Imatinib for the treatment of aggressive fibromatosis (desmoid tumors) failing local treatment. A phase II trial of the French Sarcoma Group

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 9516-9516 ◽  
Author(s):  
N. Penel ◽  
A. Le Cesne ◽  
B. Bui ◽  
M. Tubiana-Hulin ◽  
C. Guillemet ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Local Treatment ◽  
Aggressive Fibromatosis ◽  
Cytotoxic Agents ◽  
Tumor Control ◽  
Desmoid Tumors ◽  
Phase Ii Trials ◽  
Curative Intent ◽  
Systemic Treatments

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]

Imatinib for the treatment of aggressive fibromatosis/desmoid tumors (AF/DT) failing local treatment: updated outcome and predictive factors for progression free survival. A FNCLCC French Sarcoma Group-GETO study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10062-10062
Author(s):  
J. Fayette ◽  
A. Dufresne ◽  
N. Penel ◽  
A. Le Cesne ◽  
B. Bui Nguyen ◽  
...  
Keyword(s):  
Predictive Factors ◽  
Local Treatment ◽  
Progression Free Survival ◽  
Aggressive Fibromatosis ◽  
Tissue Microarrays ◽  
Long Term Results ◽  
Tumor Control ◽  
Curative Surgery ◽  
Kit Mutation ◽  
Systemic Treatments

10062 Background: The optimal treatment of AF/DT failing local treatments is not defined. We report long term results and predictive factors for response to imatinib in AF/DT. Methods: Pts =18 years with advanced AF/DT from all sites in whom neither curative surgery nor radiotherapy (RT) was possible were eligible. Imatinib was given at the dose of 400mg/d (and increased to 800 mg/d if progression) during 1 year then stopped. Primary endpoint was the progression free at 3 months. A two stages Simon‘s optimal design was used with p0=10%, p1=30%, a=0.05 and 90% power (18 pts first stage, total of 35 evaluable pts). Predictive factors were investigated using tissue-microarrays (TMA) and KIT mutation analysis. Results: Between 09/2004 and 10/2005, 40 pts were included in 15 centers. Median age was 40 (range 20–72) with 30% males. Primary sites were extra abdominal, mesenteric, and abdominal wall in 69, 18, and 13% of pts respectively. 23% had received RT. Prior systemic treatments were: NSAID, hormonotherapy or chemotherapy (CT) in 33%, 45% and 20% of pts respectively. Median treatment duration of imatinib is 9 months (range 0.8–13.8). G4 and G3 toxicities were notified in 0 and 17 patients (42.5%) respectively: rash (4 pts), abdominal pain (3 pts), and vomiting (3 pts). 38 pts (95%) are evaluable at 3 months, with 1 (3%) CR, 3 (8%) RP, 31 (82%) SD and 3 (8%) PD. With a median follow-up of 13.8 months, 13 of the 40 pts had progressed. PFS at one year is 71% and 1 patient died (PD). 8 patients received an increased dose of imatinib upon progression under a 400mg/d dose: 3 reprogressed and 5 achieved tumor stabilization during 5+, 6+, 8+ months. PFS was correlated to weight or to previous CT, but not to gender, Gardner, age, PS, size, site. Using TMA, the expression of PDGFR β and a β catenin, E-cadherine, cyclinD1, M-CSFR, estrogen receptor β, ERK, phospho-Akt-Ser473, phospho-MEK1–2 were investigated. None of the CycD1+ tumors have progressed so far. 3 mutations of KIT exon 10 were detected in 10 patients tested. All achieved tumor control. Conclusions: Imatinib induces prolonged disease stabilization in the majority of evaluable patients with AF/DT. Prognostic factors were identified. [Table: see text]

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

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 10563-10563 ◽  
Author(s):  
Shivaani Kummar ◽  
Khanh Tu Do ◽  
Geraldine Helen O'Sullivan Coyne ◽  
Baris Turkbey ◽  
Paul S. Meltzer ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Aggressive Fibromatosis ◽  
Desmoid Tumors

A review of 565 phase II trial abstracts from ASCO 2005: Design characteristics of contemporary trials evaluating cytotoxic versus non-cytotoxic regimens

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6569-6569
Author(s):  
C. Elser ◽  
G. Pond ◽  
E. Chen ◽  
L. Siu
Keyword(s):  
North America ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Phase Ii Trial ◽  
Median Number ◽  
Cytotoxic Agents ◽  
Targeted Agents ◽  
Time To Event ◽  
Phase Ii Trials ◽  
Number Of Patients

6569 Background: New phase II trial designs have been proposed to accommodate the non-cytotoxic nature of molecularly targeted agents. In particular, the use of alternative endpoints and controls has been suggested. The objectives of this survey are to review the designs of contemporary phase II trials, to compare trials of cytotoxic versus non-cytotoxic regimens, and to identify predictors of acceptance for presentation. Methods: Abstracts of phase II trials of systemic anticancer therapy published in the 2005 ASCO Proceedings were hand searched. The trial context, type of intervention, trial design, endpoints, and completeness of reporting were assessed. Results: Our search yielded 565 abstracts: 72% were multi-center, 44% North American, 25% clearly identified as industry-sponsored, the median number of patients was 44 (range 8–346). Only 83% explicitly reported the study phase, 29% the primary endpoint, 11% the number of stages, and 5% the statistical design. For design properties, 16% used multiple arms and 6% used enrichment. Of trials reporting the primary endpoint, 48% used radiological or marker response and 22% time-to-event endpoints. The median number of endpoints was 4 (range 1–8). Non- cytotoxic regimens, which included targeted agents, hormone- or immunotherapy, constituted 22% of the trials reviewed, purely cytotoxic regimens 60%, the remaining 18% contained combinations of both. Trials of non-cytotoxic and combination regimens were more likely to report the primary endpoint (p=0.02), use time-to-event endpoints (p=0.006), have multiple arms, use enrichment, be conducted in North America, be industry-sponsored, and be accepted for oral or poster presentation (all p<0.001). Other predictors of publication type in multivariate analysis were multi-centricity, higher number of patients, industry involvement, and being conducted in North America (all p<0.05). Conclusions: Design properties of contemporary phase II trials of non-cytotoxic agents differ from trials of cytotoxic chemotherapy, and are more likely to be accepted for presentation at ASCO. Proposed new trial designs start to be more widely adopted. Most abstracts incompletely report design properties. No significant financial relationships to disclose.

Consolidative radiotherapy for metastatic urothelial bladder cancer patients without progression and with no more than three residual metastatic lesions following first line systemic therapy: A prospective randomized comparative phase II trial (BLAD RAD01/GETUG-AFU V07).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS4588-TPS4588
Author(s):  
Jonathan Khalifa ◽  
Damien Pouessel ◽  
Mathieu Roumiguie ◽  
Paul Sargos ◽  
Genevieve Loos ◽  
...  
Keyword(s):  
Phase Ii ◽  
Systemic Therapy ◽  
Phase Ii Trial ◽  
Local Treatment ◽  
Standard Of Care ◽  
Urothelial Bladder Cancer ◽  
First Line ◽  
Metastatic Lesions ◽  
Urothelial Bladder ◽  
Consolidative Radiotherapy

TPS4588 Background: Consolidative local treatment of the primary tumor in the treatment of metastatic malignancies has shown promising results in several types of tumors, mostly relying on the seed-and-soil theory. Furthermore, the local treatment of the residual metastases following systemic treatment is a promising approach, in part due to the high incidence of progression at prior sites of disease in patients who had initially responded to chemotherapy. To date, no prospective data exists on such consolidative approach in metastatic urothelial bladder cancer (mUBC). The phase II trial BLAD-RAD01 GETUG-AFU V07 was designed to investigate the role of local consolidative radiotherapy in patients with limited mUBC and without progression following the initial phase of first-line systemic therapy. Methods: This is a phase II, multicenter, randomized open-label and comparative study. Patients with mUBC (excluding brain and liver metastases), without progression following standard first-line systemic therapy according to RECIST v1.1, and with no more than 3 residual metastatic lesions on 18FDG-PET scanner and/or contrast-enhanced CT-scanner are eligible for the study. After the completion of systemic treatment, an estimated 130 patients will be randomized in a 1:1 ratio between consolidative local treatment (pelvic radiotherapy +/- previous transurethal resection of bladder tumor, associated with stereotactic body radiotherapy (SBRT) to the residual metastases) plus standard of care (arm B) and standard of care only (arm A). Stratification is performed based upon: the center, the ECOG performance status, the administration of immunotherapy or not, the number of residual metastatic lesions and the imaging modality for assessment of the number of residual lesions. To date, standard of care for this population is maintenance treatment with avelumab. Radiotherapy regimens consist in conventionally fractionated (64Gy in 32 fractions) or hypofractionated (55Gy in 20 fractions) irradiation of the bladder, optional pelvic nodes irradiation, and 3 to 5 fractions of 6 to 18 Gy in SBRT for metastases, depending on the location. The main objective is to detect an increase in 20-month overall survival rate following chemotherapy from 50% (based upon the JAVELIN 100 trial) to 66%; this corresponds to a hazard ratio of 0.6. A total of 83 events are necessary for 85% power to detect this difference if it is true using a one-sided logrank test at the 10% of significance. Target difference, type I and II error rates are relaxed and compatibles with recommendations for comparative phase II trials. Key secondary endpoints are progression free survival, safety and quality of life. To date, one patient has been enrolled and eight centers are open for accrual. Clinical trial information: NCT04428554.

scholarly journals 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)

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

Surveillance or Metastasis-Directed Therapy for Oligometastatic Prostate Cancer Recurrence: A Prospective, Randomized, Multicenter Phase II Trial

2018 ◽  
Vol 36 (5) ◽  
pp. 446-453 ◽  
Author(s):  
Piet Ost ◽  
Dries Reynders ◽  
Karel Decaestecker ◽  
Valérie Fonteyne ◽  
Nicolaas Lumen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Specific Antigen ◽  
Phase Iii ◽  
Curative Intent ◽  
Free Survival ◽  
Local Progression ◽  
Randomized Phase Ii

Purpose Retrospective studies suggest that metastasis-directed therapy (MDT) for oligorecurrent prostate cancer (PCa) improves progression-free survival. We aimed to assess the benefit of MDT in a randomized phase II trial. Patients and Methods In this multicenter, randomized, phase II study, patients with asymptomatic PCa were eligible if they had had a biochemical recurrence after primary PCa treatment with curative intent, three or fewer extracranial metastatic lesions on choline positron emission tomography–computed tomography, and serum testosterone levels > 50 ng/mL. Patients were randomly assigned (1:1) to either surveillance or MDT of all detected lesions (surgery or stereotactic body radiotherapy). Surveillance was performed with prostate-specific antigen (PSA) follow-up every 3 months, with repeated imaging at PSA progression or clinical suspicion for progression. Random assignment was balanced dynamically on the basis of two factors: PSA doubling time (≤ 3 v > 3 months) and nodal versus non-nodal metastases. The primary end point was androgen deprivation therapy (ADT)–free survival. ADT was started at symptomatic progression, progression to more than three metastases, or local progression of known metastases. Results Between August 2012 and August 2015, 62 patients were enrolled. At a median follow-up time of 3 years (interquartile range, 2.3-3.75 years), the median ADT-free survival was 13 months (80% CI, 12 to 17 months) for the surveillance group and 21 months (80% CI, 14 to 29 months) for the MDT group (hazard ratio, 0.60 [80% CI, 0.40 to 0.90]; log-rank P = .11). Quality of life was similar between arms at baseline and remained comparable at 3-month and 1-year follow-up. Six patients developed grade 1 toxicity in the MDT arm. No grade 2 to 5 toxicity was observed. Conclusion ADT-free survival was longer with MDT than with surveillance alone for oligorecurrent PCa, suggesting that MDT should be explored further in phase III trials.

A phase II trial of irinotecan, 5-fluorouracil and leucovorin in patients with previously untreated advanced colorectal cancer (CRC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14599-14599
Author(s):  
N. Lee ◽  
S. Bae ◽  
S. Lee ◽  
D. Kim ◽  
K. Kim ◽  
...  
Keyword(s):  
Continuous Infusion ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Objective Response ◽  
Tumor Control ◽  
Ecog Performance Status ◽  
Grade 3 ◽  
Ecog Ps

14599 Background: We prospectively conducted a phase II trial to test the efficacy and safety of irinotecan, 5-fluorouracil and leucovorin (FOLFIRI) regimens for the first-line treatment of previously untreated patients with recurrent or metastatic advanced CRC. Methods: Thirty-four previously untreated patients with advanced CRC were enrolled in this study from June 2001 to December 2006. Eligible patients had histologically confirmed adenocarcinoma, no prior systemic therapy in palliative setting, ECOG PS = 2, adequate organ function, written informed consent and at least one measurable disease. The patients received either irinotecan 180 mg/m2 on day 1 with a LV bolus of 200 mg/m2 and a FU bolus of 400 mg/m2, and this was followed by a FU continuous infusion of 600 mg/m2 on day 1 and day 2 (the classic FOLFIRI regimen), or they were treated with a LV bolus of 400 mg/m2 and a FU bolus of 400 mg/m2 followed by a FU continuous infusion of 2,400 mg/m2 for 46 hours (the simplified FOLFIRI regimen), and these treatments were repeated every 2 weeks until disease progression. Results: There were 13 females and 21 males with median age of 54 years (range: 41–79). The most common metastatic sites were lung and liver. A total of 262 cycles were administrated with median 6 cycles per patient (range: 1–22). All pts were evaluable for toxicity, and 30 pts for response to the treatment. The objective response rate was 26.4% with 2 complete responses respectively. Sixteen (47%) pts had stable disease and 7 (20.5%) had a progression. The tumor control rate was 73.4%. The median TTP was 5.3 months, and the overall survival was 10.1 months. The prognostic factor for longer TTP and survival was the ECOG performance status (PS). The type of regimens was not affected on response rate, TTP and survival. The chemotherapy was generally well tolerated and the most common grade 3–4 toxicities were neutropenia, diarrhea. The non- hematological toxicities were similar for both treatment groups, with more frequent grade =3 neutropenia being noted for the simplified FOLFIRI regimen. Conclusions: The FOLFIRI regimen was demonstrated to have a moderate antitumor activity with acceptable toxicity profiles, and tend to show more favorable outcome for patients with good ECOG PS. No significant financial relationships to disclose.

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

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 9515-9515 ◽  
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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