This phase II trial studies how well pegargiminase (ADI-PEG 20) works in combination with gemcitabine hydrochloride and docetaxel in treating patients with soft tissue sarcoma, osteosarcoma, Ewing's sarcoma, or small cell lung cancer that cannot be removed surgically (unresectable) or that has spread to other parts of the body (metastatic). ADI-PEG 20 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 and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ADI-PEG 20 with gemcitabine hydrochloride and docetaxel may work better in treating patients with soft tissue sarcoma.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03449901.
PRIMARY OBJECTIVE:
I. To determine progression-free survival in patients with soft tissue sarcoma who are treated with ADI-PEG 20 in combination with gemcitabine hydrochloride (gemcitabine) and docetaxel.
SECONDARY OBJECTIVES:
I. To determine overall survival in patients with soft tissue sarcoma who are treated with ADI-PEG 20 in combination with gemcitabine and docetaxel.
II. To determine the clinical benefit rate (CBR) of patients with soft tissue sarcoma receiving treatment with ADI-PEG 20 in combination with gemcitabine and docetaxel.
III. To evaluate the safety and tolerability of the combination of ADI-PEG 20, gemcitabine, and docetaxel (by Common Terminology Criteria for Adverse Events [CTCAE] version [v] 5.0) in soft tissue sarcoma, osteosarcoma, Ewing’s sarcoma and small cell lung cancer.
IV. To determine cancer-related mortality in patients with soft tissue sarcoma who are treated with ADI-PEG 20 in combination with gemcitabine and docetaxel.
EXPLORATORY OBJECTIVES:
I. To determine the effects of treatment with ADI-PEG 20, gemcitabine, and docetaxel on arginine, citrulline, and glutamine plasma levels.
II. To determine the rate of immunogenicity against ADI-PEG 20.
III. To evaluate the metabolomics of paired biopsies taken before and after receipt of ADI-PEG 20.
IV. To correlate response (CBR) to ADI-PEG 20 with phosphorylated (phospho)- PKM2 status.
V. To correlate response (CBR) to ADI-PEG 20 with ASS1 negativity in clinical samples.
VI. To correlate response (CBR) to ADI-PEG 20 by Choi criteria.
OUTLINE:
Patients receive pegargiminase intramuscularly (IM) on day -7 of cycle 1 and on days 1, 8, and 15 of subsequent cycles, gemcitabine hydrochloride intravenously (IV) over 90 minutes on days 1 and 8, and docetaxel IV over 60 minutes on day 8. Treatment repeats every 21 days up to week 103 (34 cycles) in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days then up to 5 years.
Lead OrganizationSiteman Cancer Center at Washington University
Principal InvestigatorMia Chana Weiss
