

Gemcitabine + Nab-paclitaxel

EXPERIMENTAL

Participants receiving gemcitabine and nab-paclitaxel for refractory and/or relapsed solid tumors of childhood.

Drug: Gemcitabine; Drug: Nab-paclitaxel

Interventions

Gemcitabine DRUG

Gemcitabine will be administered intravenously once weekly over 60 minutes every 3 out of four weeks. The dose of gemcitabine will start at 675 mg/m2/dose. If the MTD has been exceeded at the Dose Level 1, then the subsequent cohort of participants will be treated with gemcitabine at a dose of 500 mg/m2/dose (Dose Level 0).

Also known as: Gemzar

Gemcitabine + Nab-paclitaxel

Nab-paclitaxel DRUG

Nab-Paclitaxel will be administered intravenously over 30 minutes once weekly every 3 out of 4 weeks. Nab-paclitaxel will be administered prior to administration of gemcitabine. The starting dose of nab-paclitaxel will be 180 mg/m2/dose (dose level 1). Dose levels for subsequent groups of subjects are 210 mg/m2/dose (for dose level 2) and 240 mg/m2/dose (for dose level 3).

Also known as: Abraxane

Gemcitabine + Nab-paclitaxel

Eligibility Criteria

• Age: 6 Months - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Subjects must be ≥ than 6 months and ≤ 30 years of age at the time of study enrollment.
• Subjects must have had histologic verification of a malignancy at original diagnosis or relapse.
• All subjects with relapsed or refractory solid tumors are eligible, excluding primary CNS tumors.
• Patients with solid tumors and a history of intraparenchymal CNS disease are eligible if their CNS disease was treated surgically or with radiotherapy and stable with no recurrent lesions for at least 3 months from the start of protocol therapy.
• Newly diagnosed patients with ≤15% chance of cure if given standard-of-care chemotherapy are eligible. (Prognosis to be determined at the discretion of the treating physician.)
• Subjects must have either measurable or evaluable disease.
• Karnofsky ≥ 60 for subjects \> 16 years of age and Lansky ≥ 50 for subjects ≤ 16 years of age. Subjects who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• Subjects must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy.
• At least 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea).
• At least 14 days after the last dose of a long-acting growth factor (e.g. Pegfilgrastim) or 7 days for short acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair.
• At least 7 days after the last dose of a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair.
• ≥ 42 days must have elapsed from last dose of any type of cellular therapy (e.g. modified T cells, natural killer (NK) cells, dendritic cells, etc.)
• ≥ 21 days must have elapsed from the last dose of interleukins, interferon or cytokines (other than Hematopoietic Growth Factors).
• ≥ 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to Grade ≤ 1.
• At least 14 days after local palliative radiation therapy (XRT) (small port); 6 weeks must have elapsed since treatment with therapeutic doses of iodine-131 metaiodobenzylguanidine (131I-MIBG); At least 42 days must have elapsed if other substantial bone marrow (BM) radiation.

You may not qualify if:

• Female patients who are pregnant are ineligible for study. Lactating females are not eligible unless they have agreed not to breastfeed their infants from the time of informed consent through the duration and at least 1 month following the last dose of investigational agent. Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained. Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method from the time of informed consent through the duration and for 1 month following the last dose of investigational agent. The definition of an effective contraceptive method will be at the discretion of the institutional investigator.
• Patients taking any the following concomitant medications are not eligible:
• Subjects who are currently receiving another investigational drug.
• Subjects who are currently receiving other anti-cancer agents.
• Subjects who are receiving cyclosporine, tacrolimus, or other agents to prevent graft-versus-host disease post bone marrow transplant.
• Subjects using medications which interfere with CYP3A4 and CYP2C8 metabolism, which metabolize nab-paclitaxel. Paclitaxel is metabolized by CYP3A4 and CYP2C8, so strong inhibitors or inducers of these enzymes should be avoided.
• Patients with any of the following adverse events at the time of enrollment are not eligible:
• Grade ≥ 2 Motor, sensory or peripheral neuropathy. This does not apply to patients with neuropathic symptoms related to tumor or prior therapy, i.e. surgery or radiation. Patients with mild neuropathy well controlled with medications are eligible.
• Grade ≥3 Hyponatremia (serum Na ≤ 130 mmol/L)
• Subjects who have an uncontrolled infection are not eligible.
• Subjects who have received prior solid organ transplantation are not eligible.
• Subjects who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.

Sponsors & Collaborators

• Emory University: lead
• Celgene Corporation: collaborator

Study Sites (4)

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

Chilldren's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

MeSH Terms

Conditions

Neoplasms; Sarcoma; Neuroblastoma; Sarcoma, Ewing; Osteosarcoma; Rhabdomyosarcoma; Wilms Tumor; Hepatoblastoma; Neoplasms, Germ Cell and Embryonal

Interventions

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

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Myosarcoma; Neoplasms, Muscle Tissue; Neoplasms, Complex and Mixed; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplastic Syndromes, Hereditary; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Thomas Cash, MD, MSc

  Emory University

  STUDY CHAIR

• Jonathan Metts, MD

  Johns Hopkins All Children's Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: March 22, 2018
• First Posted: April 25, 2018
• Study Start: August 27, 2018
• Primary Completion: February 2, 2024
• Study Completion: February 2, 2024
• Last Updated: October 4, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)