NCT01206140

Selumetinib With or Without Temsirolimus in Treating Patients With Metastatic, Recurrent, or Locally Advanced Soft Tissue Sarcoma That Cannot Be Removed By Surgery

Randomized, Phase II Trial of AZD6244 Alone and AZD6244 Plus Temsirolimus for Soft-Tissue Sarcomas

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 70 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This randomized phase II trial is studying how well giving selumetinib together with or without temsirolimus works in treating patients with metastatic, recurrent, or locally advanced soft tissue sarcoma that cannot be removed by surgery. Selumetinib and temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether giving selumetinib together with temsirolimus is more effective than giving selumetinib alone.

Detailed description

PRIMARY OBJECTIVES: I. Compare the progression-free survival of the MEK inhibitor, AZD6244 (selumetinib) alone, and the combination of AZD6244 and a mammalian target of rapamycin inhibitor (mTORi), temsirolimus (CCI-779) in patients with recurrent metastatic or recurrent locally unresectable soft-tissue sarcomas. SECONDARY OBJECTIVES: I. Determine the rates of apoptosis, autophagy, and proliferation with AZD6244 alone, and in combination with temsirolimus by immunohistochemistry in tumor and surrogate skin tissue biopsies. (exploratory) II. Assess the activation status of protein kinase B (Akt), 5E-BP1, eukaryotic translation initiation factor 4 gamma, 1 (eIF-4G), and ribosomal protein S6 kinase (S6K) in tumor biopsy samples and surrogate skin tissue biopsy samples.(exploratory) III. Assess inhibition of activated mitogen-activated protein kinase 1/2 (ERK1/2) in stimulated peripheral blood mononuclear cells. (exploratory) IV. Assess response by Choi criteria. V. Compare the response rate and 4-month progression-free survival (PFS) rate in patients treated with these regimens. VI. Compare the response rate, 4-month PFS rate and toxicity of AZD6244 alone and in combination with temsirolimus. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive selumetinib orally (PO) twice daily on days 1-28 and temsirolimus intravenously (IV) over 30-60 minutes on days 1, 8, 15, and 22. ARM II: Patients receive selumetinib as in arm I. Patients who experience disease progression may cross over to arm I. In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed up for 30 days.

Conditions

• Recurrent Adult Soft Tissue Sarcoma
• Stage III Adult Soft Tissue Sarcoma
• Stage IV Adult Soft Tissue Sarcoma

Interventions

Type	Name	Description
OTHER	Laboratory Biomarker Analysis	Correlative studies
DRUG	Selumetinib	Given PO
DRUG	Temsirolimus	Given IV

Timeline

• Start date: 2010-10-01
• Primary completion: 2015-04-01
• Completion: 2015-04-01
• First posted: 2010-09-21
• Last updated: 2015-10-05
• Results posted: 2015-10-05

Locations

8 sites across 1 country: United States