Dovitinib as second-line therapy in patients with fibroblast growth factor receptor 2 (FGFR2)-mutated or non-mutated advanced and/or metastatic endometrial cancer (EC): A single-arm, multicenter, phase II study.

TPS5616 Background: Despite the use of combination chemotherapy and introduction of novel targeted agents, the prognosis for advanced and/or metastatic EC is challenging. The occurrence of somatic activating FGFR2 mutations in EC suggests an opportunity for testing FGFR inhibitors. Dovitnib (DOV) is a potent receptor tyrosine kinase inhibitor of vascular endothelial growth factor receptor, platelet-derived growth factor receptor and FGFR. The objective of the study is to investigate the efficacy and safety of DOV as second-line therapy in patients (pts) with advanced and/or metastatic EC. Methods: This multicenter, non-randomized, open label, single-arm, phase II study (NCT01379534) will enroll adult female pts (N~80) with either FGFR2 mutated (group 1) or non-mutated (group 2) histologically confirmed advanced and/or metastatic EC, who have documented radiological evidence of progressive disease (RECISTv1.1) after 1 prior line of chemotherapy, excluding adjuvant therapy. Eligible pts also need to have ≥1 measurable lesion (RECISTv1.1) and ECOG performance status ≤ 2. Pts will receive oral DOV of 500 mg/day, on a 5-days-on / 2-days-off dosing schedule until disease progression, unacceptable toxicity, death, or discontinuation due to any other reason. Primary endpoint is 18-week progression-free survival (PFS) rate (local review; RECIST v1.1) and secondary endpoints include overall response rate, disease control rate, duration of response, PFS, overall survival, safety, tolerability, pharmacokinetics, and pharmacodynamic effect of DOV on soluble plasma biomarker expression level. A 2-stage design with Bayesian interim monitoring (interim for futility analyses) will be used in each group. For stage 1, 20 pts will be enrolled into each group. If ≥ 8 of the first 20 pts with measurable disease at baseline in either group are progression-free after 18 weeks of treatment, 20 additional pts will be enrolled into that group in stage 2. Preliminary results for each group will be evaluated in the interim analysis. As of 20 January 2013, 43 pts have been enrolled (12 with and 31 without FGFR2 mutations). Clinical trial information: NCT01379534.

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An open-label multicenter phase II study of oral lapatinib (GW572016) as single agent, second-line therapy in patients with metastatic colorectal cancer

Journal of Clinical Oncology ◽

10.1200/jco.2005.23.16_suppl.3583 ◽

2005 ◽

Vol 23 (16_suppl) ◽

pp. 3583-3583 ◽

Cited By ~ 22

Author(s):

A. L. A. Fields ◽

D. A. Rinaldi ◽

C. A. Henderson ◽

C. J. Germond ◽

L. Chu ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Phase Ii ◽

Phase Ii Study ◽

Single Agent ◽

Second Line ◽

Open Label ◽

Second Line Therapy ◽

Multicenter Phase ◽

Line Therapy

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A phase II study of second-line S-1/CPT-11+bev for advanced colon cancer (NCCSG04): Subset analysis by K-ras, EGFR, UGT1A1, and previous bevacizumab.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.564 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 564-564

Author(s):

Yasumasa Takii ◽

Kouichi Furukawa ◽

Satoshi Maruyama ◽

Toshiyuki Yamazaki ◽

Atsushi Nishimura ◽

...

Keyword(s):

Phase Ii ◽

Phase Ii Study ◽

Performance Status ◽

Line Treatment ◽

Second Line ◽

Open Label ◽

Ecog Performance Status ◽

Line Therapy ◽

Negative Case ◽

Wild Group

564 Background: We planned a phase II trial to evaluate the efficacy and safety of irinotecan, S-1, and bevacizumab (IRIS/Bev) as second-line therapy for patients with metastatic colorectal cancer (mCRC). The result of this study was reported an active and generally well-tolerated 2nd-line treatment for mCRC (Takii et al. ASCO-GI 2013 #496). We analyzed subset of EGFR, K-ras, UGT1A1, and previous Bev. 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/m2and bevacizumab 10mg/kg i.v. were given on days 1 and 15 of a 28-day cycle. We retrospectively examined progression-free survival (PFS), overall response rate (OR), overall survival (OS), time to treatment failure (TTF) and safety by K-ras, EGFR, UGT1A1, and previous Bev status. Results: Thirty-four patients were investigated. The OR was 21.1% (7/33) and disease control rate was 84.8% (28/33). Median PFS was 8.9 months, median TTF was 8.2 months and median OS was 23.4 months. Median PFS was 9.9 months on K-ras wild group and 6.6 months on K-ras mutant group (p = 0.517). Median OS was not reached on K-ras wild group and 16.4 months on K-ras mutant group (p = 0.097). The EGFR-negative case was three cases, and it did not become a data to compare because of small number. Median PFS was 8.5 months on previous Bev group and 9.9 months on previous no-Bev group (p = 0.637). Median OS was not reached on previous Bev group and 23.1 months on previous no-Bev group (p = 0.701). Median PFS, TTF and OS was no different between UGT1A1 wild group and mutant group. On safety analysis, there were no different between the two groups, respectively. Conclusions: IRIS/Bev is an active and well-tolerated second-line treatment for patients with mCRC. Only K-ras status influendced OS. Clinical trial information: UMIN000001631.

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An open-label, single-arm Phase II study of intravenous weekly (Days 1 and 8) topotecan in combination with carboplatin (Day 1) every 21days as second-line therapy in patients with platinum-sensitive relapsed ovarian cancer

Gynecologic Oncology ◽

10.1016/j.ygyno.2010.10.011 ◽

2011 ◽

Vol 120 (1) ◽

pp. 38-42 ◽

Cited By ~ 5

Author(s):

Peter G. Rose ◽

Bradley J. Monk ◽

Diane Provencher ◽

Jean Hartney ◽

Philippe Legenne ◽

...

Keyword(s):

Ovarian Cancer ◽

Phase Ii ◽

Phase Ii Study ◽

Second Line ◽

Open Label ◽

Second Line Therapy ◽

Platinum Sensitive ◽

Line Therapy

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An open-label, single arm, phase II study of IV weekly (days 1 and 8) topotecan in combination with carboplatin (day 1) every 21 days as second-line therapy in subjects with platinum-sensitive relapsed ovarian cancer: First stage results

Journal of Clinical Oncology ◽

10.1200/jco.2008.26.15_suppl.16518 ◽

2008 ◽

Vol 26 (15_suppl) ◽

pp. 16518-16518 ◽

Cited By ~ 2

Author(s):

P. E. Schwartz ◽

P. G. Rose ◽

B. J. Monk ◽

D. Provencher ◽

B. Dharan ◽

...

Keyword(s):

Ovarian Cancer ◽

Phase Ii ◽

Phase Ii Study ◽

Second Line ◽

Open Label ◽

Second Line Therapy ◽

Platinum Sensitive ◽

Line Therapy

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Faculty of 1000 evaluation for Randomized phase II study of lonaprisan as second-line therapy for progesterone receptor-positive breast cancer.

F1000 - Post-publication peer review of the biomedical literature ◽

10.3410/f.718021759.793480257 ◽

2013 ◽

Author(s):

Ana Maria Gonzalez-Angulo

Keyword(s):

Breast Cancer ◽

Progesterone Receptor ◽

Phase Ii ◽

Phase Ii Study ◽

Second Line ◽

Second Line Therapy ◽

Line Therapy ◽

Randomized Phase Ii ◽

Positive Breast Cancer

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NFB-08. PHASE II STUDY OF AXITINIB IN PATIENTS WITH NEUROFIBROMATOSIS TYPE 2 AND PROGRESSIVE VESTIBULAR SCHWANNOMAS

Neuro-Oncology ◽

10.1093/neuonc/noaa222.612 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii419-iii419

Author(s):

Sheetal Phadnis ◽

Mari Hagiwara ◽

Anna Yaffe ◽

Carole Mitchell ◽

Theodore Nicolaides ◽

...

Keyword(s):

Growth Factor ◽

Phase Ii ◽

Kinase Inhibitor ◽

Phase Ii Study ◽

Growth Factor Receptor ◽

Neurofibromatosis Type ◽

Neurofibromatosis Type 2 ◽

Vestibular Schwannomas ◽

Volumetric Response

Abstract INTRODUCTION Vascular endothelial growth factor receptor (VEGFR), platelet derived growth factor receptor (PDGFR), and c-KIT represent clinically and/or preclinically validated molecular targets in vestibular schwannomas. We conducted a single institution, prospective, open-label, two-stage phase II study (ClinicalTrials.gov identifier NCT02129647) to estimate the response rate to axitinib, an oral multi-receptor tyrosine kinase inhibitor targeting VEGFR, PDGFR and c-KIT, in neurofibromatosis type 2 (NF2) patients with progressive vestibular schwannomas (VS). METHODS NF2 patients older than 5 years with at least one volumetrically measurable, progressive VS were eligible. The primary endpoint was to estimate the objective volumetric response rates to axitinib. Axitinib was given continuously in 28-day cycles for up to of 12 cycles. Response was assessed every 3 months with MRI using 3-D volumetric tumor analysis and audiograms. Volumetric response and progression were defined as ≥20% decrease or increase in VS volume, respectively. RESULTS Twelve eligible patients (ages: 14–56 years) were enrolled on this study. Seven of twelve patients completed 12 cycles (range: 2 to 12 cycles). We observed two imaging and three hearing responses. Best volumetric response was -53.9% after nine months on axitinib. All patients experienced drug-related toxicities, the most common adverse events were diarrhea, hematuria and skin toxicity, not exceeding grade 2 and hypertension, not exceeding grade 3. CONCLUSIONS While axitinib has modest anti-tumor activity in NF2 patients, it is more toxic and appears to be less effective compared to bevacizumab. Based on these findings, further clinical development of axitinib for this indication does not appear warranted.

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