Trial Search Results

ADI-PEG 20 in Combination With Gemcitabine and Docetaxel for the Treatment of Soft Tissue Sarcoma

The investigators have recently demonstrated that argininosuccinate synthase 1 (ASS1) expression is silenced in 88% of all sarcomas (n=708), and that this loss is associated with a decreased overall survival. Using the extracellular arginine depleting enzyme PEGylated arginine deiminase (ADI-PEG20), an extracellular arginine depleting enzyme, the investigators demonstrated ADI-PEG20 induces a prosurvival metabolic reprogramming in ASS1-deficient sarcomas that redirects glucose into the serine/folate pathway directing the carbons from glucose into pyrimidine biosynthesis, thus sensitizing cells to death by the pyrimidine antimetabolite gemcitabine by using metabolomics. The synthetic lethality was increased by the addition of docetaxel. Therefore a phase II clinical trial of ADI with gemcitabine and docetaxel, a standard second line therapy for soft tissue sarcoma will be conducted to determine if the clinical benefit rate of gemcitabine and docetaxel is improved by the metabolic changes induced by ADI-PEG20

Stanford is currently accepting patients for this trial.

Lead Sponsor:

Washington University School of Medicine

Collaborator: National Cancer Institute (NCI)

Stanford Investigator(s):

Intervention(s):

  • Drug: pegylated arginine deiminase
  • Drug: Gemcitabine
  • Drug: Docetaxel
  • Procedure: Tumor biopsy
  • Procedure: Research blood draw

Phase:

Phase 2

Eligibility


Inclusion Criteria:

   - 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.

   - Measurable disease defined as lesions that can be accurately measured in at least one
   dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan, as ≥ 20 mm by
   chest x-ray, or ≥ 10 mm with calipers by clinical exam.

   - Treated with at least one line of systemic therapy. The allowable window between
   treatments is 21 days for chemotherapy or a TKI, or 5 ½ 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.

   - At least 16 years of age.

   - Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

   - Normal bone marrow and organ function as defined below:

      - Leukocytes ≥ 3,000/mcL

      - Absolute neutrophil count ≥ 1,500/mcl

      - Platelets ≥ 100,000/mcl

      - Total bilirubin ≤ 2 x institutional upper limit of normal (IULN)

      - AST(SGOT)/ALT(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 m2 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 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 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 the trial.

   - Known brain metastases. Patients with known brain metastases must be excluded from
   this clinical trial because of their poor prognosis and because they often develop
   progressive neurologic dysfunction that would confound the evaluation of neurologic
   and other adverse events.

   - 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.

   - Pregnant and/or breastfeeding. Women of childbearing potential must have a negative
   pregnancy test within 14 days of study entry.

   - Known 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.

Ages Eligible for Study

16 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Behnaz Agahian
650-498-0623
Recruiting