Sarcoma, Alveolar Soft Part
Conditions
Keywords
Pharmacodynamics, VEGF Inhibitor, Alveolar Soft Part Sarcoma, Anti-Angiogenesis, Gene Expression Profiling
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.
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.
Interventions
DRUGCediranib
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).
DRUGSunitinib
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).
OTHERProchlorperazine
10mg every 6 hours orally as needed for nausea,
OTHERPromethazine
12.5-25mg intravenous every 6 hours as needed for nausea.
OTHERBenzodiazepine
If promethazine is inadequate, add benzodiazepine until acute nausea is controlled.
OTHERFilgrastim
Therapeutic use per investigator's discretion according to American Society of Clinical Oncology (ASCO) guidelines.
OTHERSargramostim
Therapeutic use per investigator's discretion according to American Society of Clinical Oncology (ASCO) guidelines.
OTHERLomotil
2.5mg plus atropine sulfate 0.025mg/tablet dosed according to package insert.
OTHERLoperamide
4mg by mouth (PO) after first unformed stool with 2mg PO every 2 hours as long as unformed stools continue.
OTHERVitamin B6
50-150mg orally each day for hand-foot syndrome.
OTHERAquaphor
Topical emollient for hand-foot syndrome.
DRUGAcetaminophen
Analgesic for hand foot syndrome as needed.
DRUGLevothyroxine
Replacement therapy for participants with increases in thyroid-stimulating hormone.
DRUGWarfarin
2mg daily for prophylaxis of thrombosis.
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to 120 Years
Healthy volunteers
No
Inclusion 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 OR * creatinine clearance greater than or equal to 60 mL/min for patients with creatinine levels above institutional normal * QT corrected for heart rate (QTc) \<480 msec (with Bazett's correction) in screening electrocardiogram. * The following groups of patients are eligible after consultation with a cardiologist and at the Coordinating Center PI's discretion, provided they have New York Heart Association Class II (NYHA) cardiac function on baseline echocardiogram (ECHO): * those with a history of Class II heart failure who are asymptomatic on treatment * those with prior anthracycline exposure greater than a cumulative dose of 350 mg/m(2) * those who have received central thoracic radiation that included the heart in the radiotherapy port. * Patients must have blood pressure (BP) no greater than 140 millimeters of mercury (mmHg) (systolic) and 90 mmHg (diastolic) for eligibility. Initiation or adjustment of BP medication is permitted prior to study entry provided that the BP reading prior to enrollment is no greater than 140/90 mmHg. * Left ventricular ejection fraction (LVEF) greater than or equal to institutional lower limit of normal. * Because sunitinib is metabolized primarily by the cytochrome P450 3A4 (CYP3A4) liver enzyme, strong CYP3A4 inhibitors are not permitted within 7 days before and during the study, and strong CYP3A4 inducers are not permitted within 12 days before and during the study. A list of drugs that may interact with the cytochrome P450 system is included in Appendix C. Every effort should be made to switch patients taking such agents or substances to other medications 1 week prior to starting therapy, particularly patients with brain metastases who are taking enzyme- inducing anticonvulsant agents (Appendix D). Patients who require potent CYP3A4 inducers or inhibitors and cannot switch medications must have their case reviewed by the Coordinating Center PI and may be enrolled only after discussion with and agreement from the Coordinating Center PI. Current clinical studies with cediranib have not found clinically significant effects on cediranib pharmacokinetic (PK) with co-administration of CYP3A4 inducers or inhibitors. Eligibility of patients receiving any medications or substances known to affect or with the potential to affect the activity or pharmacokinetics (PK) of cediranib will be determined following review of their case by the Coordinating Center PI. * Both study agents have been shown to terminate fetal development in the rat, as expected for a process dependent on VEGF signaling. For this reason, women of childbearing potential must have a negative pregnancy test prior to study entry. Women of child-bearing potential and men must agree to use two reliable forms of contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 2 months following study drug discontinuation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. * Patients who are nursing infants: because there is an unknown but potential risk for adverse events (AEs) in nursing infants secondary to treatment of the mother with study agents, breastfeeding should be discontinued if the mother is treated with the study agents. * Ability to understand and the willingness to sign a written informed consent document. * Patients must be able to swallow whole tablets and capsules.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part I: Objective Response Rate (ORR) of Single-agent Cediranib in Participants With Advanced Alveolar Soft Part Sarcoma (ASPS) | Time on treatment (an average of 497 days or 16 months) | 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. |
| Part I: Objective Response Rate (ORR) of Single-agent Sunitinib in Participants With Advanced Alveolar Soft Part Sarcoma (ASPS) | Time on treatment (an average of 497 days or 16 months) | 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. |
| Part II: Objective Response Rate (ORR) of Sunitinib in Participants Who Progress on the Cediranib Arm During Part I | Time on treatment (an average of 497 days or 16 months) | 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. |
| Part II: Objective Response Rate (ORR) of Cediranib in Participants Who Progress on the Sunitinib Arm During Part I | Time on treatment (an average of 497 days or 16 months) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Pharmacokinetic analysis was performed on blood samples from participants on cediranib (both upfront therapy and following cross-over). Human plasma samples were analyzed using a validated liquid chromatography-mass spectrometry (LC-MS) method and the maximum observed analyte concentration in plasma will be reported. No sampling or analysis will be done for participants receiving sunitinib. |
| 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 | 24-week PFS is defined as the probability of participants remaining alive and progression-free at 24 weeks after the start of treatment. Progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) and is defined as the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. |
| 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 | Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORAlice P Chen, M.D.
National Cancer Institute (NCI)
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AZD2171 (Cediranib) 30 mg Treatment assignment code 1. Part I: Participants will be randomized to receive cediranib (30 mg) orally, once a day, in 28-day cycles. Part I is a two-stage design in which 10 participants are initially enrolled in each arm. If 0 or 1 of the 10 participants has a clinical response, then no further participants will be accrued. That treatment arm will be closed to the accrual of new participants and the crossover of participants who progressed on the other agent. If 2 or more the first 10 participants have a response, then accrual would continue until a total of 22 participants have enrolled in that arm. Part II: At the time of disease progression (documented by Response Evaluation Criteria in Solid Tumors (RECIST v1), participants will cross over to the other treatment arm after a 2-week wash-out period (unless the other arm has been closed due to inadequate activity or unacceptable toxicity). | 7 |
| AZD2171 (Cediranib) 30 mg Followed by Sunitinib Malate 37.5 mg Treatment assignment code 1 followed by treatment assignment code 2. Part I: Participants will be randomized to receive cediranib (30 mg) or sunitinib malate (37.5 mg) orally, once a day, in 28-day cycles. Part I is a two-stage design in which 10 participants are initially enrolled in each arm. If 0 or 1 of the 10 participants has a clinical response, then no further participants will be accrued. That treatment arm will be closed to the accrual of new participants and the crossover of participants who progressed on the other agent. If 2 or more the first 10 patients have a response, then accrual would continue until a total of 22 participants have enrolled in that arm. Part II: At the time of disease progression (documented by Response Evaluation Criteria in Solid Tumors (RECIST v1), participants will cross over to the other treatment arm after a 2-week wash-out period (unless the other arm has been closed due to inadequate activity or unacceptable toxicity). | 9 |
| Sunitinib Malate 37.5 mg Treatment assignment code 2. Part I: Participants will be randomized to receive sunitinib malate (37.5 mg) orally, once a day, in 28-day cycles. Part I is a two-stage design in which 10 participants are initially enrolled in each arm. If 0 or 1 of the 10 participants has a clinical response, then no further participants will be accrued. That treatment arm will be closed to the accrual of new participants and the crossover of participants who progressed on the other agent. If 2 or more the first 10 participants have a response, then accrual would continue until a total of 22 participants have enrolled in that arm. Part II: At the time of disease progression (documented by Response Evaluation Criteria in Solid Tumors (RECIST v1), patients will cross over to the other treatment arm after a 2-week wash-out period (unless the other arm has been closed due to inadequate activity or unacceptable toxicity). | 5 |
| Sunitinib Malate 37.5 mg Followed by AZD2171 (Cediranib) 30 mg Treatment assignment code 2 followed by treatment assignment code 1. Part I: Participants will be randomized to receive cediranib (30 mg) or sunitinib malate (37.5 mg) orally, once a day, in 28-day cycles. Part I is a two-stage design in which 10 patients are initially enrolled in each arm. If 0 or 1 of the 10 participants has a clinical response, then no further participants will be accrued. That treatment arm will be closed to the accrual of new participants and the crossover of participants who progressed on the other agent. If 2 or more the first 10 participants have a response, then accrual would continue until a total of 22 participants have enrolled in that arm. Part II: At the time of disease progression (documented by Response Evaluation Criteria in Solid Tumors (RECIST v1), participants will cross over to the other treatment arm after a 2-week wash-out period (unless the other arm has been closed due to inadequate activity or unacceptable toxicity). | 13 |
| Total | 34 |
Baseline characteristics
| Characteristic | AZD2171 (Cediranib) 30 mg | Total | Sunitinib Malate 37.5 mg Followed by AZD2171 (Cediranib) 30 mg | Sunitinib Malate 37.5 mg | AZD2171 (Cediranib) 30 mg Followed by Sunitinib Malate 37.5 mg |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 31 Participants | 11 Participants | 5 Participants | 8 Participants |
| Age, Continuous | 26.67 years STANDARD_DEVIATION 11.03 | 29.64 years STANDARD_DEVIATION 12.09 | 32.87 years STANDARD_DEVIATION 13.72 | 30.88 years STANDARD_DEVIATION 17.74 | 26.6 years STANDARD_DEVIATION 6.03 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 3 Participants | 0 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 31 Participants | 13 Participants | 4 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 6 Participants | 3 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 10 Participants | 4 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 16 Participants | 5 Participants | 4 Participants | 1 Participants |
| Region of Enrollment United States | 7 participants | 34 participants | 13 participants | 5 participants | 9 participants |
| Sex: Female, Male Female | 2 Participants | 7 Participants | 2 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 5 Participants | 27 Participants | 11 Participants | 4 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 1 / 27 |
| other Total, other adverse events | 28 / 29 | 26 / 27 |
| serious Total, serious adverse events | 7 / 29 | 7 / 27 |
Outcome results
Primary
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 frame: Time on treatment (an average of 497 days or 16 months)
Population: A total of 10/34 participants were analyzed: 10/13 participants who received cediranib in Part II were analyzed (3 participants were not evaluable for response).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AZD2171 (Cediranib) 30 mg | Part II: Objective Response Rate (ORR) of Cediranib in Participants Who Progress on the Sunitinib Arm During Part I | Complete Response | 0 Participants |
| AZD2171 (Cediranib) 30 mg | Part II: Objective Response Rate (ORR) of Cediranib in Participants Who Progress on the Sunitinib Arm During Part I | Partial Response | 1 Participants |
Primary
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 frame: Time on treatment (an average of 497 days or 16 months)
Population: A total of 9/34 participants were analyzed: 9/9 participants who received sunitinib in Part II were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AZD2171 (Cediranib) 30 mg | Part II: Objective Response Rate (ORR) of Sunitinib in Participants Who Progress on the Cediranib Arm During Part I | Complete Response | 0 Participants |
| AZD2171 (Cediranib) 30 mg | Part II: Objective Response Rate (ORR) of Sunitinib in Participants Who Progress on the Cediranib Arm During Part I | Partial Response | 0 Participants |
Primary
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 frame: Time on treatment (an average of 497 days or 16 months)
Population: A total of 15/34 participants were analyzed: 15/16 participants who received cediranib in Part I were analyzed (1 participant was not evaluable for response).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AZD2171 (Cediranib) 30 mg | Part I: Objective Response Rate (ORR) of Single-agent Cediranib in Participants With Advanced Alveolar Soft Part Sarcoma (ASPS) | Complete Response | 0 Participants |
| AZD2171 (Cediranib) 30 mg | Part I: Objective Response Rate (ORR) of Single-agent Cediranib in Participants With Advanced Alveolar Soft Part Sarcoma (ASPS) | Partial Response | 0 Participants |
| AZD2171 (Cediranib) 30 mg Followed by Sunitinib Malate 37.5 mg | Part I: Objective Response Rate (ORR) of Single-agent Cediranib in Participants With Advanced Alveolar Soft Part Sarcoma (ASPS) | Complete Response | 0 Participants |
| AZD2171 (Cediranib) 30 mg Followed by Sunitinib Malate 37.5 mg | Part I: Objective Response Rate (ORR) of Single-agent Cediranib in Participants With Advanced Alveolar Soft Part Sarcoma (ASPS) | Partial Response | 1 Participants |
Primary
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 frame: Time on treatment (an average of 497 days or 16 months)
Population: A total of 14/34 participants were analyzed: 14/18 participants who received sunitinib in Part I were analyzed (4 participants who received sunitinib were not evaluable for response.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AZD2171 (Cediranib) 30 mg | Part I: Objective Response Rate (ORR) of Single-agent Sunitinib in Participants With Advanced Alveolar Soft Part Sarcoma (ASPS) | Complete Response | 0 Participants |
| AZD2171 (Cediranib) 30 mg | Part I: Objective Response Rate (ORR) of Single-agent Sunitinib in Participants With Advanced Alveolar Soft Part Sarcoma (ASPS) | Partial Response | 0 Participants |
| AZD2171 (Cediranib) 30 mg Followed by Sunitinib Malate 37.5 mg | Part I: Objective Response Rate (ORR) of Single-agent Sunitinib in Participants With Advanced Alveolar Soft Part Sarcoma (ASPS) | Complete Response | 0 Participants |
| AZD2171 (Cediranib) 30 mg Followed by Sunitinib Malate 37.5 mg | Part I: Objective Response Rate (ORR) of Single-agent Sunitinib in Participants With Advanced Alveolar Soft Part Sarcoma (ASPS) | Partial Response | 1 Participants |
Secondary
Maximum Observed Plasma Concentration of Cediranib
Pharmacokinetic analysis was performed on blood samples from participants on cediranib (both upfront therapy and following cross-over). Human plasma samples were analyzed using a validated liquid chromatography-mass spectrometry (LC-MS) method and the maximum observed analyte concentration in plasma will be reported. No sampling or analysis will be done for participants receiving sunitinib.
Time frame: 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)
Population: A total of 15/34 participants were analyzed: 15/29 participants who received cediranib in either Part I or Part II were analyzed.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| AZD2171 (Cediranib) 30 mg | Maximum Observed Plasma Concentration of Cediranib | 108 Nanomolar |
| AZD2171 (Cediranib) 30 mg Followed by Sunitinib Malate 37.5 mg | Maximum Observed Plasma Concentration of Cediranib | 115 Nanomolar |
| Sunitinib Malate 37.5 mg Followed by AZD2171 (Cediranib) 30 mg | Maximum Observed Plasma Concentration of Cediranib | 126 Nanomolar |
Secondary
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0).
Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Time frame: Date treatment consent signed to date off study, an average of 523 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AZD2171 (Cediranib) 30 mg | Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). | 7 Participants |
| AZD2171 (Cediranib) 30 mg Followed by Sunitinib Malate 37.5 mg | Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). | 9 Participants |
| Sunitinib Malate 37.5 mg Followed by AZD2171 (Cediranib) 30 mg | Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). | 4 Participants |
| Sunitinib Malate 37.5 mg Followed by AZD2171 (Cediranib) 30 mg | Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). | 13 Participants |
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
24-week PFS is defined as the probability of participants remaining alive and progression-free at 24 weeks after the start of treatment. Progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) and is defined as the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Time frame: 24 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AZD2171 (Cediranib) 30 mg | 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 Percentage of participants |
| AZD2171 (Cediranib) 30 mg Followed by Sunitinib Malate 37.5 mg | 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 Percentage of participants |
| Sunitinib Malate 37.5 mg Followed by AZD2171 (Cediranib) 30 mg | 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 | 50.0 Percentage of participants |
| Sunitinib Malate 37.5 mg Followed by AZD2171 (Cediranib) 30 mg | 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 | 50.0 Percentage of participants |
Other Pre-specified
Best Overall Response During Part I for Participants Who Were Not Newly Diagnosed
Best overall response is the best response recorded from the start of the treatment until disease progression/recurrence. Response was assessed 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. Progression is the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Stable disease is neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease.
Time frame: Time on treatment (an average of 497 days or 16 months)
Population: A total of 11/34 participants were analyzed: of the 14 participants who were not newly diagnosed, 2 participants randomized to receive sunitinib and 1 participant randomized to receive cediranib in Part I were not evaluable for response, leaving only 11 reportable participants.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AZD2171 (Cediranib) 30 mg | Best Overall Response During Part I for Participants Who Were Not Newly Diagnosed | Complete Response | 0 Participants |
| AZD2171 (Cediranib) 30 mg | Best Overall Response During Part I for Participants Who Were Not Newly Diagnosed | Partial Response | 0 Participants |
| AZD2171 (Cediranib) 30 mg | Best Overall Response During Part I for Participants Who Were Not Newly Diagnosed | Stable Disease | 0 Participants |
| AZD2171 (Cediranib) 30 mg | Best Overall Response During Part I for Participants Who Were Not Newly Diagnosed | Progressive Disease | 0 Participants |
| AZD2171 (Cediranib) 30 mg Followed by Sunitinib Malate 37.5 mg | Best Overall Response During Part I for Participants Who Were Not Newly Diagnosed | Partial Response | 0 Participants |
| AZD2171 (Cediranib) 30 mg Followed by Sunitinib Malate 37.5 mg | Best Overall Response During Part I for Participants Who Were Not Newly Diagnosed | Stable Disease | 3 Participants |
| AZD2171 (Cediranib) 30 mg Followed by Sunitinib Malate 37.5 mg | Best Overall Response During Part I for Participants Who Were Not Newly Diagnosed | Progressive Disease | 0 Participants |
| AZD2171 (Cediranib) 30 mg Followed by Sunitinib Malate 37.5 mg | Best Overall Response During Part I for Participants Who Were Not Newly Diagnosed | Complete Response | 0 Participants |
| Sunitinib Malate 37.5 mg Followed by AZD2171 (Cediranib) 30 mg | Best Overall Response During Part I for Participants Who Were Not Newly Diagnosed | Stable Disease | 1 Participants |
| Sunitinib Malate 37.5 mg Followed by AZD2171 (Cediranib) 30 mg | Best Overall Response During Part I for Participants Who Were Not Newly Diagnosed | Partial Response | 0 Participants |
| Sunitinib Malate 37.5 mg Followed by AZD2171 (Cediranib) 30 mg | Best Overall Response During Part I for Participants Who Were Not Newly Diagnosed | Progressive Disease | 0 Participants |
| Sunitinib Malate 37.5 mg Followed by AZD2171 (Cediranib) 30 mg | Best Overall Response During Part I for Participants Who Were Not Newly Diagnosed | Complete Response | 0 Participants |
| Sunitinib Malate 37.5 mg Followed by AZD2171 (Cediranib) 30 mg | Best Overall Response During Part I for Participants Who Were Not Newly Diagnosed | Progressive Disease | 1 Participants |
| Sunitinib Malate 37.5 mg Followed by AZD2171 (Cediranib) 30 mg | Best Overall Response During Part I for Participants Who Were Not Newly Diagnosed | Partial Response | 1 Participants |
| Sunitinib Malate 37.5 mg Followed by AZD2171 (Cediranib) 30 mg | Best Overall Response During Part I for Participants Who Were Not Newly Diagnosed | Complete Response | 0 Participants |
| Sunitinib Malate 37.5 mg Followed by AZD2171 (Cediranib) 30 mg | Best Overall Response During Part I for Participants Who Were Not Newly Diagnosed | Stable Disease | 5 Participants |
Other Pre-specified
Best Overall Response During Part II for Participants Who Were Not Newly Diagnosed
Best overall response is the best response recorded from the start of the treatment until disease progression/recurrence. Response was assessed 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. Progression is the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Stable disease is neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease.
Time frame: Time on treatment (an average of 497 days or 16 months)
Population: A total of 10/34 participants were analyzed: of the 11 participants who were not newly diagnosed and participated in Part II of the trial, 1 participant (who was randomized to receive sunitinib in Part I and then crossed over to receive cediranib in Part II) was not evaluable for response, leaving only 10 reportable participants.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AZD2171 (Cediranib) 30 mg | Best Overall Response During Part II for Participants Who Were Not Newly Diagnosed | Progressive Disease | 0 Participants |
| AZD2171 (Cediranib) 30 mg | Best Overall Response During Part II for Participants Who Were Not Newly Diagnosed | Partial Response | 0 Participants |
| AZD2171 (Cediranib) 30 mg | Best Overall Response During Part II for Participants Who Were Not Newly Diagnosed | Not Scanned | 0 Participants |
| AZD2171 (Cediranib) 30 mg | Best Overall Response During Part II for Participants Who Were Not Newly Diagnosed | Stable Disease | 0 Participants |
| AZD2171 (Cediranib) 30 mg | Best Overall Response During Part II for Participants Who Were Not Newly Diagnosed | Complete Response | 0 Participants |
| AZD2171 (Cediranib) 30 mg Followed by Sunitinib Malate 37.5 mg | Best Overall Response During Part II for Participants Who Were Not Newly Diagnosed | Stable Disease | 2 Participants |
| AZD2171 (Cediranib) 30 mg Followed by Sunitinib Malate 37.5 mg | Best Overall Response During Part II for Participants Who Were Not Newly Diagnosed | Progressive Disease | 1 Participants |
| AZD2171 (Cediranib) 30 mg Followed by Sunitinib Malate 37.5 mg | Best Overall Response During Part II for Participants Who Were Not Newly Diagnosed | Not Scanned | 0 Participants |
| AZD2171 (Cediranib) 30 mg Followed by Sunitinib Malate 37.5 mg | Best Overall Response During Part II for Participants Who Were Not Newly Diagnosed | Partial Response | 0 Participants |
| AZD2171 (Cediranib) 30 mg Followed by Sunitinib Malate 37.5 mg | Best Overall Response During Part II for Participants Who Were Not Newly Diagnosed | Complete Response | 0 Participants |
| Sunitinib Malate 37.5 mg Followed by AZD2171 (Cediranib) 30 mg | Best Overall Response During Part II for Participants Who Were Not Newly Diagnosed | Stable Disease | 0 Participants |
| Sunitinib Malate 37.5 mg Followed by AZD2171 (Cediranib) 30 mg | Best Overall Response During Part II for Participants Who Were Not Newly Diagnosed | Complete Response | 0 Participants |
| Sunitinib Malate 37.5 mg Followed by AZD2171 (Cediranib) 30 mg | Best Overall Response During Part II for Participants Who Were Not Newly Diagnosed | Partial Response | 0 Participants |
| Sunitinib Malate 37.5 mg Followed by AZD2171 (Cediranib) 30 mg | Best Overall Response During Part II for Participants Who Were Not Newly Diagnosed | Progressive Disease | 0 Participants |
| Sunitinib Malate 37.5 mg Followed by AZD2171 (Cediranib) 30 mg | Best Overall Response During Part II for Participants Who Were Not Newly Diagnosed | Not Scanned | 0 Participants |
| Sunitinib Malate 37.5 mg Followed by AZD2171 (Cediranib) 30 mg | Best Overall Response During Part II for Participants Who Were Not Newly Diagnosed | Progressive Disease | 2 Participants |
| Sunitinib Malate 37.5 mg Followed by AZD2171 (Cediranib) 30 mg | Best Overall Response During Part II for Participants Who Were Not Newly Diagnosed | Partial Response | 1 Participants |
| Sunitinib Malate 37.5 mg Followed by AZD2171 (Cediranib) 30 mg | Best Overall Response During Part II for Participants Who Were Not Newly Diagnosed | Complete Response | 0 Participants |
| Sunitinib Malate 37.5 mg Followed by AZD2171 (Cediranib) 30 mg | Best Overall Response During Part II for Participants Who Were Not Newly Diagnosed | Stable Disease | 3 Participants |
| Sunitinib Malate 37.5 mg Followed by AZD2171 (Cediranib) 30 mg | Best Overall Response During Part II for Participants Who Were Not Newly Diagnosed | Not Scanned | 1 Participants |
Other Pre-specified
Percentage of Participants With Progression-free Survival (PFS) at 24 Weeks During Part I for Participants Who Were Not Newly Diagnosed
24-week PFS is defined as the probability of patients remaining alive and progression-free at 24 weeks after the start of treatment. Progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) and is defined as the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Time frame: 24 weeks
Population: A total of 14/34 participants were analyzed. 20 participants not analyzed were newly diagnosed. The outcome is for non-newly diagnosed participants only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AZD2171 (Cediranib) 30 mg | Percentage of Participants With Progression-free Survival (PFS) at 24 Weeks During Part I for Participants Who Were Not Newly Diagnosed | 50.0 Percentage of participants |
| AZD2171 (Cediranib) 30 mg Followed by Sunitinib Malate 37.5 mg | Percentage of Participants With Progression-free Survival (PFS) at 24 Weeks During Part I for Participants Who Were Not Newly Diagnosed | 50.0 Percentage of participants |
| Sunitinib Malate 37.5 mg Followed by AZD2171 (Cediranib) 30 mg | Percentage of Participants With Progression-free Survival (PFS) at 24 Weeks During Part I for Participants Who Were Not Newly Diagnosed | 40.0 Percentage of participants |
| Sunitinib Malate 37.5 mg Followed by AZD2171 (Cediranib) 30 mg | Percentage of Participants With Progression-free Survival (PFS) at 24 Weeks During Part I for Participants Who Were Not Newly Diagnosed | 40.0 Percentage of participants |
Other Pre-specified
Percentage of Participants With Progression-free Survival (PFS) at 24 Weeks During Part II for Participants Who Were Not Newly Diagnosed
24-week PFS is defined as the probability of patients remaining alive and progression-free at 24 weeks after the start of treatment. Progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) and is defined as the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Time frame: 24 weeks
Population: 11/34 participants were analyzed: all 11 participants who were not newly diagnosed and participated in Part II of the trial were analyzed. 20 participants were not analyzed as they were newly diagnosed and this outcome is for non-newly diagnosed participants only. In addition, 3 participants who were not newly diagnosed did not participate in Part II of the trial, leaving 11 participants who were not newly diagnosed and who participated in Part II of the trial, for whom this outcome is reported.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AZD2171 (Cediranib) 30 mg Followed by Sunitinib Malate 37.5 mg | Percentage of Participants With Progression-free Survival (PFS) at 24 Weeks During Part II for Participants Who Were Not Newly Diagnosed | 33.3 percentage of participants |
| Sunitinib Malate 37.5 mg Followed by AZD2171 (Cediranib) 30 mg | Percentage of Participants With Progression-free Survival (PFS) at 24 Weeks During Part II for Participants Who Were Not Newly Diagnosed | 57.1 percentage of participants |