Relapsed and refractory non-central nervous system (non-CNS) solid tumors have poor outcomes, and novel therapies are needed. Many relapsed/refractory solid tumor patients desire further therapy; however, they often wish to also preserve a high quality of life. Thus therapeutic strategies that offer relatively minimal treatment-related toxicities are also desirable. The combination of gemcitabine, a pyrimidine analog, and docetaxel, an antimitotic taxane, is an attractive combination because of non-overlapping toxicities. This combination has shown activity and tolerability in adult Phase II trials for solid tumors. Favorable experiences with this regimen in pediatrics have been described retrospectively by several institutions. Nab-paclitaxel is an albumin-bound, solvent-free taxane that allows higher dosing and shorter infusion duration than solvent-bound taxanes (docetaxel and paclitaxel) by removing exposure to toxic solvent carriers. Albumin binding of the agent also increases drug delivery to tumors through increased albumin-initiated transcytosis, and may also increase tumoral accumulation of drug through binding of secreted protein acidic and rich in cysteine (SPARC). The combination of gemcitabine and nab-paclitaxel has been studied extensively in adults with pancreatic adenocarcinoma, with the combination providing superior outcomes to treatment with gemcitabine alone. There is also preclinical evidence of potent anti-tumor activity of nab-paclitaxel alone and in combination with gemcitabine in pediatric solid tumor models. Therefore, the researchers hypothesize that the combination of nab-paclitaxel with gemcitabine will improve the anti-tumor efficacy observed with gemcitabine/docetaxel in relapsed/refractory solid tumors.

This is a Phase 1 study of nab-paclitaxel in combination with gemcitabine for children, adolescents, and young adults with relapsed or refractory non-central nervous system (CNS) solid tumors in which the researchers will define toxicity, pharmacokinetics, and evaluate SPARC expression in pediatric tumors as a biomarker of disease response.

Nab-paclitaxel will be administered intravenously (IV) once weekly on days 1,8, and 15 of a 28 day cycle. The starting dose of nab-paclitaxel will be 180 mg/m2/dose which is 75% of the pediatric, single agent MTD of 240 mg/m2/dose. The researchers will then dose escalate up to 240 mg/m2/dose. Dose Level 1 of the protocol prior to Amendment 2 utilized nab-paclitaxel at 180 mg/m2/dose and gemcitabine and 1000 mg/m2/dose given on days 1, 8, and 15 of 28 day cycles. The study enrolled 5 patients at Dose Level 1 and two patients experienced hematologic dose limiting toxicities (DLTs). Amendment 2 decreases the starting dose of gemcitabine on Dose Level 1 to 675 mg/m2/dose on days 1, 8, and 15 of the 28 day cycle. If Dose Level 1 is tolerated, then the dose of nab-paclitaxel will escalated on subsequent dose levels. If two or more participants experience DLTs at Dose Level 1, then the study will de-escalate to Dose Level 0 by decreasing the gemcitabine dose to 500 mg/m2/dose IV days 1, 8, and 15. If Dose Level 0 is tolerated, then a dose escalation of nab-paclitaxel will occur.

Participants may continue on therapy until there is evidence of progressive disease or toxicity that requires removal from therapy. Therapy may otherwise continue for up to 24 cycles.