Fibrosarcoma Clinical Trials

• AGE: Part A and C: ≥ 18 years of age AGE: Part B: ≥12 years (minimum BSA ≥0.55m2)

• Part A and B: Patients with unresectable or metastatic histologically confirmed NF1 associated MPNST. Part C: Patients with NF1 and ANNUBP. Diagnostic criteria based on Miettinen et al, Human Pathol:

• MEASURABLE DISEASE: Patients must have measurable disease by RECISTv1.1. Baseline radiologic scans must be performed within 4 weeks of starting treatment.

• Therapeutic options: Parts A and B: Patients must have experienced progression after one or more prior regimens of cytotoxic chemotherapy. Patients who have refused cytotoxic chemotherapy or for whom treatment on this protocol prior to receiving cytotoxic chemotherapy is felt to be in the best interest for the patient by the local investigator will also be eligible. Part C: Patients with ANNUBP that are planned for surgical resection

• PRIOR THERAPY

‣ Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering on this study excluding chronic grade 1 toxicities and alopecia.

⁃ No limitation on the number of prior chemotherapy regimens that the patient may have received prior to study entry.

⁃ Myelosuppressive chemotherapy: The last dose of all myelosuppressive anticancer drugs must be at least 3 weeks (≥21 days) prior to study entry (42 days if prior nitrosourea).

⁃ Immunotherapy: The last dose of immunotherapy (monoclonal antibody or vaccine) must be at least 4 weeks prior to study entry.

⁃ Anti-cancer agents not known to be myelosuppressive (e.g not associated with reduced platelets or ANC count): ≥7 days after the last dose of the agent .

⁃ Radiation therapy: The last dose of radiation to more than 25% of marrow containing bones (pelvis, spine, skull) must be at least 4 weeks prior to study entry. The last dose of all other local palliative (limited port) radiation must be at least 2 weeks prior to study entry.

⁃ Stem Cell Transplantation. At least 2 months post-autologous stem cell transplant or at least 3 months post-allogeneic transplant and recovered from toxicities without evidence of graft versus host disease and on stable doses of immunosuppressive medications, if required.

⁃ Growth Factors. The last dose of colony stimulating factors, such as filgrastim, sargramostim, and erythropoietin, must be at least 1 week prior to study entry, the last dose of long-acting colony stimulating factors, such as pegfilgrastim, must be at least 2 weeks prior to study entry.

• Concurrent therapies: No other anti-cancer therapy (chemotherapy, biological therapy, radiation therapy) permitted.

• PERFORMANCE STATUS

‣ Lansky/Karnofsky performance level ≥ 50% . Participants who are wheelchair bound or have limited mobility secondary to a need for mechanical breathing support (such as an airway PN requiring tracheostomy or continuous positive airway pressure) who must have a Lansky performance of ≥ 40 (Appendix related to performance status scale).

⁃ For patients ≥18: Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, with no deterioration over the previous 2 weeks prior to baseline or day of first dosing.

⁃ Patients who are unable to walk because of paralysis or motor weakness, but who are able to use a wheelchair will be considered ambulatory for the purpose of calculating the performance score.

• HEMATOLOGIC FUNCTION

‣ Hemoglobin ≥9.0 g/dL (transfusion permissible)

⁃ Peripheral absolute neutrophil count (ANC) of ≥1000/μL

⁃ Platelet count ≥75,000/μL (transfusion independent (no transfusion within at least 7 days prior to enrollment))

• HEPATIC FUNCTION

‣ Total bilirubin must be ≤ 1.5 times the upper limit of normal (ULN) or ≤3×ULN in the presence of documented Gilbert's syndrome (unconjugated hyperbilirubinemia).

⁃ SGOT (AST)/SGPT (ALT) must be ≤ 3.0 times ULN

• RENAL FUNCTION: Serum creatinine ≤ 1.5 times ULN or creatinine clearance \>60 ml/min/1.73m2

• CARDIAC FUNCTION:

‣ Normal ejection fraction by ECHO by institutional normal (within 4 weeks of enrollment)

⁃ QTc ≤ 450msec (within 4 weeks of enrollment)

• Fertile men and women of childbearing potential must agree to use an effective method of birth control.

• CNS DISEASE: Patients with central nervous system disease are eligible for enrollment if they have received prior radiotherapy or surgery to sites of CNS metastatic disease and are without evidence of clinical progression or stable disease at 4 weeks.