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ADI-PEG 20, Gemcitabine Hydrochloride and Docetaxel in Treating Patients with Unresectable or Metastatic Soft Tissue Sarcoma, Osteosarcoma, Ewing’s sarcoma, or Small Cell Lung Cancer

Trial Status: Active

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.

Inclusion Criteria

  • Cohort 1: Histologically or cytologically confirmed grade 2 or 3 soft tissue sarcoma that is unresectable or metastatic that would be standardly treated with gemcitabine or gemcitabine and docetaxel; for all others, please contact the principal investigator; prior surgery for primary or metastatic disease after chemotherapy following a response is allowed
  • Cohort 2: Histologically or cytologically confirmed osteosarcoma, Ewing’s sarcoma, or small cell lung cancer that is unresectable or metastatic that have either failed standard of care therapy or would be standardly treated with gemcitabine or gemcitabine and docetaxel
  • Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 10 mm with computed tomography (CT) scan, as >= 20 mm by chest x-ray, or >= 10 mm with calipers by clinical exam
  • Treated with at least one previous line of systemic therapy; the allowable window between treatments is 21 days for chemotherapy or a tyrosine kinase inhibitor (TKI) or 5 half-lives for a TKI (whichever is shorter), 21 days and progression by CT for immunotherapy, 21 days for RT, 21 days for surgery, or 28 days for an investigational agent
  • Cohort 1: At least 16 years of age
  • Cohort 2: Patients with osteosarcoma or Ewing’s sarcoma must be at least 10 years of age; patients with small cell lung cancer must be at least 18 years of age
  • Cohort 2 (small cell lung cancer [SCLC] group ONLY): Must be amenable to biopsy
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcl
  • Platelets >= 100,000/mcl
  • Total bilirubin =< 2 x institutional upper limit of normal (IULN)
  • Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT)/alanine aminotransferase (ALT) serum glutamic-pyruvic transaminase (SGPT) =< 3 x IULN (or =< 5 x IULN if liver metastases are present)
  • Creatinine =< 1.5 x IULN OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Serum uric acid =< 8 mg/dL (with or without medication control)
  • Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately
  • Ability to understand and willingness to sign an Institutional Review Board (IRB) approved written informed consent document (or that of legally authorized representative, if applicable)

Exclusion Criteria

  • A history of other high grade malignancy =< 5 years previous; exceptions include basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix, or other tumors discussed with the study principal investigator (PI)
  • Currently receiving any other investigational agents
  • Prior treatment with ADI-PEG 20, gemcitabine, or docetaxel; patients treated > one year ago in the adjuvant/neoadjuvant setting with gemcitabine or docetaxel would be allowed to be enrolled on trial
  • Known brain metastases; patients with known brain metastases must be excluded from this clinical trial (except for patients with SCLC) because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events; patients with SCLC are allowed to enroll with brain metastases provided they are stable and they are at least 3 months post-treatment for brain metastases
  • A history of allergic reactions attributed to compounds of similar chemical or biologic composition to ADI-PEG 20, gemcitabine, pegylated compounds, or other agents used in the study
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • History of seizure disorder not related to underlying cancer
  • Patients with grade 2 or higher neuropathy
  • Pregnant and/or breastfeeding; women of childbearing potential must have a negative pregnancy test within 14 days of study entry
  • Known human immunodeficiency virus (HIV)-positivity on combination antiretroviral therapy because of the potential for pharmacokinetic interactions with the study treatment; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated

California

Palo Alto
Stanford Cancer Institute Palo Alto
Status: ACTIVE
Contact: Nam Bui
Phone: 713-412-8721
Santa Monica
Sarcoma Oncology Center
Status: ACTIVE
Contact: Steven Wong
Phone: 310-552-9999

Missouri

Saint Louis
Siteman Cancer Center at Washington University
Status: ACTIVE
Contact: Brian Andrew Van Tine
Phone: 314-747-3096

New York

New York
Columbia University Medical Center MBCCOP
Status: ACTIVE
Contact: Gary K. Schwartz
Phone: 212-305-2055

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.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Siteman Cancer Center at Washington University

Principal Investigator
Brian Andrew Van Tine

  • Primary ID 201912062-1001
  • Secondary IDs NCI-2018-00565, 201803202
  • Clinicaltrials.gov ID NCT03449901