Phase 2 N=34 Randomized Treatment

Sunitinib or Cediranib for Alveolar Soft Part Sarcoma

Sarcoma, Alveolar Soft Part

Bottom Line

View on ClinicalTrials.gov: NCT01391962 ↗

Enrolled (actual)

Serious AEs

25.0%

Results posted

Sep 2024

Primary outcome: Primary: Part I: Objective Response Rate (ORR) of Single-agent Cediranib in Participants With Advanced Alveolar Soft Part Sarcoma (ASPS) — 0; 0; 0; 1 Participants

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Cediranib (Drug); Sunitinib (Drug); Prochlorperazine (Other); Promethazine (Other); Benzodiazepine (Other); Filgrastim (Other); Sargramostim (Other); Lomotil (Other); Loperamide (Other); Vitamin B6 (Other); Aquaphor (Other); Acetaminophen (Drug); Levothyroxine (Drug); Warfarin (Drug)
Age: Pediatric, Adult, Older Adult · 16+ yrs
Sex: All
Sponsor: National Cancer Institute (NCI)
Primary completion: Nov 2023

Outcome Measures

Outcome	Result	p-value
PRIMARY Part I: Objective Response Rate (ORR) of Single-agent Cediranib in Participants With Advanced Alveolar Soft Part Sarcoma (ASPS)	0; 0; 0; 1	—
PRIMARY Part I: Objective Response Rate (ORR) of Single-agent Sunitinib in Participants With Advanced Alveolar Soft Part Sarcoma (ASPS)	0; 0; 0; 1	—
PRIMARY Part II: Objective Response Rate (ORR) of Sunitinib in Participants Who Progress on the Cediranib Arm During Part I	0; 0	—
PRIMARY Part II: Objective Response Rate (ORR) of Cediranib in Participants Who Progress on the Sunitinib Arm During Part I	0; 1	—
SECONDARY Maximum Observed Plasma Concentration of Cediranib	108; 115; 126	—
SECONDARY Percentage of Participants With Progression-free Survival (PFS) at 24 Weeks for Participants Receiving Single-agent Cediranib and Single-agent Sunitinib Malate in Participants With Advanced ASPS During Part I	62.5; 62.5; 50.0; 50.0	—
SECONDARY Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0).	7; 9; 4; 13	—

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.

Eligibility Criteria

INCLUSION CRITERIA:

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 must have histologically confirmed metastatic alveolar soft part sarcoma that is not curable by surgery. Diagnosis of malignancy must be confirmed by the department of pathology at the institution where the patient is enrolled prior to patient enrollment.
Patients must show evidence of objective disease progression per Response Evaluation Criteria in Solid Tumors (RECIST)v 1 on scans within the 6-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, metastatic, and measurable alveolar soft part sarcoma (ASPS) who show clinical evidence of disease progression (including history and increasing physical symptoms) will also be eligible. On-study documentation will include a physician's rationale that supports evidence of clinical disease progression (i.e., increasing tumor pain).
Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as greater than or equal to 20 mm with conventional techniques or as greater than or equal to 10 mm with spiral computed tomography (CT) scan.
Any prior therapy must have been completed greater than or equal to 4 weeks prior to enrollment on protocol and the participant must have recovered to eligibility levels from prior toxicity. Patients should be at least 6 weeks out from nitrosoureas and mitomycin C. Prior radiation should have been completed greater than or equal to 4 weeks prior to study enrollment and all associated toxicities resolved to eligibility levels. Patients who have had prior monoclonal antibody therapy must have completed that therapy at least 3 half-lives of the antibody or 6 weeks ago. Patients who have received more than a cumulative dose of 350 mg/m(2) of doxorubicin may be enrolled at the discretion of the Coordinating Center PI after consultation with a cardiologist and if screening echocardiogram is normal.
Patients must be greater than or equal to 2 weeks since any investigational agent administered as part of a Phase 0 study (also referred to as an early Phase I study or pre-Phase I study where a sub-therapeutic dose of drug is administered) at the Coordinating Center principal investigator (PI's) discretion and should have recovered to eligibility levels from any toxicities.
Patients with no prior therapy are eligible, provided they have metastatic disease that is not curable by surgery.
Age greater than or equal to 16 years. Patients age 16-17 years are eligible only if they have a BSA greater than or equal to 1.7 m(2) or weigh greater than or equal to 60 kg.
Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.
Life expectancy of greater than 3 months.
Patients must have normal organ and marrow function as defined below:
leukocytes greater than or equal to 3,000/mcL
absolute neutrophil count greater than or equal to 1,500/mcL
platelets greater than or equal to 100,000/mcL
hemoglobin greater than or equal to 9 g/dL
total serum bilirubin within normal institutional limits
aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT)/alanine aminotransferase (ALT) serum glutamate-pyruvate transaminase (SGPT) less than or equal to 2.5 times institutional upper limit of normal
creatinine within normal institutional limits

creatinine clearance greater than or equal to 60 mL/min for patients with creatinine levels above institutional normal
QT corrected for heart rate (QTc) 1 g. Patients with < 2+ proteinuria are eligible following initial determination by urinalysis within 1 week prior to enrollment and do not need th

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Data sourced from ClinicalTrials.gov (NCT01391962). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.