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Nab-paclitaxel followed by Gemcitabine Hydrochloride in Treating Pediatric Participants with Newly-Diagnostic, Relapsed or Refractory Solid Tumors

Trial Status: Active

This phase I trial studies the side effects and best dose of nab-paclitaxel when given together with gemcitabine hydrochloride in treating pediatric participants with solid tumors that are newly-diagnostic, have come back (relapsed), or do not respond to treatment (refractory). Nab-paclitaxel may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, or by stopping them from dividing, or by stopping them from spreading. Giving nab-paclitaxel in combination with gemcitabine hydrochloride, may work better in treating pediatric participants with solid tumors.

Inclusion Criteria

  • 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 * Note: 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 * Myelosuppressive chemotherapy: At least 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea) * Hematopoietic growth factors: 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 * Biologic (anti-neoplastic agent): 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 * Cellular therapy: >= 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.) * Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days must have elapsed from the last dose of interleukins, interferon or cytokines (other than hematopoietic growth factors) * Antibodies: >= 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 * Palliative radiation therapy (XRT): At least 14 days after local palliative XRT (small port); 6 weeks must have elapsed since treatment with therapeutic doses of 131I-metaiodobenzylguanidine (131I-MIBG); at least 42 days must have elapsed if other substantial BM radiation * Stem cell infusion without traumatic brain injury (TBI): No evidence of active graft versus (vs.) host disease and at least 84 days must have elapsed after transplant and 42 days for autologous stem cell infusion after 131I-MIBG therapy * Prior taxane and nucleoside analogue usage: Patients who have previously received a taxane, including nab-paclitaxel, or a nucleoside analogue, including gemcitabine, are eligible as long as they have not received gemcitabine in combination with nab-paclitaxel * Medical cannabis and cannabidiol (CBD oil): >= 72 hours must have elapsed since the last administration of these products * Investigational agents not otherwise specified: >= 30 days must have elapsed since the last dose of any agents not specified above; for agents with an uncertain washout period or for any questions or uncertainty the study principle investigator (PI) should be notified
  • For subjects with solid tumors without known bone marrow involvement: *Peripheral absolute neutrophil count (ANC) >= 750/mm^3
  • For subjects with solid tumors without known bone marrow involvement: *Platelet count >= 75,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
  • Adequate bone marrow function defined as: * Subjects with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); these subjects will not be evaluable for hematologic toxicity; at least 5 of every cohort of 6 patients must be evaluable for hematologic toxicity for the dose-escalation part of the study; if dose-limiting hematologic toxicity is observed, all subsequent subjects enrolled must be evaluable for hematologic toxicity
  • Creatinine clearance or radioisotope GFR 70ml/min/1.73 m^2 or
  • A serum creatinine based on age/gender as follows: * Age 6 months to < 1 year; 0.5 mg/dL (male) 0.5 mg/dL (female) * Age 1 to < 2 years; 0.6 mg/dL (male) 0.6 mg/dL (female) * Age 2 to < 6 years; 0.8 mg/dL (male) 0.8 mg/dL (female) * Age 6 to < 10 years; 1.0 mg/dL (male) 1.0 mg/dL (female) * Age 10 to < 13 years; 1.2 mg/dL (male) 1.2 mg/dL (female) * Age 13 to < 16 years; 1.5 mg/dL (male) 1.4 mg/dL (female) * Age >= 16 years; 1.7 mg/dL (male) 1.4 mg/dL (female) ** The threshold creatinine values in this table were derived from the Schwartz formula for estimating glomerular filtration rate (GFR) (Schwartz et al. J. Peds, 106:522, 1985) utilizing child length and stature data published by the Centers for Disease Control and Prevention (CDC)
  • Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age
  • Serum glutamate pyruvate transaminase (SGPT)/alanine aminotransferase measurement (ALT) =< 5 x the ULN; for the purpose of this study, the ULN for SGPT is 45 U/L

Exclusion Criteria

  • Pregnancy or breast-feeding: 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
  • Concomitant medications: * Investigational Drugs: Subjects who are currently receiving another investigational drug are not eligible * Anti-cancer Agents: Subjects who are currently receiving other anti-cancer agents are not eligible * Anti-graft-versus-host disease (GVHD) agents post-transplant: Subjects who are receiving cyclosporine, tacrolimus, or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial * Medications interfering with metabolism: ** Medications which interfere with CYP3A4 and CYP2C8 metabolism, which metabolize nab-paclitaxel: subjects using these agents are not eligible for this trial; paclitaxel is metabolized by CYP3A4 and CYP2C8, so strong inhibitors or inducers of these enzymes should be avoided *** Note on use of trimethoprim/sulfamethoxazole: Trimethoprim/sulfamethoxazole should not be administered concomitantly with abraxane/gemcitabine, and patients must be monitored closely for toxicities
  • Patients with any of the following adverse events at the time of enrollment are not eligible: * Grade >= 2 motor, sensory or peripheral neuropathy. This criteria 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 sodium [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

Florida

Saint Petersburg
Johns Hopkins All Children's Hospital
Status: ACTIVE
Contact: Jonathan Layne Metts
Phone: 727-767-2134

Georgia

Atlanta
Children's Healthcare of Atlanta - Egleston
Status: ACTIVE
Contact: William Thomas Cash
Phone: 404-785-0910

PRIMARY OBJECTIVES:

I. To estimate the recommended phase 2 dose (RP2D) or maximum tolerated dose (MTD) of nab-paclitaxel administered intravenously weekly every 3 of 4 weeks in combination with gemcitabine hydrochloride in children with refractory/relapsed non-central nervous system (CNS) solid tumors.

II. To define and describe the toxicities of nab-paclitaxel in combination with gemcitabine hydrochloride administered on this schedule.

SECONDARY OBJECTIVES:

I. To preliminarily define the anti-tumor activity of nab-paclitaxel in combination with gemcitabine hydrochloride within the confines of a phase 1 study.

II. To evaluate the expression of secreted protein acidic and rich in cysteine (SPARC) in tumor tissue from pediatric solid tumors and correlate this with response to therapy.

III. To determine the pharmacokinetic profile of nab-paclitaxel in combination with gemcitabine hydrochloride in children with refractory/relapsed non-CNS solid tumors.

OUTLINE: This is a dose escalation study of nab-paclitaxel.

Participants receive nab-paclitaxel intravenously (IV) over 30 minutes and gemcitabine hydrochloride IV over 60 minutes on days 1, 8, and 15. Cycles repeat every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed up periodically.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
Children's Healthcare of Atlanta - Egleston

Principal Investigator
William Thomas Cash

  • Primary ID AFLACST1603
  • Secondary IDs NCI-2018-00465, IRB00098777
  • Clinicaltrials.gov ID NCT03507491