A Phase 2 Study of 9-ING-41Combined With Chemotherapy in Adolescents and Adults With Advanced Sarcomas

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.
• •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.