Dasatinib first-line treatment in gastrointestinal stromal tumors: A multicenter phase II trial of the SAKK (SAKK 56/07).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10033-10033 ◽  
Author(s):  
Michael Montemurro ◽  
Julien Domont ◽  
Aurore Blesius ◽  
Piotr Rutkowski ◽  
Arnaud Roth ◽  
...  
Keyword(s):  
Phase Ii ◽  
Primary Endpoint ◽  
Fdg Pet ◽  
Kinase Inhibitor ◽  
Phase Ii Trial ◽  
Elective Surgery ◽  
Performance Status ◽  
First Line ◽  
Secondary Resistance

10033 Background: First line imatinib has improved the outcome of patients (pts) with gastrointestinal stromal tumor (GIST), but primary and secondary resistance remain a problem. Dasatinib is a second generation tyrosine kinase inhibitor (TKI) and inhibits the activity of bcr-abl, src-family kinases along with a number of other oncogenic kinases including kit. In vitro, dasatinib has shown activity against imatinib-resistant cell lines. Routinely, pts diagnosed with GIST and treated with TKIs are monitored by computed tomography (CT). 18F-fluorodeoxyglucose positron-emission-tomography (FDG-PET) measures tumor metabolic activity for early response assessment, which might be of particular use in the clinical trial setting. Methods: This two-stage phase II trial investigated dasatinib in pts with TKI-naïve GIST. Dasatinib starting dose was 2x70mg/day in pts with histologically proven, FDG-PET positive GIST. Response evaluation was done by serial CT and FDG-PET using EORTC PET response criteria (Young et al. 1999). Elective surgery was allowed after 6 months of trial treatment. Primary endpoint was response (CR+PR) by FDG-PET after one month of dasatinib. Results: 47 of planned 52 pts have been enrolled from December 2007 to November 2011, when the trial was terminated due to slow accrual. 43 pts were eligible. Median age was 61 years, 24 pts were male, 19 female and 41 had a performance status of 0 or 1. At a median follow-up of 11.9 months, 20 pts were still on treatment. Pts went off trial for elective surgery (n=6), progression (n=11), toxicity (n=3), and three patients died (one on-drug). 5% of pts experienced G4, and 38% of pts G3 toxicity, which were most often gastrointestinal or pulmonary. 28% had their dose reduced or interrupted. The primary endpoint, FDG-PET response rate (CR+PR) at 4 weeks was 67% (13 CR, 16 PR, 7 SD, 3 PD, 4 not evaluable). Median progression-free survival is 11.1 months and median overall survival not yet reached. Conclusions: Dasatinib shows promising efficacy in TKI-naïve pts with FDG-PET positive GIST. Mutational data will be presented at the meeting.

Gemcitabine and oxaliplatin (GEMOX) alone or in combination with cetuximab as first-line treatment for advanced biliary cancer: Final analysis of a randomized phase II trial (BINGO).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4032-4032 ◽  
Author(s):  
David Malka ◽  
Laetitia Fartoux ◽  
Vanessa Rousseau ◽  
Tanja Trarbach ◽  
Eveline Boucher ◽  
...  
Keyword(s):  
Phase Ii ◽  
Primary Endpoint ◽  
Mutational Analysis ◽  
Metabolic Response ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Objective Response ◽  
First Line ◽  
Open Label ◽  
Randomized Phase Ii

4032 Background: Gemcitabine-platinum chemotherapy (CTx) regimens are widely accepted as first-line standard of care for patients (pts) with advanced biliary cancers (ABC). EGFR overexpression has been observed in ABC, suggesting that the combination with anti-EGFR monoclonal antibodies may be appropriate. Methods: Patients with ABC, WHO performance status (PS) 0-1, and without prior palliative CTx were eligible for this international, open-label, two-stage, non-comparative, randomized phase II trial. Patients received GEMOX (gemcitabine, 1 g/m² [10 mg/m²/min] at day [D]1 + oxaliplatin, 100 mg/m² at D2, arm A) or GEMOX + cetuximab (500 mg/m² at D1 or 2, arm B), every 2 weeks. The primary endpoint was crude 4-month progression-free survival (PFS) rate (H0, <40%; H1, ≥60%; planned sample size, 100 pts, increased to 150 pts by amendment to allow subgroup analyses). Secondary endpoints were objective response rate (ORR), disease control rate (DCR), PFS, overall survival (OS), and toxicity (NCI-CTC v3.0). Exploratory endpoints included early metabolic response as assessed by PET at 1 month, and tumor KRAS mutational analysis. Results: From Oct. 2007 to Dec. 2009, we enrolled 150 pts (median age, 62 years; male, 57%; metastatic, 79%; cholangiocarcinoma, 84%; median follow-up, 30 months) (Table). Conclusions: GEMOX-cetuximab regimen was well tolerated and met its primary endpoint (4-month PFS ≥60%). However, median PFS and OS were similar in both arms. Exploratory analyses (e.g., KRAS tumor status) are underway to identify pt subgroups deriving benefit from the addition of cetuximab to CTx. [Table: see text]

Bevacizumab (B) plus erlotinib (E) for patients (pts) with recurrent ovarian (OC) and fallopian tube (FT) cancer: Preliminary results of a multi-center phase II trial

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5018-5018 ◽  
Author(s):  
G. Friberg ◽  
A. M. Oza ◽  
R. J. Morgan ◽  
E. E. Vokes ◽  
D. R. Gandara ◽  
...  
Keyword(s):  
Growth Factor ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Trial ◽  
Bowel Perforation ◽  
Performance Status ◽  
Growth Factor Receptor ◽  
Ca 125 ◽  
Efficacy Evaluation ◽  
Ecog Performance Status

5018 Background: The epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) are commonly over-expressed in OC and correlate with poor prognosis. The anti-VEGF antibody B and the EGFR tyrosine kinase inhibitor E have each demonstrated activity in OC. Dual inhibition with BE may overcome mechanisms of resistance encountered with either agent alone. Methods: We are conducting a 2-stage phase II trial of BE in pts with recurrent OC, primary peritoneal, and FT cancer. Eligible pts had ≤ 2 prior chemo regimens for recurrent or refractory disease; no prior VEGF or EGFR inhibitors; ECOG performance status (PS) 0–2; measurable disease; normal organ function; no proteinuria (<1000 mg/24 hours). B 15 mg/kg was given IV on day 1 every 21 days and daily E 150 mg PO was given continuously. CT scans were obtained every 9 weeks. 2 responses are required in the first stage to justify accrual into a second stage. Results: 13 pts enrolled at 3 centers from 7/05 to 10/05. Median age: 56 (range 45–70). PS (N with 0/1/2): 6/4/3. Primary site (N): OC 11, FT 2. Primary platinum response (N): refractory 4, resistant (<12 mo PFS) 2, sensitive (≥12 mo) 7. Total prior chemo regimens (N with 1/2/3): 1/8/4. 55 cycles of BE have been delivered (median 4, range 1–8). 12 pts are evaluable for response (1 too early). There has been 1 major response (8%). 8 patients (67%) had stable disease (SD). 1 pt with SD met 75% CA-125 response criteria. 8 pts remain on study. Median PFS has not been reached (median f/u 2.2 months). Attributable toxicities (N with grade 1/2/3/4): rash 4/7/0/0, diarrhea 6/1/2/0, stomatitis 3/1/0/0, myalgias 4/0/0/0, proteinuria 3/0/0/0, bilirubin 0/2/0/0. There were 2 bowel perforations (grade 3/4): both had 2 prior regimens, peritoneal implants >1 cm, 3 doses of B (last was 10 and 42 days prior), and small bowel obstructions in the preceding 28 days. Conclusions: The first stage of accrual is complete and further enrollment is on hold pending continued efficacy evaluation. There appeared to be an increased rate of bowel perforation, and identification of potential risk factors for this event would be critical for further development of this combination. Updated results will be presented. Supported by NCI Grant N01-CM-17102. [Table: see text]

A phase II trial of BAY 43–9006 in patients with recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC): A Southwest Oncology Group (SWOG) trial

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5550-5550 ◽  
Author(s):  
S. K. Williamson ◽  
J. Moon ◽  
C. H. Huang ◽  
P. Guaglianone ◽  
G. T. Wolf ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Phase Ii ◽  
Squamous Cell ◽  
Survival Data ◽  
Tyrosine Kinases ◽  
Kinase Inhibitor ◽  
Phase Ii Trial ◽  
Performance Status

5550 Background: Bay 43–9006 (Sorafenib) is a potent Raf-1 and B-Raf kinase inhibitor of the RAS/RAF/MEK/ERK pathway. The compound also inhibits protein tyrosine kinases associated with VEGFR-2 and 3 as well as PDGFR-B. We conducted a phase II trial to evaluate the efficacy of BAY 43–9006 in chemotherapy naive patients with metastatic or recurrent HNSCC. Methods: Chemotherapy naïve patients with histologically proven squamous cell carcinoma of the head and neck either metastatic, persisted or recurred following definitive surgery and/or radiation therapy, and not amenable to salvage surgical resection were eligible. Patients may have received only one induction or adjuvant chemotherapy regimen provided that at least 6 months have elapsed since the last course was administered. Patients must have adequate cardiac, hematologic, renal and hepatic function and a Zubrod Performance Status of ≤ 1. Specimens were obtained from either archival or fresh pre-treatment biopsies and at the time of progression of disease for molecular correlative studies. BAY 43–9006 was administered orally at 400 mg BID on a continuous basis, in 28-day cycles. Responses were evaluated every 8 weeks according to RECIST criteria. Initially 20 patients will be registered. If one or more confirmed responses are observed in the first 20 patients, an additional 20 patients will be registered. Results: Thirty-eight patients (31 males, 7 females, median age 64 years) have been enrolled to date. Twenty-seven patients are evaluable for toxicity. The drug was generally well tolerated. There have been 2 Grade 4 toxic events - one cerebral ischemia and an asymptomatic pulmonary embolus. Grade 3 toxicities include 2 patients with hand/foot syndrome, 4 with stomatitis or oral pain, and one episode each of anorexia, dysphagia, hypertension, and ulceration. The most common grade 2 toxic events were fatigue (8 pts.), anorexia (8 pts.), stomatitis (5 pts.), and hypertension (4 pts.). Complete accrual to 40 patients is anticipated by January 31, 2006. Conclusions: BAY 43–9006 is well tolerated. Updated toxicity data will be reported. Preliminary response, time to progression and survival data will be presented. [Table: see text]

Randomized phase II trial of the multi-kinase inhibitor sorafenib versus interferon (IFN) in treatment-naïve patients with metastatic renal cell carcinoma (mRCC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4501-4501 ◽  
Author(s):  
B. Escudier ◽  
C. Szczylik ◽  
T. Demkow ◽  
M. Staehler ◽  
F. Rolland ◽  
...  
Keyword(s):  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Trial ◽  
Prognostic Score ◽  
Primary Objective ◽  
Phase Iii ◽  
First Line ◽  
First Line Therapy ◽  
Randomized Phase Ii ◽  
Grade 3

4501 Background: Sorafenib, an oral multi-kinase inhibitor that targets tumor growth and vascularization, significantly prolonged PFS in a Phase III trial with previously treated mRCC patients. This randomized Phase II trial investigated the efficacy and tolerability of sorafenib compared with IFN in first-line therapy of patients with clear-cell RCC. Methods: Untreated patients with mRCC were stratified by MSKCC prognostic score and randomized to receive continuous oral sorafenib 400 mg bid or IFN 9 million units tiw, with an option of dose escalation (600 mg bid sorafenib) or crossover from IFN to sorafenib upon disease progression. The study assessed PFS at 99 events as primary objective, best response (RECIST), overall survival, health-related quality of life, and adverse events (AEs). Results: Baseline characteristics of 188 patients (sorafenib n=97; IFN n = 91) were: median age 62.0 years; MSKCC score: 57% low, 41% intermediate, 1% high; prior nephrectomy: 82%; ECOG 0:1, 55.3%:44.7%. As of January 6, 2006, PFS events have been reported for 64 (34%) patients. Preliminary data showed drug-related AEs of any severity (sorafenib vs IFN) in 50.5% vs 51.6% of patients (≥grade 3: 8.2% vs 11.0%), including diarrhea (24.7% vs 5.5%), fatigue (14.4% vs 20.9%), fever (2.1% vs 18.7%), hypertension (13.4% vs 0%), nausea (5.2% vs 13.2%), flu-like syndrome (1.0% vs 6.6%), hand-foot skin reaction (6.2% vs 0%), and rash/desquamation (4.1% vs 0%). Drug-related metabolic/laboratory abnormalities at grade 3 (no grade 4) comprised hypophosphatemia (21.7% vs. 0%), lipase elevation (5.6% vs. 11.1%), anemia (0% vs. 5.3%) and hypoalbuminemia (0% vs. 3.6%). Five patients receiving IFN withdrew from treatment due to AEs, whereas only one patient withdrew from sorafenib. Conclusions: Sorafenib was generally well tolerated in RCC patients in the first-line setting, with relatively infrequent drug-related AEs ≥grade 3. Full PFS data will be presented at the meeting. [Table: see text]

First-line phase II trial of sorafenib (BAY 43–9006) in patients with advanced renal cell carcinoma unsuitable for cytokine treatment

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15640-15640 ◽  
Author(s):  
P. Maroto-Rey ◽  
J. Bellmunt ◽  
J. M. Trigo ◽  
V. Guillem ◽  
J. A. López-Martín ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Renal Cell ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Antiangiogenic Agents ◽  
First Line ◽  
Ecog Performance Status ◽  
Cytokine Treatment

15640 Background: Sorafenib (BAY 43–9006) is a serine/threonine and receptor tyrosine kinase inhibitor that prevents tumor cell proliferation and angiogenesis. The objective of this open-label, phase II trial was to determine median progression-free survival (PFS) following sorafenib therapy in patients with renal cell carcinoma (RCC) unsuitable for cytokine treatment. Methods: Eligible patients had cytologically or histologically confirmed clear cell RCC; Eastern Cooperative Oncology Group (ECOG) Performance Status 0–1; adequate renal, liver and medullar function; no active central nervous system metastases; had received no previous treatment with antiangiogenic agents; and had at least one evaluable lesion. Sorafenib was given as first-line treatment in patients unsuitable for cytokine therapy, defined as being intolerant to or ineligible for immunotherapy. Treatment consisted of oral sorafenib 400mg twice daily continuously until disease progression or unacceptable toxicity. The primary endpoint was PFS; secondary endpoints were response rate according to Response Evaluation Criteria in Solid Tumors, tolerability and overall survival. Results: Twenty-six patients were enrolled between March and July 2006 (median age: 68.5 years [48–82]; male/female: 17/9, ECOG Performance Status 0: 11 patients; prior nephrectomy: 19 patients). The main metastatic locations were lung and bone, 14 patients had = 2 metastatic lesions, and 2 patients had abnormal lactate dehydrogenase levels. As of 31 December 2006, with a median follow-up of 6.4 months, the median PFS had not been reached. In 19 patients evaluable for response, the overall clinical benefit rate was 68.4% (1 complete response; 1 partial response; 11 stable disease). Six patients experienced serious adverse events, only one of which was related to treatment. Conclusions: Sorafenib first-line therapy is a tolerable alternative for patients unsuitable for cytokine treatment. Final PFS data will be available in June 2007. No significant financial relationships to disclose.

ASPIRATION: Phase II study of continued erlotinib beyond RECIST progression in Asian patients (pts) with epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS7614-TPS7614 ◽  
Author(s):  
Keunchil Park ◽  
Chun-Ming Tsai ◽  
Myung-ju Ahn ◽  
Chong-Jen Yu ◽  
Sang-We Kim ◽  
...  
Keyword(s):  
Phase Ii ◽  
Primary Endpoint ◽  
Egfr Mutation ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Phase Iii ◽  
Egfr Mutations ◽  
First Line ◽  
Life Threatening ◽  
Pre Treatment

TPS7614 Background: First-line erlotinib (an EGFR tyrosine-kinase inhibitor) significantly increased progression-free survival (PFS) vs chemotherapy in phase III trials of pts with EGFR mutation-positive NSCLC. Discontinuation of erlotinib on RECIST disease progression (PD) may lead to rapid disease flare-up; continued erlotinib beyond RECIST PD may extend clinical benefit by slowing progression of this life-threatening disease. We describe ASPIRATION, a large, Asian, multicenter, single-arm, open-label, phase II trial (NCT01310036), which will increase understanding of first-line erlotinib and erlotinib continuation beyond RECIST PD in pts with EGFR-mutated NSCLC. Methods: Pts (n=204) ≥18 yrs with stage IV/recurrent NSCLC, ≥1 measurable lesion (≥10mm), ECOG performance status (PS) 0-2 and positive EGFR mutation status established by local pathology laboratory (that underwent voluntarily QA/QC) are eligible. All pts receive erlotinib 150mg/day. Tumor response is evaluated using RECIST (v1.1). The primary endpoint is PFS. At investigator's discretion, pts may continue on erlotinib beyond RECIST PD, e.g. if they have slow PD (>6 months of partial response/stable disease), asymptomatic minimal PD, or new brain metastasis controlled locally. Pts should not continue erlotinib if they have extracranial PD with symptoms; rapid PD and/or worsening of PS; or life-threatening complications. Pts continuing erlotinib who present with second RECIST PD will discontinue. Secondary endpoints include objective response rate, disease control rate, overall survival, and safety. For the exploratory biomarker study, pre-treatment tumor tissue blocks are collected; remaining tissue (after EGFR mutation testing for eligibility) will be analyzed centrally to study the association of biomarkers and clinical outcomes. Pre-treatment and post-treatment plasma and serum samples will be obtained at various time points for biomarker assays, including EGFR mutations and other candidate NSCLC biomarkers. Recruitment began in Apr 2011; the estimated final data collection for the primary endpoint is Dec 2014.

Preoperative chemoradiotherapy in non-small cell lung cancer (NSCLC) patients with operable stage IIIB disease. A phase II trial of the Swiss Group for Clinical Cancer Research (SAKK)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18021-18021 ◽  
Author(s):  
M. Pless ◽  
R. Stupp ◽  
R. Kann ◽  
A. Zouhair ◽  
M. Mayer ◽  
...  
Keyword(s):  
Phase Ii ◽  
Primary Endpoint ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Objective Response ◽  
Locally Advanced ◽  
Stage Iiib ◽  
R0 Resection ◽  
Clinical Cancer Research ◽  
Concomitant Boost

18021 Background and Methods: Outcome of patients (pts) with locally advanced NSCLC treated with radio- or chemoradiotherapy is poor. This two-stage phase II trial (planned sample size 46) aimed at evaluating feasibility and outcome of a tri-modality concept of neoadjuvant chemotherapy (CT), radiotherapy (RT) followed by definitive surgery in operable, stage IIIB NSCLC pts. Treatment consisted of 3 cycles of cisplatin (100 mg/m2) and docetaxel (85 mg/m2) followed by accelerated, concomitant boost RT (44 Gy/22 fx) and surgery. Primary endpoint is event-free survival at 1 year. Operable pts up to age 75 and a performance status of 0–1 with stage IIIB NSCLC (pleural effusion excluded) were eligible. Results: Forty-five eligible pts (46 accrued) with a median age was 60 years (range 28–70) were treated between September 2001 and May 2006. Tumor location was right-sided in 28 pts and left-sided in 17 pts. Histology was squamous cell 42%, large cell 11%, adeno-13% and undifferentiated carcinoma 33%. N3-disease was present in 29%, T4 stage in 78%. CT (45 pts) and RT (34 pts) were delivered as prescribed in >80% of cycles. The median time from enrollment to surgery was 3.7 months (2.8 - 5.2). The objective response rate after CT was 53% (95% c.i. 38–68%), after additional RT 67% (51–80%). Surgery (pneumonectomy in 17) was performed in 31 pts (69%), with an R0 resection in 24 pts. Median duration of hospitalization was 12 days (8–134). Two pts died in the perioperative phase due to ARDS and a cerebro-vascular event, respectively. Mature results of the primary endpoint and overall survival will be available at the ASCO meeting. Conclusions: Combined multimodality treatment strategy is feasible in a subgroup of patients, with acceptable toxicity. About two thirds of patients responded to the induction therapy, and were able to undergo subsequent surgery. No significant financial relationships to disclose.

Phase II trial of irinotecan, S-1, and bevacizumab (IRIS/Bev) combination chemotherapy as second line for advanced colorectal cancer (NCCSG04).

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 496-496
Author(s):  
Yasumasa Takii ◽  
Kouichi Hurukawa ◽  
Satoshi Maruyama ◽  
Toshiyuki Yamazaki ◽  
Jun Nishimura ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Phase Ii Trial ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Free Survival ◽  
Line Therapy

496 Background: The FIRIS study (Muro K et al. Lancet Oncol 2010;11:853-860) previously demonstrated the non-inferiority of Irinotecan plus S-1 (IRIS) to FOLFIRI for metastatic colorectal cancer (mCRC), with progression-free survival as the primary endpoint. IRIS plus bevacizumab (IRIS/Bev) was reported an active and generally well-tolerated first-line treatment for mCRC (Yuki et al. ASCO 2012 #3593). We planned a Phase II trial to evaluate the efficacy and safety of IRIS/Bev as second-line therapy for patients with mCRC. Methods: The study design was multicenter, single-arm, open-label phase II study. Eligible patients had to have mCRC with confirmed diagnosis of adenocarcinoma, history of oxaliplatin containing regimen as first-line therapy, an age from 20 to 80 years, ECOG performance status (PS) of 0-1. S-1 65 mg/m2 daily p.o. was given on days 1-14 and Irinotecan 75mg/m2 and Bevacizumab 10mg/kg i.v. were given on days 1 and 15 of a 28-day cycle. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall response rate (OR), overall survival (OS), time to treatment failure (TTF) and safety. Results: From 08/12 until 11/06, 35 patients were enrolled. One patient did not start therapy. Thirty-four patients were investigated. Median age was 63 years (range, 38 to 82). Twenty-five patients were male. The mean of relative dose intensity of TS-1/Irinotecan/Bev were respectively 92.1%/87.0%/86.2%. The OR was 21.1% (7/33) and disease control rate was 84.8% (28/33). Median PFS was 9.3 months, median TTF was 8.2 month and median survival time 23.1 month. On safety analysis, the incidence of grade 3 or 4 adverse reactions were as follows: neutropenia, 14.7%; fatigue, 14.7%; white blood cell decreased, 11.8%; anorexia, 8.8%; anemia, 8.8%; diarrhea, 2.9%; proteinuria, 5.9%; thromboembolic event, 2.9%. Conclusions: IRIS/Bev is an active and well-tollarated second-line treatment for patients with mCRC. Clinical trial information: UMIN000001631.

A phase II trial of regorafenib (REGO) in patients (pts) with advanced Ewing sarcoma and related tumors (EWS) of soft tissue and bone: SARC024 trial results.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11005-11005 ◽  
Author(s):  
Steven Attia ◽  
Vanessa Bolejack ◽  
Kristen N. Ganjoo ◽  
Suzanne George ◽  
Mark Agulnik ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Phase Ii Trial ◽  
Common Grade ◽  
Duration Of Response ◽  
The Difference ◽  
Line Of Therapy

11005 Background: Pazopanib is approved for soft tissue sarcoma pts after failure of other therapy, but there are few subtype-specific data regarding kinase inhibitor activity. We report on a single arm, phase II trial of REGO in advanced EWS. Methods: EWS pts (age > 18, ECOG 0-2, good organ function) who had at least 1 line of therapy and had PD within 6 mo were eligible. Prior oral kinase inhibitors were not allowed. Initial REGO dose was 160 mg PO QD x21 q28d. Dose reductions were employed for toxicity and AEs. The primary endpoint was PFS at 8 weeks (PFS8w) employing RECIST 1.1. Sample size of 30 allowed determination of the difference between PFS8w of 50% vs 25% with alpha = 0.05 and power of 91%. Results: 30 pts (median age 32, range 19-65; M/F = 20/10; ECOG 0/1/2 = 16/13/1; bone, 12; soft tissue, 18; median prior treatments 5, range 1-10) enrolled at 14 US sites (09/2014-03/2016). Most common grade (G3) toxicities were hypophosphatemia (6), hypertension (2), high ALT (2) and 1 each: fatigue, abd pain, diarrhea, hypokalemia, oral mucositis, neutropenia and rash; no G4 toxicities were noted. 13 pts required ≥1 dose reduction, most commonly hypophosphatemia (n = 7); 2 stopped REGO for toxicity. There was 1 death in the 30 day post study period, not REGO related. Median dose at study end: 140 mg (3.5 tabs, range 80-160 mg) 3 wks on/1wk off. 18/30 pts were without PD at 8 wks. Median PFS: 3.6 mo (95%CI 2.8-3.8 mo). PFS8w by KM was 73% (95%CI 57-89%). Best responses: PR/SD/PD/not evaluable of 3/18/7/2, for RECIST RR 10%. Two pts with PR had EWSR1 translocation by FISH; a third had CIC-DUX4. Median duration of response: 5.5 mo (95%CI 2.9-8.0). Median OS is not reached. Conclusions: The substudy met its primary endpoint. REGO toxicity was similar to that seen previously. Enrollment continues in LPS and OGS cohorts, and is being expanded to further study variant EWS without EWSR1-FLI1 fusion. Study of the existing tissue may elucidate which EWS patients may benefit from REGO. Clinical trial information: NCT02048371.

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