Inclusion Criteria:
- Stratum A: Patients must have histologically confirmed grade 2 or 3 soft tissue
sarcoma that is locally advanced and unresectable, or metastatic, consisting of one of
the following subtypes: undifferentiated pleomorphic sarcoma (malignant fibrous
histiocytoma), myxofibrosarcoma, leiomyosarcoma, liposarcoma (excluding
well-differentiated), angiosarcoma, synovial sarcoma, rhabdomyosarcoma, spindle cell
sarcoma and high-grade sarcoma NOS.
- Stratum B: Patients must have histologically confirmed bone sarcoma that is relapsed
or refractory following front-line therapy consisting of one of the following
subtypes: osteosarcoma and Ewing sarcoma.
- Patients must have at least one site of measurable disease by RECIST 1.1. See Section
12 (Measurement of Effect) for the evaluation of measurable disease.
- Stratum A: No more than three prior lines of systemic therapy. Of note,
anthracycline-based chemotherapy is generally considered first-line therapy.
Previously untreated patients may be enrolled at the discretion of the treating
investigator.
- Stratum B: At least one prior line of systemic therapy.
- Age ≥10 years.
- Lansky score ≥50 for patients <16 years or ECOG performance status ≤2 for patients ≥16
years (Karnofsky ≥50%, see Appendix A).
- Life expectancy of greater than 12 weeks.
- Patients must have adequate organ and marrow function as defined below:
- Hemoglobin ≥8 g/dl
- absolute neutrophil count ≥1,000/mcL
- platelets ≥100,000/mcL (transfusion independent)
- total bilirubin ≤1.5x institutional upper limit of normal (ULN) (<3.0 mg/dL and
direct bilirubin <1.5 mg/dL if documented Gilbert's syndrome)
- AST(SGOT)/ALT(SGPT) ≤3x institutional ULN (≤ 5 x ULN if liver metastases present)
- creatinine ≤1.5x institutional ULN OR
- glomerular filtration rate (GFR) ≥50 mL/min/1.73 m2
- PT/INR ≤1.5x institutional ULN
- Amylase and lipase ≤1.5x institutional ULN
- Washout period prior to Cycle 1, Day 1:
- ≥ 21 days since last dose of chemotherapy, immunotherapy, or therapeutic
radiation treatment.
- ≥ 28 days since last tyrosine kinase inhibitor (or 5 half-lives, whichever is
shorter).
- ≥ 7 days since last focal palliative radiation treatment.
- ≥ 28 days since major surgical procedure.
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months are eligible for this trial.
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral
load must be undetectable on suppressive therapy, if indicated.
- Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. For patients with HCV infection who are currently on treatment, they are
eligible if they have an undetectable HCV viral load.
- Women of child-bearing potential must have a negative serum or urine pregnancy test at
registration and within 7 days of first study therapy.
- The effects of 9-ING-41 on the developing human fetus are unknown. For this reason and
because other therapeutic agents used in this trial are known to be teratogenic, women
of child-bearing 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 she or her partner is participating in this study, she should inform
her treating physician immediately. Women may not be breastfeeding during study
participation. Men treated or enrolled on this protocol must also agree to use
adequate contraception prior to the study, for the duration of study participation,
and 90 days after completion of 9-ING-41 administration.
- Patients must agree to provide tumor tissue, either fresh or archival specimen of
primary tumor and/or metastatic lesion. If tumor tissue is not available, then discuss
with principal investigator.
- Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
- Patients with sarcoma histologies other than those listed above will be excluded.
- Prior treatment with 9-ING-41, gemcitabine, or docetaxel.
- Patients who have not recovered from adverse events due to prior anti-cancer therapy
(i.e., have residual toxicities > Grade 1) with the exception of alopecia.
- Patients who are receiving any other investigational agents for treatment of their
sarcoma.
- Patients who are pregnant or lactating.
- Patients with untreated brain or meningeal metastases. Subjects with history of
metastases are eligible provided they do not require ongoing steroid treatment and
have shown clinical and radiographic stability for at least 14 days after definitive
therapy.
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to 9-ING-41, gemcitabine, docetaxel, or other agents used in study.
- Patients with 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.
- Has had a previous (within 2 years) or has a current malignancy other than the target
cancer with the exception of curatively treated local tumors including carcinoma in
situ of the breast or cervix, basal or squamous cell carcinoma of the skin, or
prostate cancer with Gleason Grade < 6 and prostate-specific antigen within normal
range.
- Has any medical and/or social condition that, in the opinion of the investigator would
preclude study participation.
