NCT01391962

Sunitinib or Cediranib for Alveolar Soft Part Sarcoma

A Phase II Trial In Which Patients With Metastatic Alveolar Soft Part Sarcoma Are Randomized to Either Sunitinib or Cediranib Monotherapy, With Cross-Over at Disease Progression

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 34 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 16 Years – 120 Years
• Healthy volunteers: Not accepted

Summary

Background: * Alveolar soft part sarcoma (ASPS) is a rare, highly vascular tumor accounting for less than 1% of soft tissue sarcomas. There is no effective systemic treatment for patients with metastatic ASPS. Little is known with regards to relevant molecular markers as potential therapeutic targets. * Cediranib (AZD2171) and sunitinib (SU011248), oral small molecule inhibitors of vascular endothelial growth factor (VEGF) receptor tyrosine kinases, are showing preliminary evidence of activity in patients with ASPS. Objectives: * Part I: Determine the objective response rate (ORR) of single-agent cediranib and single-agent sunitinib malate in patients with advanced ASPS. * Part II: Determine the ORR of cediranib in patients who progress on the sunitinib arm, and determine the ORR of sunitinib in patients who progress on the cediranib arm. * Determine the progression-free survival (PFS) at 24 weeks for single-agent cediranib and single-agent sunitinib malate in patients with advanced ASPS. Eligibility: * Patients aged greater than or equal to 16 years with histologically or cytologically confirmed metastatic ASPS. * Patients must show evidence of objective disease progression per Response evaluation criteria in solid tumors (RECIST)v1 on scans within the 3-month period immediately preceding enrollment. Both scans used to determine disease progression should have been obtained within this 6-month period. * Patients with newly diagnosed, unresectable, measurable, metastatic ASPS who show clinical evidence of disease progression will be eligible. * Patients must not have received treatment with any VEGF receptor tyrosine kinase inhibitor (e.g., cediranib, sunitinib, pazopanib, sorafenib); however, prior treatment with bevacizumab is allowed. Design: * Part I: Patients will be randomized to receive cediranib (30 mg) or sunitinib malate (37.5 mg) orally, once a day in 28-day cycles. * Part II: At the time of disease progression, patients will cross over to the other treatment arm after a 2-week wash-out period. * Appropriate anatomic imaging studies will be performed at baseline and every 2 cycles for restaging. * The study will be conducted using an optimal two-stage design to rule out an unacceptably low 15% clinical response rate (PR+CR) in favor of a modestly high response rate of 40%. The study will initially enroll 10 evaluable patients in each arm. If 0 or 1 of the 10 patients has a clinical response, then no further patients will be accrued. If 2 or more the first 10 patients have a response, then accrual continues to a total of 22 patients in each arm.

Detailed description

Background: * Alveolar soft part sarcoma (ASPS) is a rare, highly vascular tumor accounting for less than 1% of soft tissue sarcomas. There is no effective systemic treatment for patients with metastatic ASPS. Little is known with regards to relevant molecular markers as potential therapeutic targets. * Cediranib (AZD2171) and sunitinib (SU011248), oral small molecule inhibitors of vascular endothelial growth factor (VEGF) receptor tyrosine kinases, are showing preliminary evidence of activity in patients with ASPS. Objectives: * Part I: Determine the objective response rate (ORR) of single-agent cediranib and single-agent sunitinib malate in patients with advanced ASPS. * Part II: Determine the ORR of cediranib in patients who progress on the sunitinib arm and determine the ORR of sunitinib in patients who progress on the cediranib arm. * Determine the progression-free survival (PFS) at 24 weeks for single-agent cediranib and single-agent sunitinib malate in patients with advanced ASPS. Eligibility: Status Update: Patients enrolled after Amendment G (version dated 08/16/2013), will be evaluated and compared to the first 13 patients by the study statistician and the Principal Investigator. Patients with newly diagnosed ASPS with clinical evidence of disease progression will also be assessed separately. * Patients aged greater than or equal to 16 years with histologically or cytologically confirmed metastatic ASPS. * Patients must show evidence of objective disease progression per Response Evaluation Criteria in Solid Tumors (RECIST)v 1 on scans within the 3-month period immediately preceding enrollment. Both scans used to determine disease progression should have been obtained within this 6-month period. * Patients with newly diagnosed, unresectable, measurable, metastatic ASPS who show clinical evidence of disease progression will be eligible. * Patients must not have received treatment with any VEGF receptor tyrosine kinase inhibitor (e.g., cediranib, sunitinib, pazopanib, sorafenib); however, prior treatment with bevacizumab is allowed. Design: * Two sets of patients will be enrolled and assessed in separate cohorts: a) patients with non-newly diagnosed ASPS and b) patients with newly diagnosed ASPS * Part I: Patients will be randomized to receive cediranib (30 mg) or sunitinib malate (37.5 mg) orally, once a day in 28-day cycles. As of May 6, 2019, we have closed the cediranib arm of the newly diagnosed ASPS cohort due to inadequate activity per the statistical plan; all newly diagnosed ASPS patients will be assigned to the sunitinib malate treatment arm. * Part II: At the time of disease progression, patients will cross over to the other treatment arm after a 2-week wash-out period. As of May 6, 2019, patients in the newly diagnosed ASPS cohort are not eligible to cross over to the cediranib treatment arm, which was closed due to inadequate activity. * Appropriate anatomic imaging studies will be performed at baseline and every 2 cycles for restaging. * The study will be conducted using an optimal two-stage design to rule out an unacceptably low 15% clinical response rate partial response + complete response (PR+CR) in favor of a modestly high response rate of 40%. The study will initially enroll 10 evaluable patients in each arm. If 0 or 1 of the 10 patients has a clinical response, then no further patients will be accrued. If 2 or more the first 10 patients have a response, then accrual continues to a total of 22 patients in each arm.

Conditions

• Sarcoma, Alveolar Soft Part

Interventions

Type	Name	Description
DRUG	Cediranib	Cediranib, a small molecule inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinases, is showing preliminary evidence of activity in patients with alveolar soft part sarcoma (ASPS).
DRUG	Sunitinib	Sunitinib, a small molecule inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinases, is showing preliminary evidence of activity in patients with alveolar soft part sarcoma (ASPS).
OTHER	Prochlorperazine	10mg every 6 hours orally as needed for nausea,
OTHER	Promethazine	12.5-25mg intravenous every 6 hours as needed for nausea.
OTHER	Benzodiazepine	If promethazine is inadequate, add benzodiazepine until acute nausea is controlled.
OTHER	Filgrastim	Therapeutic use per investigator's discretion according to American Society of Clinical Oncology (ASCO) guidelines.
OTHER	Sargramostim	Therapeutic use per investigator's discretion according to American Society of Clinical Oncology (ASCO) guidelines.
OTHER	Lomotil	2.5mg plus atropine sulfate 0.025mg/tablet dosed according to package insert.
OTHER	Loperamide	4mg by mouth (PO) after first unformed stool with 2mg PO every 2 hours as long as unformed stools continue.
OTHER	Vitamin B6	50-150mg orally each day for hand-foot syndrome.
OTHER	Aquaphor	Topical emollient for hand-foot syndrome.
DRUG	Acetaminophen	Analgesic for hand foot syndrome as needed.
DRUG	Levothyroxine	Replacement therapy for participants with increases in thyroid-stimulating hormone.
DRUG	Warfarin	2mg daily for prophylaxis of thrombosis.

Timeline

• Start date: 2011-07-18
• Primary completion: 2023-11-06
• Completion: 2026-01-16
• First posted: 2011-07-12
• Last updated: 2026-02-02
• Results posted: 2024-09-19

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study