Dermatofibrosarcomas of DARIER FERRAND(DFSP) Clinical Trial
— DFSP-PAZOOfficial 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.
| Verified date | June 2016 |
| Source | Assistance Publique - Hôpitaux de Paris |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | France: Ministry of Health |
| Study type | Interventional |
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.
| Status | Terminated |
| Enrollment | 23 |
| Est. completion date | April 2014 |
| Est. primary completion date | April 2014 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 20 Years and older |
| Eligibility |
Inclusion Criteria: - Primitive unresectable DFSP, locally advanced (potentially mutilating surgery), or in relapse or transformed. - Histologic confirmation of the Darier-FERRAND tumour (transformed types will be accepted provided a previous caryotype confirming the translocation (17,22) - Age > or equal to 20 years - Signed informed consent - Appropriate contraception - No evolutive tumoural disease except baso-cellular carcinoma - Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1. Exclusion Criteria: - Patient refusal to participate - Age < 20 years - Pregnant or lactating women - Other evolutive tumour disease except baso-cellular carcinoma - Haematologic abnormalities:Hemoglobin < 9g/dl, PNN < - 1500/mm3, Platelets <100000/mm3 - AST and ALT > 2N - Bilirubin > 1.5N - Creatinin > 1.5mg/dL or creatinin clearance <30ml/mn - Proteinuria >1g/24h - Serum albumin< 2.5g/dL - Hepatitis B, C and/or HIV known Infection - Treatment interfering with pazopanib - Major surgical procedure, open biopsy, or significant traumatic injury within 4 weeks prior to beginning therapy, or anticipation of the need for a major surgical procedure during the course of the study. - Clinically significant gastrointestinal abnormalities including, but not limited to:Malabsorption syndromeDisease significantly affecting gastrointestinal function or major resection of the stomach or small bowel that could affect the absorption of study drug.Active peptic ulcer diseaseInflammatory bowel diseaseUlcerative colitis, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis or other gastrointestinal condition increasing the risk of perforation.History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment· Presence of active or uncontrolled infection. - Evidence of active bleeding or bleeding diathesis. - History of any one or more of the following cardiovascular conditions within the past 6 months:Coronary/peripheral artery bypass graft, cardiac angioplasty or stenting.Myocardial infarction.Severe/unstable angina pectoris.Symptomatic peripheral vascular disease pulmonary embolism, thromboembolic event, cerebrovascular accident or transient ischemic attack.Class III or IV congestive heart failure, as defined by the New York Heart Association - Cardiovascular disease with NYHA > II - Poorly controlled hypertension (defined as a systolic blood pressure (SBP) of =140 mmHg or diastolic blood pressure (DBP) =90 mmHg. - Following abnormalities on ECG : Q wave, ischemia, QTc > 450 msec, atrioventricular block 2 or 3, atrial fibrillation - Therapeutic anticoagulation treatment. - Chronic daily treatment with aspirin (= 100 mg/day) or non-steroidal anti-inflammatory agents known to inhibit platelet function. Treatment with dipyridamole, ticlopidine, clopidogrel and/or cilostazol is also not allowed.. Concurrent treatment with an investigational agent or participation in another clinical trial. - Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib. - Taken by the order treatment anti cancerous concomitants within 4 weeks previous inclusion - Radiotherapy on the hurt within 3 months previous inclusion |
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| France | Hôpital Saint-Louis - Service de Dermatologie (Pole POPS) | Paris |
| Lead Sponsor | Collaborator |
|---|---|
| Assistance Publique - Hôpitaux de Paris | GlaxoSmithKline |
France,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Decrease of at least 30% of the biggest diameter measured clinically at 6 months preceded by clinical response | at 3 months | Yes | |
| Secondary | For measure of tumour volume : Measure of radiologic response (" MULTIBARETTE " MDCT scanner) using RECIST criteria and OMS (WHO) | at 3 months | Yes | |
| Secondary | For measure of tumour volume : Measure of the volume of the tumour (" MULTIBARETTE " MDCT scanner) in each centre | at 3 months | Yes | |
| Secondary | For measure of tumour volume : Research of translocation COL1A1-PDGFB by FISH (paraffin) and caryotype on fresh tissue (centralisation in F PEDEUTOUR laboratory, Nice) | at 3 months | Yes | |
| Secondary | Prognostic factors of tumoral response : Semi-quantitative measure of apoptosis on surgical piece and of senescence | at inclusion, M1, M3 and M6 | Yes | |
| Secondary | Expression of the phosphorylated form of the receptors of PDGFB and VEGF and of the MAPK. | at inclusion, M1, M3 and M6 | Yes | |
| Secondary | Prognostic factors of tumoral response :Clinical and biologic safety Common Terminology Criteria forAdverse Events v3.0 (CTCAE) | at every visit except M0 | Yes | |
| Secondary | Prognostic factors of tumoral response :Evaluation of QOL, EORTC QLQ-C30 | M0, M3, M6, M9, M12, M15 and M18 | Yes |