Sunitinib or Cediranib for Alveolar Soft Part Sarcoma
- Conditions
- Sarcoma, Alveolar Soft Part
- Interventions
- Other: ProchlorperazineOther: PromethazineOther: BenzodiazepineOther: FilgrastimOther: SargramostimOther: LomotilOther: LoperamideOther: Vitamin B6Other: Aquaphor
- Registration Number
- NCT01391962
- Lead Sponsor
- National Cancer Institute (NCI)
- 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 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 RECIST 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:
* 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 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 RECIST 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 (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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 34
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Part I - Cediranib (30 mg) or Sunitinib Malate (37.5 mg) Orally Cediranib Patients will be randomized to receive cediranib (30 mg) or sunitinib malate (37.5 mg) orally, once a day in 28-day cycles. Part I - Cediranib (30 mg) or Sunitinib Malate (37.5 mg) Orally Prochlorperazine Patients will be randomized to receive cediranib (30 mg) or sunitinib malate (37.5 mg) orally, once a day in 28-day cycles. Part I - Cediranib (30 mg) or Sunitinib Malate (37.5 mg) Orally Promethazine Patients will be randomized to receive cediranib (30 mg) or sunitinib malate (37.5 mg) orally, once a day in 28-day cycles. Part I - Cediranib (30 mg) or Sunitinib Malate (37.5 mg) Orally Benzodiazepine Patients will be randomized to receive cediranib (30 mg) or sunitinib malate (37.5 mg) orally, once a day in 28-day cycles. Part I - Cediranib (30 mg) or Sunitinib Malate (37.5 mg) Orally Filgrastim Patients will be randomized to receive cediranib (30 mg) or sunitinib malate (37.5 mg) orally, once a day in 28-day cycles. Part I - Cediranib (30 mg) or Sunitinib Malate (37.5 mg) Orally Sargramostim Patients will be randomized to receive cediranib (30 mg) or sunitinib malate (37.5 mg) orally, once a day in 28-day cycles. Part I - Cediranib (30 mg) or Sunitinib Malate (37.5 mg) Orally Lomotil Patients will be randomized to receive cediranib (30 mg) or sunitinib malate (37.5 mg) orally, once a day in 28-day cycles. Part I - Cediranib (30 mg) or Sunitinib Malate (37.5 mg) Orally Loperamide Patients will be randomized to receive cediranib (30 mg) or sunitinib malate (37.5 mg) orally, once a day in 28-day cycles. Part I - Cediranib (30 mg) or Sunitinib Malate (37.5 mg) Orally Vitamin B6 Patients will be randomized to receive cediranib (30 mg) or sunitinib malate (37.5 mg) orally, once a day in 28-day cycles. Part I - Cediranib (30 mg) or Sunitinib Malate (37.5 mg) Orally Aquaphor Patients will be randomized to receive cediranib (30 mg) or sunitinib malate (37.5 mg) orally, once a day in 28-day cycles. Part I - Cediranib (30 mg) or Sunitinib Malate (37.5 mg) Orally Acetaminophen 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 - Cross Over Cediranib At the time of disease progression, patients will cross over to the other treatment arm after a 2-week wash-out period. Part II - Cross Over Sunitinib At the time of disease progression, patients will cross over to the other treatment arm after a 2-week wash-out period. Part II - Cross Over Prochlorperazine At the time of disease progression, patients will cross over to the other treatment arm after a 2-week wash-out period. Part II - Cross Over Promethazine At the time of disease progression, patients will cross over to the other treatment arm after a 2-week wash-out period. Part II - Cross Over Benzodiazepine At the time of disease progression, patients will cross over to the other treatment arm after a 2-week wash-out period. Part II - Cross Over Filgrastim At the time of disease progression, patients will cross over to the other treatment arm after a 2-week wash-out period. Part II - Cross Over Sargramostim At the time of disease progression, patients will cross over to the other treatment arm after a 2-week wash-out period. Part II - Cross Over Lomotil At the time of disease progression, patients will cross over to the other treatment arm after a 2-week wash-out period. Part II - Cross Over Loperamide At the time of disease progression, patients will cross over to the other treatment arm after a 2-week wash-out period. Part II - Cross Over Vitamin B6 At the time of disease progression, patients will cross over to the other treatment arm after a 2-week wash-out period. Part II - Cross Over Aquaphor At the time of disease progression, patients will cross over to the other treatment arm after a 2-week wash-out period. Part II - Cross Over Acetaminophen At the time of disease progression, patients will cross over to the other treatment arm after a 2-week wash-out period. Part I - Cediranib (30 mg) or Sunitinib Malate (37.5 mg) Orally Warfarin Patients will be randomized to receive cediranib (30 mg) or sunitinib malate (37.5 mg) orally, once a day in 28-day cycles. Part I - Cediranib (30 mg) or Sunitinib Malate (37.5 mg) Orally Sunitinib Patients will be randomized to receive cediranib (30 mg) or sunitinib malate (37.5 mg) orally, once a day in 28-day cycles. Part I - Cediranib (30 mg) or Sunitinib Malate (37.5 mg) Orally Levothyroxine 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 - Cross Over Levothyroxine At the time of disease progression, patients will cross over to the other treatment arm after a 2-week wash-out period. Part II - Cross Over Warfarin At the time of disease progression, patients will cross over to the other treatment arm after a 2-week wash-out period.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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.
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States