SARC031: A Phase 2 Trial of the MEK Inhibitor Selumetinib (AZD6244 Hydrogen Sulfate) in Combination With the mTOR Inhibitor Sirolimus for Patients With Unresectable or Metastatic Malignant Peripheral Nerve Sheath Tumors
Overview
- Phase
- Phase 2
- Intervention
- Selumetinib
- Conditions
- Malignant Peripheral Nerve Sheath Tumors
- Sponsor
- Sarcoma Alliance for Research through Collaboration
- Enrollment
- 21
- Locations
- 5
- Primary Endpoint
- Clinical benefit rate of selumetinib in combination with sirolimus in patients with unresectable or metastatic NF1 associated or sporadic MPNST.
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
To determine the clinical benefit rate of selumetinib in combination with sirolimus in patients with unresectable or metastatic neurofibromatosis type 1 (NF1) associated or sporadic MPNST.
Detailed Description
I. Primary Objective • To determine the clinical benefit rate of selumetinib in combination with sirolimus in patients with unresectable or metastatic NF1 associated or sporadic MPNST II. Secondary Objective(s) * To define and describe the toxicities of selumetinib in combination with sirolimus in patients with unresectable or metastatic NF1 associated or sporadic MPNST. * To assess the impact on intensity and pain interference and correlate to changes in clinical, imaging response and progression * To assess progression free and overall survival Selumetinib will be given orally 50mg twice daily continuously and sirolimus will be given orally 4mg once daily with a cycle 1 day 1 loading dose of 12mg. One cycle will be 28 days. Patients will be able to remain on treatment as long as they do not experience progressive disease or unacceptable toxicity. Stage 1 will require 7 patients, with no further accrual if 0 of 7 respond. If 1 or greater of the 7 patients respond, accrual will continue until 21 patients have been enrolled.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
Exclusion Criteria
- •Patients receiving other anti-cancer agents are not eligible.
- •Patients who cannot swallow whole pills.
- •Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent (for example cyclosporine). Topical or inhaled corticosteroids are allowed.
- •Patients should not receive immunizations with attenuated live vaccines within four weeks of study entry or during study period.
- •Any recent major surgery within a minimum of 4 weeks, with the exception of surgical placement for vascular access, or minor surgery (excluding tumor biopsies) within 14 days.
- •Patients who any known severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
- •Severely impaired lung function defined as spirometry and DLCO that is 50% of the normal predicted value corrected for hemoglobin and alveolar volume and/or O2 saturation that is 88% or less at rest on room air. For patients who do NOT have respiratory symptoms (e.g. dyspnea at rest, known requirement for supplemental oxygen), pulmonary function test is not required.
- •Cardiac conditions as follows:
- •Uncontrolled hypertension (blood pressure ≥150/95 mmHg despite medical therapy).
- •Acute coronary syndrome within 6 months prior to starting treatment
Arms & Interventions
Selumetinib and Sirolimus
A Simon's two-stage phase 2 trial of MEK inhibitor selumetinib in combination with the mTOR inhibitor sirolimus to determine the safety and clinical benefit in patients with unresectable or metastatic MPNSTs. Both agents will be given orally on an empty stomach. Selumetinib will be given orally at a dose of 50mg twice daily continuously. Sirolimus will be given orally at a dose of 4mg once daily with a cycle 1 day 1 loading dose of 12mg. Each cycle will be considered 28 days.
Intervention: Selumetinib
Selumetinib and Sirolimus
A Simon's two-stage phase 2 trial of MEK inhibitor selumetinib in combination with the mTOR inhibitor sirolimus to determine the safety and clinical benefit in patients with unresectable or metastatic MPNSTs. Both agents will be given orally on an empty stomach. Selumetinib will be given orally at a dose of 50mg twice daily continuously. Sirolimus will be given orally at a dose of 4mg once daily with a cycle 1 day 1 loading dose of 12mg. Each cycle will be considered 28 days.
Intervention: Sirolimus
Outcomes
Primary Outcomes
Clinical benefit rate of selumetinib in combination with sirolimus in patients with unresectable or metastatic NF1 associated or sporadic MPNST.
Time Frame: Up to 6 months
An evaluable patient will be classified as a responder if the patient achieves a partial response (PR), complete response (CR) or stable disease (SD) ≥ 4 cycles.
Secondary Outcomes
- Assess the impact on pain severity(Up to 6 months)
- Progression free and overall survival(Progression-Free Survival (PFS) is defined as the duration of time from the start of treatment to the time of objective progression or death. [Time Frame: Up to 4 years])
- Define and describe the toxicities of selumetinib in combination with sirolimus in patients with unresectable or metastatic NF1 associated or sporadic MPNST.(Up to 6 months)
- Assess the impact on pain interference(Up to 6 months)