Ignite Creation Date:
2024-05-06 @ 12:57 AM
Last Modification Date:
2024-10-26 @ 10:56 AM
Study NCT ID:
NCT01692496
Status:
COMPLETED
Last Update Posted:
2020-07-23
First Post:
2012-09-14
Brief Title:
Activity and Tolerability of Pazopanib in Advanced andor Metastatic Liposarcoma A Phase II Clinical Trial
Sponsor:
Grupo Espanol de Investigacion en Sarcomas
Organization:
Grupo Espanol de Investigacion en Sarcomas
Study Overview
Official Title:
Phase II Clinical Trial of Pazopanib to Evaluate the Activity and Tolerability in Patients With Advanced andor Metastatic Liposarcoma Who Have Relapsed Following Standard Therapies or for Whom no Standard Therapy Exists
Status:
COMPLETED
Status Verified Date:
2020-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Soft tissue and bone sarcomas are rare malignant tumors which encompasses a large family of more than 50 histologically distinct tumor subtypes all of which share a putative mesenchymal origin In the case of soft tissue sarcomas STS surgical excision is the mainstay of treatment but despite curative surgery around half of patients develop distant metastases and die from disease Few therapeutic approaches are currently available to patients with unresectable locally advanced or metastatic STS and only anthracyclines ifosfamide and trabectedin have shown activity with response rates of 20-40 in previously untreated patients Recent and ongoing trials have investigated a variety of combination chemotherapeutic regimens variously employing ifosfamide doxorubicin gemcitabine temozolomide vincristine cisplatin and dacarbazine among others as well as targeted therapies which in some cases have yielded improvements in response rate but which have had little impact on survival No other medical option is currently available and the median survival of patients with soft-tissue sarcoma with non-resectable metastases is around 12-15 months and approximately 8 months after second line chemotherapy
Liposarcomas are STS which account for at least 20 of all STS in adults They can be further classified into 3 histologically and biologically different subtypes well-differentiated liposarcomadedifferentiated liposarcoma ALT-WD myxoid or round cell liposarcoma and pleomorphic liposarcoma
ALT-WD liposarcomas are locally aggressive rarely metastasizing tumors characterized by ring or giant marker chromosomes on the cytogenetic analysis and by amplification of the 12q13-21 region on Fluorescence In Situ Hybridization FISH MDM2 CDK4 and HMGIC They account for about 40 iv of liposarcomas with a 5 year Overall survival OS around 80 In a series of WDDD treated with several regimens response rate was 125 OS 15 months and median PFS 36 months95 confidence interval CI 33-59 Mixoid round cell liposarcoma accounts for 45-50 of all liposarcomas They tend to metastasize to unusual soft tissue and bone locations High histologic grade with more than 5 of round cell component is associated with a 5-year OS of 50 approximately They are characterized by t2316q13-14p11 which leads to the fusion of CHOP and TLS genes Pleomorphic liposarcoma accounts for approximately 5-10 of all liposarcomas characterized by high grade features with frequent and early lung metastasis and cytogenetically by high chromosome counts and complex structural rearrangements
VEGF is expressed in many STS in which increased expression is associated with higher grade and worse prognosis
Pazopanib is an oral angiogenesis inhibitor that targets mainly VEGFR PDGFR and c-kit Recently the results of a phase II trial of pazopanib in STS have been published It was a four-cohort 2-stages study The liposarcoma stratum was closed after the first stage because of a PFS at 12 weeks of 17 3 out of 17 patients did not progressed after 12 weeks After central pathologic review 2 other patients initially classified as other STS were found to have liposarcoma with stable disease at 12 weeks 519 26 PFS12w thus fulfilling criteria for cohort expansion Phase II study had been completed and in phase III study patients with liposarcomas were excluded so therefore data on the liposarcoma cohort are inconclusive
Furthermore the positive results of the phase III study PALETTE have been recently communicated encouraging this treatment in other sarcomas progression-free survival PFS per independent review was significantly prolonged with pazopanib median 46 vs 15 months HR031 95 CI 024-040 P00001 The interim analysis for overall survival shows a statistically non-significant improvement of pazopanib vs placebo median 119 vs 104 months HR083 95 CI 062-109
Soluble factors associated with efficacy and toxicity of pazopanib in these patients had been also reported Decreases in VEGFR2 and increase in PlGF were both associated with toxicity HTA and TSH elevation and poorer prognosis
Liposarcomas are STS which account for at least 20 of all STS in adults They can be further classified into 3 histologically and biologically different subtypes well-differentiated liposarcomadedifferentiated liposarcoma ALT-WD myxoid or round cell liposarcoma and pleomorphic liposarcoma
ALT-WD liposarcomas are locally aggressive rarely metastasizing tumors characterized by ring or giant marker chromosomes on the cytogenetic analysis and by amplification of the 12q13-21 region on Fluorescence In Situ Hybridization FISH MDM2 CDK4 and HMGIC They account for about 40 iv of liposarcomas with a 5 year Overall survival OS around 80 In a series of WDDD treated with several regimens response rate was 125 OS 15 months and median PFS 36 months95 confidence interval CI 33-59 Mixoid round cell liposarcoma accounts for 45-50 of all liposarcomas They tend to metastasize to unusual soft tissue and bone locations High histologic grade with more than 5 of round cell component is associated with a 5-year OS of 50 approximately They are characterized by t2316q13-14p11 which leads to the fusion of CHOP and TLS genes Pleomorphic liposarcoma accounts for approximately 5-10 of all liposarcomas characterized by high grade features with frequent and early lung metastasis and cytogenetically by high chromosome counts and complex structural rearrangements
VEGF is expressed in many STS in which increased expression is associated with higher grade and worse prognosis
Pazopanib is an oral angiogenesis inhibitor that targets mainly VEGFR PDGFR and c-kit Recently the results of a phase II trial of pazopanib in STS have been published It was a four-cohort 2-stages study The liposarcoma stratum was closed after the first stage because of a PFS at 12 weeks of 17 3 out of 17 patients did not progressed after 12 weeks After central pathologic review 2 other patients initially classified as other STS were found to have liposarcoma with stable disease at 12 weeks 519 26 PFS12w thus fulfilling criteria for cohort expansion Phase II study had been completed and in phase III study patients with liposarcomas were excluded so therefore data on the liposarcoma cohort are inconclusive
Furthermore the positive results of the phase III study PALETTE have been recently communicated encouraging this treatment in other sarcomas progression-free survival PFS per independent review was significantly prolonged with pazopanib median 46 vs 15 months HR031 95 CI 024-040 P00001 The interim analysis for overall survival shows a statistically non-significant improvement of pazopanib vs placebo median 119 vs 104 months HR083 95 CI 062-109
Soluble factors associated with efficacy and toxicity of pazopanib in these patients had been also reported Decreases in VEGFR2 and increase in PlGF were both associated with toxicity HTA and TSH elevation and poorer prognosis
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2012-002745-38 | EUDRACT_NUMBER | None | None |