Phase II Pazopanib Study in Advanced Dermatofibrosarcomas

NCT01059656 | Terminated Phase 2

• 2 other identifiers: P0904022009-014096-46
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Dermatofibrosarcomas of DARIER FERRAND(DFSP)

Keywords

Dermatofibrosarcoma; Pazopanib¨; Phase II

Outcome Measures

Primary Outcomes (1)

• Decrease of at least 30% of the biggest diameter measured clinically at 6 months preceded by clinical response

  at 3 months

Secondary Outcomes (7)

• For measure of tumour volume : Measure of radiologic response (" MULTIBARETTE " MDCT scanner) using RECIST criteria and OMS (WHO)

  at 3 months

• For measure of tumour volume : Measure of the volume of the tumour (" MULTIBARETTE " MDCT scanner) in each centre

  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)

  at 3 months

• Prognostic factors of tumoral response : Semi-quantitative measure of apoptosis on surgical piece and of senescence

  at inclusion, M1, M3 and M6

• Expression of the phosphorylated form of the receptors of PDGFB and VEGF and of the MAPK.

  at inclusion, M1, M3 and M6

Study Arms (1)

1:Pazopanib

EXPERIMENTAL

Pazopanib 800mg/j

Drug: Pazopanib

Interventions

Pazopanib DRUG

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.

1:Pazopanib

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 \<
• /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.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Hôpital Saint-Louis - Service de Dermatologie (Pole POPS)

Paris, 75010, France

Location

Related Publications (1)

• Delyon J, Porcher R, Battistella M, Meyer N, Adamski H, Bertucci F, Guillot B, Jouary T, Leccia MT, Dalac S, Mortier L, Ghrieb Z, Da Meda L, Vicaut E, Pedeutour F, Mourah S, Lebbe C. A Multicenter Phase II Study of Pazopanib in Patients with Unresectable Dermatofibrosarcoma Protuberans. J Invest Dermatol. 2021 Apr;141(4):761-769.e2. doi: 10.1016/j.jid.2020.06.039. Epub 2020 Sep 18.

  PMID: 32956651 DERIVED

MeSH Terms

Conditions

Dermatofibrosarcoma

Interventions

pazopanib

Condition Hierarchy (Ancestors)

Fibrosarcoma; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Study Officials

• Celeste LEBBE, MD-PhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2010
• First Posted: February 1, 2010
• Study Start: July 1, 2010
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: July 1, 2016

Record last verified: 2016-06

Locations

FR (1)