SARC031: MEK Inhibitor Selumetinib (AZD6244) in Combination With the mTOR Inhibitor Sirolimus for Patients With Malignant Peripheral Nerve Sheath Tumors

Age ≥ 12 years of age

Patients with unresectable or metastatic histologically confirmed sporadic or NF1 associated MPNST.

Patients must have measureable disease by RECIST.

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.

Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering on this study.

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

The last dose of all myelosuppressive anticancer drugs must be at least 3 weeks prior to study entry.

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

The last dose of all biologic agents for the treatment of the patient's cancer (such as retinoids or tyrosine kinase inhibitors) must be at least 7 days prior to study entry.

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.

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.

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.

No other anti-cancer therapy (chemotherapy, biological therapy, radiation therapy) is permitted.

Karnofsky performance level ≥ 50%.

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

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)

Total bilirubin must be ≤ 1.5 times the upper limit of normal (ULN)

SGPT (ALT) must be ≤ 3.0 times ULN

Serum creatinine ≤ ULN or creatinine clearance \>60 ml/min/1.73 m2

Serum triglyceride level ≤300 mg/dL and serum cholesterol level ≤ 300 mg/dL (Patient may be on lipid-lowering medicine)

Normal ejection fraction by ECHO or cardiac MRI \>55%

QTcF ≤ 450ms

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

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.

What this study is about