Dermatofibrosarcomas of DARIER FERRAND(DFSP)Phase 2DFSP-PAZONCT01059656
Phase II Pazopanib Study in Advanced Dermatofibrosarcomas
A Phase 2 study testing Pazopanib in people with Dermatofibrosarcomas of DARIER FERRAND(DFSP), run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Dermatofibrosarcomas of DARIER FERRAND(DFSP)
- What is being tested?
- Pazopanib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteFrance
- Study dates
- Jul 2010to Apr 2014
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 25Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
France1 site
Hôpital Saint-Louis - Service de Dermatologie (Pole POPS)
Paris, 75010
About this study
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.
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.
Read the 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 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.
- Being tested
- Pazopanib
- Keywords
- Dermatofibrosarcoma, Pazopanib¨, Phase II
- Medical subject headings
- Dermatofibrosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PazopanibDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 1:Pazopanib | Experimental | Pazopanib 800mg/j Receives: Drug: Pazopanib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Decrease of at least 30% of the biggest diameter measured clinically at 6 months preceded by clinical response
Measured: at 3 months
Secondary outcomes (7)
For measure of tumour volume : Measure of radiologic response (" MULTIBARETTE " MDCT scanner) using RECIST criteria and OMS (WHO)
Measured: at 3 months
For measure of tumour volume : Measure of the volume of the tumour (" MULTIBARETTE " MDCT scanner) in each centre
Measured: 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)
Measured: at 3 months
Prognostic factors of tumoral response : Semi-quantitative measure of apoptosis on surgical piece and of senescence
Measured: at inclusion, M1, M3 and M6
Expression of the phosphorylated form of the receptors of PDGFB and VEGF and of the MAPK.
Measured: at inclusion, M1, M3 and M6
Prognostic factors of tumoral response :Clinical and biologic safety Common Terminology Criteria forAdverse Events v3.0 (CTCAE)
Measured: at every visit except M0
Prognostic factors of tumoral response :Evaluation of QOL, EORTC QLQ-C30
Measured: M0, M3, M6, M9, M12, M15 and M18
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2010 (estimated)
- Study startJul 2010
- Primary completionApr 2014
- Study completionApr 2014
Why it stopped: Decision of Study Principal Investigator
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Dermatofibrosarcomas of DARIER FERRAND(DFSP)Studies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- Celeste LEBBE, MD-PhD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01059656
- Sponsor's protocol ID
- P090402
- Other IDs
- 2009-014096-46, 2009
- Acronym
- DFSP-PAZO
- Status last verified
- Jun 2016
- First submitted
- 28 Jan 2010
- Last updated
- 1 Jul 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 32956651
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01059656
- Acronym / sponsor ID
- DFSP-PAZO / P090402
- Keywords
- Dermatofibrosarcoma, Pazopanib¨, Phase II
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Decision of Study Principal Investigator
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- GlaxoSmithKline
- Study start
- Jul 2010
- Primary completion
- Apr 2014 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 1 Feb 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1:Pazopanib | Experimental | Drug: PazopanibPazopanib 800mg/j |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (25 listed)
- 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 <
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PazopanibAdministration 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. | Drug | 1:Pazopanib |
Primary outcome
Decrease of at least 30% of the biggest diameter measured clinically at 6 months preceded by clinical response
Time frame: at 3 months
7 secondary outcomes
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
Results and safety
The study was stopped early (reason given: Decision of Study Principal Investigator). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2016.
- Derived from this study: PubMed 32956651Delyon 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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Celeste LEBBE, MD-PhD principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pazopanib in people with Dermatofibrosarcomas of DARIER FERRAND(DFSP), run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 1 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Decision of Study Principal Investigator). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Decrease of at least 30% of the biggest diameter measured clinically at 6 months preceded by clinical response (time frame: at 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01059656, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jul 2016; AzTrials last refreshed its copy on 30 Oct 2026.