Phase II trial of PF-03084014 in adults with desmoid tumors/aggressive fibromatosis.

9516 Background: Background: Aggressive fibromatosis/desmoid tumors (AF/DT) are rare tumors with loco regional spreading. Few options are available when local treatments have failed. Although cytotoxic agents, hormonal treatment have been reported to induced responses and tumor control in some patients, only few prospective phase II trials have been reported in the literature. Recently, antitumor activity of imatinib in AF/DT was reported. We report a phase II trial of imatinib in AF/DT after failure of local treatment options. Methods: Pts ≥ 18 years with advanced AF/DT from all sites in whom neither surgery nor radiotherapy was possible were eligible. The principal inclusion criterias were: disease not amenable to surgery and/or radiation with curative intent, systemic pre-treatments allowed and presence of a measurable lesion with evidence of progression. Imatinib was given at the dose of 400 mg/d and increased to 800 mg/d if progression. Primary endpoint was the rate of progression free at 3 months. A two stages Simon‘s optimal design was used with p0=10%, p1=30%, α=0.05 and 90% power. 18 pts were scheduled to be recruited in the first stage for a total of 35 evaluable pts. Results: Between 09/2004 and 10/2005, 40 pts were included in 15 centers. The median age was 40 years (range 20–72) with 26% males. Primary sites were extra abdominal, mesenteric, abdominal wall in 79, 15, and 6% respectively. 15% patients had not been operated previously and 17% undergone radiotherapy. Prior systemic treatments were: NSAID, hormonal therapy or chemotherapy in 34, 46 and 23%, respectively. Median treatment duration was 4 months (range 0–12). No G4 toxicity was reported. Toxicities (G1–3) were notified for 30 pts including asthenias (70%), nauseas (53%), diarrheas, oedema (40%). G3 toxicities were abdominal pain (10%), rash, nausea, vomiting and asthenia (7%). At 3 months, 22 pts (55%) were evaluable with 1 CR, 17 SD and 4PD. As of December 2005, 7 of the 40 pts had progressed. After progression, dose was stopped in 2 pts and increased to 800mg in 5 pts with 2 tumor control following dose-escalation. Conclusions: Imatinib induces prolonged disease stabilization in the majority of evaluable patients with AF/DT in whom no local treatment option was available. [Table: see text]

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Imatinib for progressive and recurrent aggressive fibromatosis (desmoid tumors): an FNCLCC/French Sarcoma Group phase II trial with a long-term follow-up

Annals of Oncology ◽

10.1093/annonc/mdq341 ◽

2011 ◽

Vol 22 (2) ◽

pp. 452-457 ◽

Cited By ~ 119

Author(s):

N. Penel ◽

A. Le Cesne ◽

B.N. Bui ◽

D. Perol ◽

E.G. Brain ◽

...

Keyword(s):

Phase Ii ◽

Phase Ii Trial ◽

Aggressive Fibromatosis ◽

Desmoid Tumors ◽

Long Term Follow Up

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1624MO Weekly nab-paclitaxel for progressive or symptomatic desmoid tumors: A multicenter single arm phase II trial from the Spanish Group for Research on Sarcoma (GEIS)

Annals of Oncology ◽

10.1016/j.annonc.2020.08.1850 ◽

2020 ◽

Vol 31 ◽

pp. S975

Author(s):

J. Martin Broto ◽

N. Hindi ◽

A. Redondo ◽

J.M. Morales ◽

D. Marcilla ◽

...

Keyword(s):

Phase Ii ◽

Phase Ii Trial ◽

Desmoid Tumors

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A SARC phase II multicenter trial of imatinib mesylate (IM) in patients with aggressive fibromatosis

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.9515 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 9515-9515 ◽

Cited By ~ 4

Author(s):

R. Chugh ◽

R. G. Maki ◽

D. G. Thomas ◽

D. Reinke ◽

J. K. Wathen ◽

...

Keyword(s):

Phase Ii ◽

Primary Endpoint ◽

Phase Ii Trial ◽

Case Reports ◽

Point Mutations ◽

Case Series ◽

Aggressive Fibromatosis ◽

Median Number ◽

Fresh Tissue ◽

Maximum Change

9515 Background: Aggressive fibromatosis (desmoid tumors, AF) are uncommon, locally aggressive, connective tissue neoplasms. Existing literature on systemic treatment of AF is sparse and consists mostly of case reports and small case-series. Based on previous observation of regression of AF treated with IM and tumoral expression of IM targets, SARC (Sarcoma Alliance for Research through Collaboration) included the treatment of AF onto a multi-institution phase II trial of IM in sarcoma. Here we report early clinical and laboratory results of the AF group. Methods: Eligible patients had histologically proven AF, unresectable or difficult to resect without considerable functional impairment. Patients were treated with IM 300 mg po BID (BSA≥1.5m2). The primary endpoint was complete (CR) or partial response(PR) at two months or stable disease (SD) or better at four months. Tumor DNA was extracted from available formalin fixed paraffin embedded tissue specimens and analyzed via allelic PCR and genomic DNA sequence analysis for specific point mutations in PDGFRα exons 12/14/18, PDGFRβ exons 12/18, KIT exons 9/11/13/17, and bRAF. Results: 51 patients were enrolled from 10/02 to 12/05 at 5 institutions, with 45 patients currently evaluable. The median age is 37 (range 14–67), and median number of prior therapies is 1 (range 0–3). 36 patients (80%) reached the primary endpoint of CR/PR at 2 months or SD or better at 4 months. The median time to treatment failure is 6.8 months (95% C.I. 5.8–17.1). Thus far, the maximum change in the largest dimension of the tumor ranged from a 21% increase to a 45% decrease. In 22 available tumor specimens, deletions within PDGFRαE12 and E18 were noted in 1 and 3 patients, respectively, while a wildtype genotype was found in other regions. Conclusions: IM has activity in AF, the mechanism of which remains unclear. While this is the largest reported phase II trial of AF, further improvement in evaluating clinical efficacy in this disease is clearly necessary. We plan an analysis of the maximum change in largest tumor dimension for each patient, which will be particularly beneficial in AF as responses often occur late. We have not as yet identified a laboratory predictor of clinical benefit. Further investigation of other potential targets in fresh tissue is warranted. [Table: see text]

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Whole-genome and Transcriptome Sequencing Identified NOTCH2 and HES1 as Potential Markers of Response to Imatinib in Desmoid Tumor (Aggressive Fibromatosis): A Phase II Trial Study

Cancer Research and Treatment ◽

10.4143/crt.2021.1194 ◽

2022 ◽

Author(s):

Joonha Kwon ◽

Jun Hyeong Lee ◽

Young Han Lee ◽

Jeeyun Lee ◽

Jin-Hee Ahn ◽

...

Keyword(s):

Phase Ii ◽

Desmoid Tumor ◽

Transcriptome Sequencing ◽

Phase Ii Trial ◽

Aggressive Fibromatosis ◽

Whole Genome

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Activity of imatinib mesylate in desmoid tumors: Interim analysis of a Sarcoma Alliance for Research thru Collaboration (SARC) phase II trial

Journal of Clinical Oncology ◽

10.1200/jco.2004.22.90140.9013 ◽

2004 ◽

Vol 22 (14_suppl) ◽

pp. 9013-9013 ◽

Cited By ~ 2

Author(s):

L. H. Baker ◽

K. Wathen ◽

R. Chugh ◽

D. Thomas ◽

P. F. Thall ◽

...

Keyword(s):

Imatinib Mesylate ◽

Phase Ii ◽

Interim Analysis ◽

Phase Ii Trial ◽

Desmoid Tumors

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Updated outcome with long-term follow-up of imatinib for the treatment of progressive or recurrent aggressive fibromatosis (desmoid tumor): A FNCLCC/ French Sarcoma Group phase II trial

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.10518 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 10518-10518 ◽

Cited By ~ 1

Author(s):

A. Dufresne ◽

N. Penel ◽

S. Salas ◽

A. Le Cesne ◽

D. Perol ◽

...

Keyword(s):

Overall Survival ◽

Phase Ii ◽

Progressive Disease ◽

Phase Ii Trial ◽

Progression Free Survival ◽

Aggressive Fibromatosis ◽

Disease Rate ◽

Free Survival ◽

Number Of Patients

10518 Background: We present updated results from a previously reported phase II trial assessing clinical efficacy of imatinib in progressive or recurrent aggressive fibromatosis (Fayette et al. ASCO 2007) Methods: Patients with aggressive fibromatosis not amenable to radiotherapy or non-mutilating surgery were eligible and received imatinib 400mg daily (increased to 800mg daily in case of progression) up to 1 year then stopped. The primary end point was non-progressive disease rate at 3 months. Independent radiological committee reviewed responses. The number of patients was calculated according to a optimal 2-stages design. Results: Forty patients were included between September 2004 and October 2005 in 15 centers. The median follow up is 33 months [95% CI: 32–35]. Toxicity of imatinib is similar to that previously reported. At 3 months, the nonprogression rate was 91% [95% CI: 77–96] with 1 (2%) complete and 3 (8%) partial confirmed responses observed. The non progression rates at 6, 9, and 12 months were 80%, 69% and 66% respectively. The median time to progression was 9.5 months. The 2-year progression-free survival (PFS) was 55%. No plateau was observed. The 2-year-overall survival was 95%. Two patients with mesenteric aggressive fibromatosis died from progressive disease. In multivariate analysis including clinical factors, only previous radiotherapy was associated with reduced progression free survival. None of the biological factors tested using IHC on TMA (PDGFR α, PDGFR β, β catenin, c-kit, E cadherine, MCSFR, cycline D1 and Erk) were found correlated to response, progression free or overall survival. Conclusions: With a 2.8 years median follow up, this is the largest study which confirms the high efficacy of imatinib (400 mg daily) in patients presenting with aggressive fibromatosis failing local treatment and with documented evidence of progressive disease before imatinib treatment. [Table: see text]

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