Sunitinib or Cediranib for Alveolar Soft Part Sarcoma

NCT01391962 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 11020011-C-0200
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

Pharmacodynamics; VEGF Inhibitor; Alveolar Soft Part Sarcoma; Anti-Angiogenesis; Gene Expression Profiling

Outcome Measures

Primary Outcomes (4)

• Part I: Objective Response Rate (ORR) of Single-agent Cediranib in Participants With Advanced Alveolar Soft Part Sarcoma (ASPS)

  Objective response rate is the combined partial and complete response rate, with those terms defined by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Complete response is disappearance of all non-target lesion and normalization of tumor marker level. Partial response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum of the LD.

  Time on treatment (an average of 497 days or 16 months)

• Part I: Objective Response Rate (ORR) of Single-agent Sunitinib in Participants With Advanced Alveolar Soft Part Sarcoma (ASPS)

  Objective response rate is the combined partial and complete response rate, with those terms defined by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Complete response is disappearance of all non-target lesion and normalization of tumor marker level. Partial response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum of the LD.

  Time on treatment (an average of 497 days or 16 months)

• Part II: Objective Response Rate (ORR) of Sunitinib in Participants Who Progress on the Cediranib Arm During Part I

  Objective response rate is the combined partial and complete response rate, with those terms defined by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Complete response is disappearance of all non-target lesion and normalization of tumor marker level. Partial response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum of the LD.

  Time on treatment (an average of 497 days or 16 months)

• Part II: Objective Response Rate (ORR) of Cediranib in Participants Who Progress on the Sunitinib Arm During Part I

  Objective response rate is the combined partial and complete response rate, with those terms defined by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Complete response is disappearance of all non-target lesion and normalization of tumor marker level. Partial response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum of the LD.

  Time on treatment (an average of 497 days or 16 months)

Secondary Outcomes (3)

• Maximum Observed Plasma Concentration of Cediranib

  Before first dose on Cycle 1 day 15, Cycle 2 Day 1, Cycle 3 Day 1, and Cycle 4 Day 1 (each cycle is 28 days)

• 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

  24 weeks

• Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0).

  Date treatment consent signed to date off study, an average of 523 days

Other Outcomes (4)

• Best Overall Response During Part I for Participants Who Were Not Newly Diagnosed

  Time on treatment (an average of 497 days or 16 months)

• Percentage of Participants With Progression-free Survival (PFS) at 24 Weeks During Part I for Participants Who Were Not Newly Diagnosed

  24 weeks

• Best Overall Response During Part II for Participants Who Were Not Newly Diagnosed

  Time on treatment (an average of 497 days or 16 months)

Study Arms (2)

Part I - Cediranib (30 mg) or Sunitinib Malate (37.5 mg) Orally

EXPERIMENTAL

Patients will be randomized to receive cediranib (30 mg) or sunitinib malate (37.5 mg) orally, once a day in 28-day cycles.

Drug: Cediranib; Drug: Sunitinib; Other: Prochlorperazine; Other: Promethazine; Other: Benzodiazepine; Other: Filgrastim; Other: Sargramostim; Other: Lomotil; Other: Loperamide; Other: Vitamin B6; Other: Aquaphor; Drug: Acetaminophen; Drug: Levothyroxine; Drug: Warfarin

Part II - Cross Over

EXPERIMENTAL

At the time of disease progression, patients will cross over to the other treatment arm after a 2-week wash-out period.

Drug: Cediranib; Drug: Sunitinib; Other: Prochlorperazine; Other: Promethazine; Other: Benzodiazepine; Other: Filgrastim; Other: Sargramostim; Other: Lomotil; Other: Loperamide; Other: Vitamin B6; Other: Aquaphor; Drug: Acetaminophen; Drug: Levothyroxine; Drug: Warfarin

Interventions

Cediranib DRUG

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).

Also known as: AZD2171 maleate, Recentin, AXD2171

Part I - Cediranib (30 mg) or Sunitinib Malate (37.5 mg) Orally; Part II - Cross Over

Sunitinib DRUG

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).

Also known as: Sutent, SU11248, SU011248

Part I - Cediranib (30 mg) or Sunitinib Malate (37.5 mg) Orally; Part II - Cross Over

Prochlorperazine OTHER

10mg every 6 hours orally as needed for nausea,

Also known as: Compro

Part I - Cediranib (30 mg) or Sunitinib Malate (37.5 mg) Orally; Part II - Cross Over

Promethazine OTHER

12.5-25mg intravenous every 6 hours as needed for nausea.

Also known as: Phenadoz, Phenergan, Promethegan

Part I - Cediranib (30 mg) or Sunitinib Malate (37.5 mg) Orally; Part II - Cross Over

Benzodiazepine OTHER

If promethazine is inadequate, add benzodiazepine until acute nausea is controlled.

Also known as: Valium, Diazepam, Estazolam, ProSom, Flurazepam, Dalmane, Lorazepam, Ativan

Part I - Cediranib (30 mg) or Sunitinib Malate (37.5 mg) Orally; Part II - Cross Over

Filgrastim OTHER

Therapeutic use per investigator's discretion according to American Society of Clinical Oncology (ASCO) guidelines.

Also known as: Neupogen

Part I - Cediranib (30 mg) or Sunitinib Malate (37.5 mg) Orally; Part II - Cross Over

Sargramostim OTHER

Therapeutic use per investigator's discretion according to American Society of Clinical Oncology (ASCO) guidelines.

Also known as: Leukine

Part I - Cediranib (30 mg) or Sunitinib Malate (37.5 mg) Orally; Part II - Cross Over

Lomotil OTHER

2.5mg plus atropine sulfate 0.025mg/tablet dosed according to package insert.

Also known as: Diphenoxylate hydrochloride (HCL)/atropine

Part I - Cediranib (30 mg) or Sunitinib Malate (37.5 mg) Orally; Part II - Cross Over

Loperamide OTHER

4mg by mouth (PO) after first unformed stool with 2mg PO every 2 hours as long as unformed stools continue.

Also known as: Imodium, Diamode, Anti-Diarrheal (loperamide)

Part I - Cediranib (30 mg) or Sunitinib Malate (37.5 mg) Orally; Part II - Cross Over

Vitamin B6 OTHER

50-150mg orally each day for hand-foot syndrome.

Also known as: Pyridoxine

Part I - Cediranib (30 mg) or Sunitinib Malate (37.5 mg) Orally; Part II - Cross Over

Aquaphor OTHER

Topical emollient for hand-foot syndrome.

Part I - Cediranib (30 mg) or Sunitinib Malate (37.5 mg) Orally; Part II - Cross Over

Acetaminophen DRUG

Analgesic for hand foot syndrome as needed.

Also known as: Tylenol, Ofirmev, FeverAll

Part I - Cediranib (30 mg) or Sunitinib Malate (37.5 mg) Orally; Part II - Cross Over

Levothyroxine DRUG

Replacement therapy for participants with increases in thyroid-stimulating hormone.

Also known as: Synthroid, Tirosint, Unithroid

Part I - Cediranib (30 mg) or Sunitinib Malate (37.5 mg) Orally; Part II - Cross Over

Warfarin DRUG

2mg daily for prophylaxis of thrombosis.

Also known as: Coumadin

Part I - Cediranib (30 mg) or Sunitinib Malate (37.5 mg) Orally; Part II - Cross Over

Eligibility Criteria

• Age: 16 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Patients must not have received prior treatment with any VEGF receptor tyrosine kinase inhibitor (e.g., cediranib, sunitinib, pazopanib, sorafenib); however, prior treatment with bevacizumab is allowed.
• Patients may not be receiving any other investigational agents.
• Major surgery within 4 weeks prior to entry into the study, or a surgical incision that is not fully healed.
• History of familial long QT syndrome, or use of medications that may cause QTc interval prolongation.
• Patients with a pre-existing thyroid abnormality who are unable to maintain thyroid function in the normal range with medication are ineligible.
• Warfarin and its derivatives are not allowed. Patient can be receiving low molecular weight heparin if clinically indicated.
• Uncontrolled intercurrent illness including, but not limited to hypertension, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patients with any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow, retain, and/or absorb the drug are excluded.
• Patients with any of the following conditions are excluded: serious or non-healing wound, ulcer; history of abdominal fistula, gastrointestinal perforation, or intra - abdominal abscess within 28 days of treatment; coronary/peripheral artery bypass graft or stenting within the past 12 months; or cerebrovascular accident (CVA) or transient ischemic attack within the past 12 months.
• Greater than 2+ proteinuria on two consecutive dipsticks taken no less than 1 week apart or 24-hour urine protein of \> 1 g. Patients with \< 2+ proteinuria are eligible following initial determination by urinalysis within 1 week prior to enrollment and do not need the urinalysis repeated.
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for PK interactions with cediranib or sunitinib. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Anderson ME, Hornicek FJ, Gebhardt MC, Raskin KA, Mankin HJ. Alveolar soft part sarcoma: a rare and enigmatic entity. Clin Orthop Relat Res. 2005 Sep;438:144-8. doi: 10.1097/01.blo.0000180049.50832.4a.

  PMID: 16131883 BACKGROUND

• Azizi AA, Haberler C, Czech T, Gupper A, Prayer D, Breitschopf H, Acker T, Slavc I. Vascular-endothelial-growth-factor (VEGF) expression and possible response to angiogenesis inhibitor bevacizumab in metastatic alveolar soft part sarcoma. Lancet Oncol. 2006 Jun;7(6):521-3. doi: 10.1016/S1470-2045(06)70729-X. No abstract available.

  PMID: 16750504 BACKGROUND

• Bello CL, Sherman L, Zhou J, Verkh L, Smeraglia J, Mount J, Klamerus KJ. Effect of food on the pharmacokinetics of sunitinib malate (SU11248), a multi-targeted receptor tyrosine kinase inhibitor: results from a phase I study in healthy subjects. Anticancer Drugs. 2006 Mar;17(3):353-8. doi: 10.1097/00001813-200603000-00015.

  PMID: 16520665 BACKGROUND

• Nguyen J, Takebe N, Kummar S, Razak A, Chawla SP, George S, Patel SR, Keohan ML, Movva S, O'Sullivan Coyne G, Do K, Juwara L, Augustine B, Steinberg SM, Kuhlmann L, Ivy SP, Doroshow JH, Chen AP. Randomized Phase II Trial of Sunitinib or Cediranib in Alveolar Soft Part Sarcoma. Clin Cancer Res. 2023 Apr 3;29(7):1200-1208. doi: 10.1158/1078-0432.CCR-22-2145.

  PMID: 36302173 RESULT

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Sarcoma, Alveolar Soft Part

Interventions

cediranib; Sunitinib; Prochlorperazine; Promethazine; Diphenhydramine; Benzodiazepines; Diazepam; Estazolam; Flurazepam; Lorazepam; Filgrastim; sargramostim; atropine sulfate-diphenoxylate hydrochloride drug combination; Diphenoxylate; Loperamide; Vitamin B 6; Pyridoxine; Petrolatum; Acetaminophen; Thyroxine; Warfarin

Condition Hierarchy (Ancestors)

Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Phenothiazines; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Propylamines; Amines; Ethylamines; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Benzazepines; Benzodiazepinones; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Isonipecotic Acids; Acids, Heterocyclic; Piperidines; Picolines; Pyridines; Acetanilides; Anilides; Amides; Aniline Compounds; Thyroid Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; 4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans

Results Point of Contact

• Title: Dr. Alice P. Chen
• Organization: National Cancer Institute

chenali@mail.nih.gov

240-781-3320

Study Officials

• Alice P Chen, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Investigator

Study Record Dates

• First Submitted: July 9, 2011
• First Posted: July 12, 2011
• Study Start: July 18, 2011
• Primary Completion: November 6, 2023
• Study Completion: January 16, 2026
• Last Updated: February 2, 2026
• Results First Posted: September 19, 2024

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely.
• Access Criteria: Requests for all collected individual participant data (IPD) data from clinical trials, conducted under a binding collaborative agreement between national Cancer Institute (NCI)/Division of Cancer Treatment and Diagnosis (DCTD) and a pharmaceutical/biotechnology company, that are not under Data and Safety Monitoring Board (DSMB) monitoring must be in compliance with the terms of the binding collaborative agreement and must be approved by NCI/DCTD and the Pharmaceutical Collaborator (i.e., the NCI Experimental Therapeutics Clinical Trials Network (ETCTN) Director in conjunction with the NCI/DCTD Regulatory Affairs Branch).

Locations

US (1)