ITOC2 – 019. An open-label multicenter phase II trial of aviscumine in previously treated patients with unresectable stage IV metastatic melanoma

7707 Background: Systemic chemotherapy with cisplatin/pemetrexed is the approved first line treatment regimen for patients with MM. There is no approved second line therapy. In addition, many patients, especially those >70, cannot tolerate combination chemotherapy. Angiogenesis inhibitors have emerged as attractive potential therapies for MM and SU5416 and PTK787 have previously demonstrated single agent activity. We examined the efficacy of sorafenib, an inhibitor of VEGFR2 and PDGFR-b, in chemotherapy naïve and previously treated patients with MM. Methods: This was an open label single arm phase II study of sorafenib in chemotherapy naïve and previously pemetrexed treated patients with MM. Primary end point was response rate (RR). Secondary objectives were 3-month failure free and overall survival (FFS and OS). Forty-four (44) eligible patients were expected to enroll to differentiate a RR of <5% versus >20%, with a Type I error of 0.0675 and a power of 0.955 Results: Between 10/04 and 8/05, 51 patients were enrolled and treated with sorafenib 400 mg bid. One cycle was defined as 28 days; restaging occurred every 2 cycles. Baseline demographics: M/F (36/15); Median age (69; range 36–88; 45% >70); Histology (epithelial/sarcomatoid/mixed/unknown: 37/4/8/2); pleural/peritoneal MM (46/5); ECOG PS 0/1 (11/40); chemo-naive/prior chemo (20/31). Grade 3/4 toxicities occurring in >10% of patients: Fatigue (12 (25%); 11/1) and hand-foot reaction (6 (13%); 6/0). No study related deaths occurred. Estimates of RR and FFS are based on 47 patients with available follow-up data. Response: CR: 0; PR 2: 4% (95% CI; 1- 14%); SD 28 (60%); PD 11 (23%); unevaluable 6 (14%). Three month FFS was 78%; median FFS was 3.7 months and median OS was 10.7 months. The median FFS were 3.6 and 3.6 months and the median OS were 4.9 and 14.6 months in chemo naïve and previously treated patients, respectively. Conclusions: Sorafenib demonstrated modest activity in this phase II trial but did not meet its primary endpoint. The improved outcome in previously treated patients likely reflects patient selection. Ongoing correlative science studies including expression of p-ERK 1/2, baseline VEGF and PDGF levels, are being performed to help identify patient subsets who may benefit (PR or SD) from sorafenib. No significant financial relationships to disclose.

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A randomized phase II trial of temozolomide (TMZ) and bevacizumab (BEV) or nab-paclitaxel (nab-P)/carboplatin (CBDCA) and bevacizumab (BEV) in patients with unresectable stage IV metastatic melanoma: A North Central Cancer Treatment Group Study (N0775).

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.15_suppl.8532 ◽

2011 ◽

Vol 29 (15_suppl) ◽

pp. 8532-8532 ◽

Cited By ~ 1

Author(s):

L. A. Kottschade ◽

V. Suman ◽

D. G. Perez ◽

R. R. McWilliams ◽

J. S. Kaur ◽

...

Keyword(s):

Treatment Group ◽

Cancer Treatment ◽

Metastatic Melanoma ◽

Phase Ii ◽

Phase Ii Trial ◽

Stage Iv ◽

North Central ◽

Randomized Phase Ii ◽

Unresectable Stage

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Open-label, multicenter, phase II trial of ABI-007 in previously treated and previously untreated patients with metastatic malignant melanoma

Journal of Clinical Oncology ◽

10.1200/jco.2005.23.16_suppl.7558 ◽

2005 ◽

Vol 23 (16_suppl) ◽

pp. 7558-7558 ◽

Cited By ~ 6

Author(s):

E. M. Hersh ◽

S. O’Day ◽

R. Gonzalez ◽

W. E. Samlowski ◽

M. S. Gordon ◽

...

Keyword(s):

Malignant Melanoma ◽

Phase Ii ◽

Phase Ii Trial ◽

Metastatic Malignant Melanoma ◽

Open Label ◽

Multicenter Phase ◽

Previously Treated

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Efficacy and safety of sunitinib in previously treated, advanced non-small cell lung cancer (NSCLC): Preliminary results of a multicenter phase II trial

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.7001 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 7001-7001 ◽

Cited By ~ 37

Author(s):

M. A. Socinski ◽

S. Novello ◽

J. M. Sanchez ◽

J. A. Brahmer ◽

R. Govindan ◽

...

Keyword(s):

Phase Ii ◽

Survival Data ◽

Kinase Inhibitor ◽

Phase Ii Trial ◽

Single Agent ◽

Pulmonary Hemorrhage ◽

Open Label ◽

Initial Report ◽

Multicenter Phase ◽

Previously Treated

7001 Background: Sunitinib malate (SU11248) is an oral, multitargeted tyrosine kinase inhibitor targeting VEGFR, PDGFR, KIT, FLT3 and RET on tumor cells, tumor neovasculature and pericytes. This is the initial report of an open-label, two-stage, multicenter phase II trial evaluating the single-agent activity of sunitinib in refractory NSCLC. Methods: Eligibility criteria included confirmed diagnosis of NSCLC, ECOG PS 0–1, no recent gross hemoptysis, no brain metastases, patients (pts) previously treated with 1–2 chemotherapy regimens, and adequate end-organ function. Pts received sunitinib at 50 mg/day po for 4 weeks (wks) followed by 2 wks off treatment (6 wks considered a cycle). Results: A total of 64 pts were enrolled and 63 pts treated, median age 61 yrs (range 33–87); adenocarcinoma (64%), squamous cell carcinoma (22%), other (14%); 66% male; PS 0:1, 45%:55%; median number of prior regimens: 2 (range 1–4); median time since the prior regimen: 2 months (range 1–21). To date, 63 pts have started cycle 1, 46 cycle 2, 22 cycle 3, 6 cycle 4 and 1 cycle 5. Grade 3–4 toxicities included fatigue/asthenia (21%), nausea (7%), vomiting (7%), abdominal pain (7%), and hypertension (5%). Most toxicities were grade 1–2 and included asthenia/fatigue (68%), anorexia (40%), dyspnea (37%), cough (35%), nausea (33%), mucositis (32%), dysgeusia (25%), diarrhea (21%), vomiting (19%), and constipation (19%). Grade 5 toxicities include pulmonary hemorrhage (n=2) and cerebral hemorrhage (n=1). Thus far, 6 confirmed partial responses have been observed among 63 treated pts (9.5%, 95% CI: 3.6–19.6%). Stable disease has been observed in an additional 12 pts (19.0%). Survival data are pending and will be presented. Conclusions: Sunitinib has provocative single-agent activity in previously treated pts with recurrent and advanced NSCLC, with the level of activity similar to currently approved agents. Sunitinib is well tolerated in this population. The trial is being extended to explore a continuous dosing strategy of sunitinib at 37.5 mg/day po. Based on these results, further trials are warranted and are ongoing with sunitinib in combination with standard agents/regimens. [Table: see text]

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