Sunitinib or Cediranib for Alveolar Soft Part Sarcoma

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.

Conditions

• Sarcoma, Alveolar Soft Part

Interventions

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.

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Alice P Chen, M.D. · National Cancer Institute (NCI)

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

CROSSOVER

Eligibility

Min Age

16 Years

Max Age

120 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2011-07-18

Primary Completion

2023-11-06

Completion

2026-01-16

FDA Drug

Yes

Countries

• United States

Study Locations