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

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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Sorafenib in malignant mesothelioma (MM): A phase II trial of the Cancer and Leukemia Group B (CALGB 30307)

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.7707 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 7707-7707 ◽

Cited By ~ 11

Author(s):

P. A. Janne ◽

X. F. Wang ◽

L. M. Krug ◽

L. Hodgson ◽

E. E. Vokes ◽

...

Keyword(s):

Phase Ii ◽

Science Studies ◽

Phase Ii Trial ◽

Single Agent ◽

Angiogenesis Inhibitors ◽

Attractive Potential ◽

Type I ◽

Open Label ◽

Previously Treated Patients ◽

Previously Treated

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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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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Multicenter Phase II Trial of Temozolomide in Patients With Anaplastic Astrocytoma or Anaplastic Oligoastrocytoma at First Relapse

Journal of Clinical Oncology ◽

10.1200/jco.1999.17.9.2762 ◽

1999 ◽

Vol 17 (9) ◽

pp. 2762-2762 ◽

Cited By ~ 529

Author(s):

W.K. Alfred Yung ◽

Michael D. Prados ◽

Ricardo Yaya-Tur ◽

Steven S. Rosenfeld ◽

Michael Brada ◽

...

Keyword(s):

Phase Ii ◽

Safety Profile ◽

Anaplastic Astrocytoma ◽

Phase Ii Trial ◽

Single Agent ◽

Objective Response ◽

Survival Rates ◽

Open Label ◽

Multicenter Phase ◽

First Relapse

PURPOSE: To determine the antitumor efficacy and safety profile of temozolomide in patients with malignant astrocytoma at first relapse. PATIENTS AND METHODS: This open-label, multicenter, phase II trial enrolled 162 patients (intent-to-treat [ITT] population). After central histologic review, 111 patients were confirmed to have had an anaplastic astrocytoma (AA) or anaplastic mixed oligoastrocytoma. Chemotherapy-naive patients were treated with temozolomide 200 mg/m2/d. Patients previously treated with chemotherapy received temozolomide 150 mg/m2/d; the dose could be increased to 200 mg/m2/d in the absence of grade 3/4 toxicity. Therapy was administered orally on the first 5 days of a 28-day cycle. RESULTS: Progression-free survival (PFS) at 6 months, the primary protocol end point, was 46% (95% confidence interval, 38% to 54%). The median PFS was 5.4 months, and PFS at 12 months was 24%. The median overall survival was 13.6 months, and the 6- and 12-month survival rates were 75% and 56%, respectively. The objective response rate determined by independent central review of gadolinium-enhanced magnetic resonance imaging scans of the ITT population was 35% (8% complete response [CR], 27% partial response [PR]), with an additional 26% of patients with stable disease (SD). The median PFS for patients with SD was 4.4 months, with 33% progression-free at 6 months. Maintenance of progression-free status and objectively assessed response (CR/PR/SD) were both associated with health-related quality-of-life (HQL) benefits. Adverse events were mild to moderate, with hematologic side effects occurring in less than 10% of patients. CONCLUSION: Temozolomide demonstrated good single-agent activity, an acceptable safety profile, and documented HQL benefits in patients with recurrent AA.

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

European Journal of Cancer ◽

10.1016/j.ejca.2015.01.032 ◽

2015 ◽

Vol 51 ◽

pp. S7

Author(s):

Trefzer Uwe ◽

Gutzmer Ralf ◽

Wilhelm Tabea ◽

Schenck Florian ◽

Kähler Katharina C. ◽

...

Keyword(s):

Metastatic Melanoma ◽

Phase Ii ◽

Phase Ii Trial ◽

Stage Iv ◽

Open Label ◽

Multicenter Phase ◽

Unresectable Stage ◽

Previously Treated Patients ◽

Previously Treated

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Phase II trial of veliparib (V) in patients (pts) with previously treated BRCA or PALB2-mutated (mut) pancreas adenocarcinoma (PC).

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.358 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 358-358 ◽

Cited By ~ 1

Author(s):

Maeve Aine Lowery ◽

David Paul Kelsen ◽

Sloane C. Smith ◽

Malcolm Moore ◽

Hedy Lee Kindler ◽

...

Keyword(s):

Phase Ii ◽

Phase Ii Trial ◽

Treatment Plan ◽

Single Agent ◽

Error Rates ◽

Stage Iii ◽

Type I ◽

Open Label ◽

Increased Risk ◽

Previously Treated

358 Background: BRCA1, BRCA2, and PALB2 germline mutations are associated with an increased risk of PC. Other BRCA-associated cancers have demonstrated increased sensitivity to PARP inhibitors (PARPi) and early trials have shown activity of PARPi in untreated BRCAmut PC. We evaluated theactivity of V in patients with previously treated BRCA/PALB2mutPC. Methods: Eligibility: BRCA1/2, or PALB2mutPC, at least 1 and up to 2 prior treatment regimens, measurable stage III/IVPC; ECOG 0-1. Treatment Plan: V 300mg BID (N= 3 pts), then V 400mg BID day1- 28. Primary endpoint: RECIST 1.1 response rate (RR). Statistical plan: Single-arm, non-randomized, open-label, phase II, two-stage design, unacceptable RR 10%, promising 28%, type I, II error rates 10%. Secondary endpoints: progression-free survival (PFS), duration of response, overall survival, safety, tolerability and archival tumor analyses. Results: Between 05/12 and 12/13, N= 16 enrolled. Male= 8, Female= 8. Median age= 52 years (range 43- 77). BRCA1 mut=5. BRCA2 mut=11. N= 1AJCC stage III PC, N= 15 AJCC stage IV PC. N= 8 and N= 8 (50%) had 1 and 2 prior lines of therapy respectively. N= 13 (81%) received prior platinum therapy. Response: N= 1 unconfirmed PR (PR at 4 months (mo), POD at 6 mo), N= 4 stable disease (SD), N= 10 progressive disease (PD); N= 1 inevaluable (12 days of V only due to disease-related complications). Median PFS was 52 days (range 12 to 423). Three pts treated at 400mg V were dose-reduced for toxicity. Six pts had V related grade 3 toxicity including fatigue (N=3), hematologic (N=2) and nausea (N=1). No therapy-related grade 4-5 toxicities were observed. Conclusions: V was well tolerated. While no confirmed partial responses were observed, single-agent activity of V in previously treated PC was noted, and N= 4 (25%) remained on study with SD for ≥ 4mo (4, 6, 6, 9 mo). A randomized phase II trial evaluating cisplatin,gemcitabine +/- V is underway in untreated BRCA/PALB2mutPC (NCT01585805). Results of correlative studies will be presented. Acknowledgements: Lustgarten Foundation. NCI.AbbVie. Clinical trial information: NCT01585805.

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