A Phase 2 interventional study of Pazopanib in Dermatofibrosarcomas of DARIER FERRAND(DFSP), sponsored by Assistance Publique - Hôpitaux de Paris. Terminated at 1 site in France. Open to participants aged 20 Years and older. Per ClinicalTrials.gov, last updated 2016-07-01.
Sponsored by Assistance Publique - Hôpitaux de Paris · Phase 2, Interventional, and Treatment
In relation to the activation of PDGF-mediated signalization due to the fusion gene COL1A1-PDGFb in DFSP, imatinib (800mg/day) 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 tumour.Pazopanib 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.
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 year.In 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 months.In 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 0.025.For 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 0.025 level. For secondary endpoints, point estimates and 95% confidence intervals will be presented.We 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 RR≥50%, with a 90% power and alfa 2.5% one side.
28 studies on the registry are indexed under Dermatofibrosarcoma; 9 are open to participants now.
This study's enrollment of 23 is below the median of 35 across 26 interventional studies indexed under Dermatofibrosarcoma.
Browse Dermatofibrosarcoma studies →Assistance Publique - Hôpitaux de Paris is the lead sponsor of 3,576 studies on the registry; 1,028 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Pazopanib 800mg/j
Drug: Pazopanib
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 months.
Decrease of at least 30% of the biggest diameter measured clinically at 6 months preceded by clinical response
Time frame: at 3 months
For measure of tumour volume : Measure of radiologic response (" MULTIBARETTE " MDCT scanner) using RECIST criteria and OMS (WHO)
Time frame: at 3 months
For measure of tumour volume : Measure of the volume of the tumour (" MULTIBARETTE " MDCT scanner) in each centre
Time frame: at 3 months
For measure of tumour volume : Research of translocation COL1A1-PDGFB by FISH (paraffin) and caryotype on fresh tissue (centralisation in F PEDEUTOUR laboratory, Nice)
Time frame: at 3 months
Prognostic factors of tumoral response : Semi-quantitative measure of apoptosis on surgical piece and of senescence
Time frame: at inclusion, M1, M3 and M6
Expression of the phosphorylated form of the receptors of PDGFB and VEGF and of the MAPK.
Time frame: at inclusion, M1, M3 and M6
Prognostic factors of tumoral response :Clinical and biologic safety Common Terminology Criteria forAdverse Events v3.0 (CTCAE)
Time frame: at every visit except M0
Prognostic factors of tumoral response :Evaluation of QOL, EORTC QLQ-C30
Time frame: M0, M3, M6, M9, M12, M15 and M18
The record gives a start of Jul 2010, a primary completion of Apr 2014 and a completion of Apr 2014. It does not say whether these dates are actual or estimated.
How these figures are worked out, and which studies are left out of them.
This study is terminated, as verified in Jun 2016. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Pazopanib
Assistance Publique - Hôpitaux de Paris →