ADI-PEG 20 will be given on Day -7 of Cycle 1 and then on Days 1, 8, and 15 of each subsequent cycle. Cycles are 21 days. ADI-PEG 20 will be given on an outpatient basis at a dose of 36 mg/m2 via intramuscular injection into either the deltoid or gluteal muscle.
Gemcitabine will be given intravenously at a dose of 600 mg/m2 over 90 minutes on Days 1 and 8 of each cycle. Docetaxel will be given intravenously at a dose of 60 mg/m2 over 60 minutes on Day 8 of each cycle. Patients started on gemcitabine at a dose of 900 mg/m2 or 750 mg/m2 or docetaxel at a dose of 75 mg/m2 per previous protocol version will be allowed to continue at that dose level
After Cycle 8, patients may continue on ADI-PEG 20 alone (without gemcitabine and docetaxel) upon request.
Treatment may continue for up to 34 cycles (103 weeks)

Soft Tissue Sarcoma

-Arginine deiminase (ADI) is a recombinant protein cloned from M. hominis, produced in E. coli, and conjugated with PEG of 20,000 mw using a succinimidyl succinate linker. Thus ADI-PEG 20 is an arginine degrading enzyme, ADI, coupled to PEG.

pegylated arginine deiminase

-Gemcitabine is a nucleoside metabolic inhibitor that exhibits antitumor activity.

Gemcitabine

-Docetaxel is an antineoplastic agent belonging to the taxoid family. It is prepared by semisynthesis beginning with a precursor extracted from the renewable needle biomass of yew plants.

Docetaxel

Up to 21 days prior to initiation of ADI-PEG 20 Day -1 (+/- 1 day as long as performed prior to initiation of gemcitabine.
Tumor biopsies are mandatory for the first 20 patients amendable to biopsy enrolled at Washington University only (completed as of 05/14/2019) and for all patients enrolled to the SCLC cohort

Tumor biopsy

-Day -7 (pre-treatment), Day -1, and Days 1 and 8 of each cycle

Research blood draw

Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Stanford Medicine

Sarcoma Oncology Center

Washington University School of Medicine

Columbia University Medical Center

ADI-PEG 20 in Combination With Gemcitabine and Docetaxel for the Treatment of Soft Tissue Sarcoma, Osteosarcoma, Ewing's Sarcoma, and Small Cell Lung Cancer

A Phase II Trial of ADI-PEG 20 in Combination With Gemcitabine and Docetaxel for the Treatment of Soft Tissue Sarcoma Osteosarcoma, Ewing's Sarcoma, and Small Cell Lung Cancer

PFS: defined as time on study to time patients progressed on the drug combination or death or latest follow-up if progression/death is not observed yet
Progressive disease: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).

-OS: defined as time on study to time of death due to any reasons or latest follow-up (whichever is earlier)

CBR = proportion of patients who have experienced complete response (CR)+ partial response (PR) + stable disease (SD) lasting 24 weeks or longer
CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis).
PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

-The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for all toxicity reporting.

National Institutes of Health (NIH)

National Cancer Institute (NCI)

IV administration of drugs for 14 days for up to 4 cycles

IV administration of drugs for 14 days for up to 4 cycles
Alimta: 500 mg/m2 via IV over 10 minutes
A chemotherapy drug with indications to treat pleural mesothelioma and non-small cell lung cancer.
Gemcitabine: 1000 mg/m2 via IV over 90 minutes
A nucleoside analog used as chemotherapy.

Alimta/Gemcitabine

Age, Customized

Sex/Gender, Customized

Race/Ethnicity, Customized

Region of Enrollment

The best response rate will include patients with both Complete Response and Partial Response after 2 months of treatment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Tumor Best Response Rate

Overall Study

Rober Taub, MD - Vivian and Seymour Milstein Family Prof. of Clinical Medicine

Sarcoma, Soft Tissue

500 mg/m2 via IV over 10 minutes
A chemotherapy drug with indications to treat pleural mesothelioma and non-small cell lung cancer.

Alimta

1000 mg/m2 via IV over 90 minutes
A nucleoside analog used as chemotherapy.

Alimta Plus Gemcitabine for Advanced Sarcoma

Alimta Plus Gemcitabine as Chemotherapy for Patients With Advanced Sarcoma: A Phase II Clinical

Columbia University

Sarcoma

Bone Tumor

Patients will undergo DCE-MRI prior to, and within 18-24 days of starting chemotherapy. These studies are designed to determine if the DCE-MRI data will provide an a priori or early prognostic marker of tumor response. The dynamic MRI is done on a standard clinical scanner using standard techniques described below.
MR imaging studies will be acquired on a 1.5T GE (Milwaukee,WI) Signa LX scanner.

folate/sarkoma

ADI-PEG 20 in Combination With Gemcitabine and Docetaxel for the Treatment of Soft Tissue Sarcoma, Osteosarcoma, Ewing's Sarcoma, and Small Cell Lung Cancer

Alimta Plus Gemcitabine for Advanced Sarcoma

Dynamic Contrast Enhanced MRI(DCE-MRI)of Bone Tumors

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