Ignite Creation Date:
2024-05-05 @ 10:11 PM
Last Modification Date:
2024-10-26 @ 10:15 AM
Study NCT ID:
NCT01059656
Status:
TERMINATED
Last Update Posted:
2016-07-01
First Post:
2010-01-28
Brief Title:
Phase II Pazopanib Study in Advanced Dermatofibrosarcomas
Sponsor:
Assistance Publique - Hôpitaux de Paris
Organization:
Assistance Publique - Hôpitaux de Paris
Study Overview
Official Title:
A Phase IIa Open Multicenter Trial of Treatment With Pazopanib Multi Tyrosine Kinase Inhibitor in Dermatofibrosarcomas DFSP Unresectable Locally Advanced Potentially Mutilating Surgery Primary or Relapsing Transformed or Not
Status:
TERMINATED
Status Verified Date:
2016-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Decision of Study Principal Investigator
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
DFSP-PAZO
Brief Summary:
In relation to the activation of PDGF-mediated signalization due to the fusion gene COL1A1-PDGFb in DFSP imatinib 800mgday has shown activity in advanced DFSP and has became the reference treatment option for these patients Yet the activity observed does not allow for a downstaging compatible with successful resection in a number of patients and does not prevent subsequent tumour progression in case of residual tumourPazopanib in relation to 1 its multi tyrosine kinase inhibiting activity VEGFR-1 VEGFR-2 VEGFR-3 PDGFR-α PDGFR-β and c-kit with IC50 values of 10 30 47 71 84 and 74 nM respectively involving in particular PDGFR and VEGFR which has been shown to be activated in DFSP 2 its antitumour activity in sarcomas patients and 3 its acceptable safety profile is a logical candidate for therapeutic trials in DFSP both in patients not expected to derive a sufficient benefit from imatinib and in patients failing imatinib mesylate Moreover using quantitative RT-PCR and immunohistochemistry we have recently demonstrated high levels of VEGF and VEGFR2 expression in dermatofibrosarcoma
Detailed Description:
Dermatofibrosarcoma protuberance DFSP is a rare soft tissue sarcoma of intermediate malignant potential Treatment relies on a wide local excision with negative margin and with frequent need of reconstructive surgery A translocation between chromosomes 17 and 22 that places the platelet-derived growth factor-B PDGFB under the control of the collagen 1A1 promoter is present in 90 of the cases leading to an up regulation of PDGF-β expression and activation of the tyrosinase kinase PDGFRβ Imatinib mesylate has been approved in unresectable and metastatic DFSP due to its activity on PDGFR This study will evaluate the benefit of pazopanib a multikinase inhibitor in advanced DFSP Administration of pazopanib per os 800mg qd during 6 months until stable response according to primary endpoint and for a period of study not exceeding one yearIn case of progression evaluated according to the primary endpoint after a period of treatment superior to one month or in the absence of response at 3 months the patient will be withdrawn from study in order to get alternative therapeutics These patients will be considered as failures for analysis After a 6-month treatment period and reaching a stable response treatment continuation decision will be based on the operability of patients
Administration of pazopanib per os 800mg qd during 6 months until stable response according to primary endpoint with 3 monthly successive examinations and for a period of study not exceeding 18 monthsIn case of progression evaluated according to the primary endpoint after a period of treatment superior to one month or in the absence of response at 3 months the patient will be withdrawn from study in order to get alternative therapeutics These patients will be considered as failures for analysis After a 6-month treatment period and reaching a stable response treatment continuation decision will be based on the operability of patients Statistical analysis The trial has been planned using a one-stage design Fleming TR Et al Analysis of the main endpoint will rely on a one-sided binomial test comparing the observed response rate to the expected response rate under the null hypothesis The type I error rate is fixed at 0025For the main endpoint a point estimate and a two-sided 90 confidence interval will be presented which will be consistent with the one-sided test at a 0025 level For secondary endpoints point estimates and 95 confidence intervals will be presentedWe intend to estimate the probability of tumour size reduction of at least 30 The sample size was calculated by FLEMMING method Ho will be defined by a RR 20 decrease in tumour size of at least 30 H1 response rate 26 patients must be included in order to demonstrate an efficacy as defined by a RR50 with a 90 power and alfa 25 one side
Administration of pazopanib per os 800mg qd during 6 months until stable response according to primary endpoint with 3 monthly successive examinations and for a period of study not exceeding 18 monthsIn case of progression evaluated according to the primary endpoint after a period of treatment superior to one month or in the absence of response at 3 months the patient will be withdrawn from study in order to get alternative therapeutics These patients will be considered as failures for analysis After a 6-month treatment period and reaching a stable response treatment continuation decision will be based on the operability of patients Statistical analysis The trial has been planned using a one-stage design Fleming TR Et al Analysis of the main endpoint will rely on a one-sided binomial test comparing the observed response rate to the expected response rate under the null hypothesis The type I error rate is fixed at 0025For the main endpoint a point estimate and a two-sided 90 confidence interval will be presented which will be consistent with the one-sided test at a 0025 level For secondary endpoints point estimates and 95 confidence intervals will be presentedWe intend to estimate the probability of tumour size reduction of at least 30 The sample size was calculated by FLEMMING method Ho will be defined by a RR 20 decrease in tumour size of at least 30 H1 response rate 26 patients must be included in order to demonstrate an efficacy as defined by a RR50 with a 90 power and alfa 25 one side
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 |
|---|---|---|---|
| 2009-014096-46 | EUDRACT_NUMBER | None | None |