Phase II study of aflibercept (VEGF trap) in recurrent inoperable stage III or stage IV melanoma of cutaneous or ocular origin

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9028-9028
Author(s):  
A. A. Tarhini ◽  
S. Christensen ◽  
P. Frankel ◽  
K. Margolin ◽  
C. Ruel ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Angiogenesis Inhibitor ◽  
Stage Iv ◽  
Left Ventricular Diastolic Dysfunction ◽  
Left Ventricular ◽  
Stage Iii ◽  
Unknown Primary ◽  
Vegf Receptor ◽  
Stage Iv Melanoma

9028 Background: Aflibercept is a fusion protein combining the Fc portion of human IgG1with the extracellular ligand-binding domains of human VEGFR1 and VEGFR2, acting as a high-affinity soluble VEGF receptor and potent angiogenesis inhibitor. Methods: Phase II study of aflibercept in patients with inoperable stage III or IV melanoma who had received no prior chemotherapy or hormonal therapy. A 2-stage design was adopted focusing upon response rate (RECIST) and 4-month PFS rate. First stage accrual of 21 patients was specified, while final accrual of 41 is planned, with adequate response/4 month PFSR. Aflibercept was given at 4 mg/kg IV every 2 weeks. Response was assessed every 8 weeks. Results: Twenty seven patients (16 male, 11 female), age 23–83 (median 58) have been enrolled to date. All had AJCC stage IV melanoma (3M1a, 3M1b, 21M1c). Karnofsky PS: 100 (13), 90 (11) or 80 (3). Nine patients had primary ocular melanoma, 16 cutaneous and 2 unknown primary site. A total of 160 cycles have been administered (median 4; range 1–18). Grade 3/4 toxicities included cerebral ischemia (1 patient; 4%), confusion (1; 4%), thrombocytopenia (1; 4%), hypertension (7; 26%), hypotension (1; 4%), left ventricular diastolic dysfunction (1; 4%), fatigue (1; 4%), proteinuria (4; 15%), extraocular muscle paresis (1; 4%), renal failure (1; 4%), back pain (1; 4%), headache (1; 4%). Interim analysis was conducted after the first 21 patients (stage 1). Eight (1 M1a, 1M1b, 6M1c; 4 ocular, 3 cutaneous, 1 unknown primary) of the first 21 patients had at least 4 months of PFS (10 out of 27; 2 additional patients with cutaneous melanoma had SD: 1M1a and 1M1c). One patient (23rd; cutaneous, M1c) had a confirmed complete remission. Four patients were taken off study prior to response evaluation for toxicity (3) or treatment refusal (1). One patient is currently disease free who was not evaluable for response (previous surgery and radiofrequency ablation of measurable disease site). Eleven patients had progression. Conclusions: Aflibercept can be administered with acceptable toxicity, and exhibits promising antitumor efficacy against advanced melanoma. This study continues second stage accrual with anticipated closure before June 2009. [Table: see text]

Paclitaxel/carboplatin with or without sorafenib in the first-line treatment of patients with stage III/IV epithelial ovarian cancer: A randomized phase II study of the Sarah Cannon Research Institute.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5513-5513
Author(s):  
Dana Shelton Thompson ◽  
B. Stephens Dudley ◽  
John A. Bismayer ◽  
Victor G. Gian ◽  
William McIver Merritt ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Ovarian Carcinoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Single Agent ◽  
Angiogenesis Inhibitor ◽  
Stage Iii ◽  
Vegf Receptor ◽  
First Line ◽  
Randomized Phase Ii

5513 Background: The combination of paclitaxel and carboplatin is the most widely used chemotherapy regimen for patients (pts) with advanced ovarian cancer, producing a median survival of approximately 36 months. Recently, the addition of bevacizumab, an angiogenesis inhibitor, has improved progression-free survival (PFS) when compared to paclitaxel/carboplatin alone. Sorafenib is an oral multi-kinase inhibitor with effects on tumor angiogenesis through inhibition of the VEGF receptor. The purpose of this randomized phase II study was to compare efficacy of paclitaxel/carboplatin with and without sorafenib. Methods: Women with histologically confirmed, maximally debulked, previously untreated stage III/IV epithelial ovarian carcinoma were randomized to receive paclitaxel 175 mg/m2and carboplatin AUC 6 (PC) or PC + sorafenib 400 mg PO BID (S). All patients received 6 cycles, given every 3 weeks; pts receiving PC+S continued single agent sorafenib for 52 weeks total. The primary endpoint was 2-year PFS rate. Results: 85 pts were randomized between 1/07 and 10/11 (PC+S 43; PC 42). Pt characteristics were similar between groups, except that more patients with only CA125 elevation received PC+S (65% vs 43%). Overall, 67 pts (79%) completed 6 cycles of chemotherapy (PC+S 74%; PC 83%). More patients stopped PC+S due to toxicity (14% vs 7%). 22 pts (51%) receiving PC+S began single agent S after 6 cycles PC, and 12 pts (28%) completed 52 weeks of S. There was no difference in the 2-year PFS rates: PC+S 40%, PC 39%. Overall survival comparisons were also similar (p = 0.36). Pts receiving PC+S had more grade 3 rash (33% vs 0%) and hand-foot syndrome (9% vs 0%). Conclusions: The addition of sorafenib did not improve the efficacy of standard first-line PC in pts with stage III/IV ovarian carcinoma, and resulted in additional toxicity. Clinical trial information: NCT00390611.

A phase II single arm study of pazopanib and paclitaxel as first-line treatment for unresectable stage III and stage IV melanoma: Interim analysis.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8524-8524 ◽  
Author(s):  
John P. Fruehauf ◽  
Beverly Alger ◽  
Basmina Parmakhtiar ◽  
James G. Jakowatz ◽  
Claudette Bettis ◽  
...  
Keyword(s):  
Phase Ii ◽  
Interim Analysis ◽  
Cell Cancer ◽  
Stage Iv ◽  
Stage Iii ◽  
First Line ◽  
Open Label ◽  
Unresectable Stage ◽  
Biomarker Analysis ◽  
Stage Iv Melanoma

8524 Background: Metastatic melanoma lacks effective therapy. Pazopanib is a small-molecule inhibitor of VEGFR-1,2,3, PDGFR-B and c-KIT that has antiangiogenic activity in renal cell cancer as well as inhibition of melanoma tumor xenografts. We designed a phase II single arm, open label clinical trial evaluating pazopanib in combination with metronomic paclitaxel as first line therapy for subjects with unresectable stage III and stage IV melanoma. Methods: This protocol utilizes a Simon 2-stage Minimax design, with a planned interim analysis to confirm >3 responders to move to the second stage. To date, 20 eligible patients have been enrolled with 17 evaluable for response. All subjects were treatment naïve and received paclitaxel at 80mg/m2 weekly for three weeks in a 4 week cycle and pazopanib at 800mg as a continuous daily oral dose. The primary endpoint is 6 month progression free survival. Exploratory endpoints include biomarker analysis that may be associated with treatment outcomes (serum VEGF, soluble VEGF R2, serum HIF, serum TSP1 and BRAF mutation status). An additional exploratory endpoint includes the in vitro activity of pazopanib and paclitaxel on patient biopsy material co-cultured with vascular endothelial cells. RECIST criteria were used to define treatment response. Results: For the 17 evaluable patients treated to date the following results were seen: 1 CR, 6 PR’s, 8 SD’s and 2 PD’s. The overall RR (CR+PR) was 40%. Total disease control rate was 80% (PR+SD). The most common AEs/lab abnormalities were nausea (71%), hypertension (57%), fatigue (57%) and vomiting (43%). Grade 3-4 AEs included hypertension (28%), transaminitis (21%) and neutropenia (14%). One patient discontinued for grade 4 transaminitis which subsequently resolved completely. Dose reductions were required for pazopanib in 5 patients and for paclitaxel in one patient. Conclusions: Planned interim analysis of this phase II study demonstrated that pazopanib in combination with paclitaxel was well tolerated and resulted in a 40% response rate, indicating that this combination is of further interest. Accrual will continue to reach a goal of 60 patients.

Phase II study of taxotere/carboplatin with pharmacokinetics and -Dynamics In NSCLC for downstaging in stage III B and palliation in stage IV

1997 ◽  
Vol 33 ◽  
pp. S232 ◽  
Author(s):  
F. Griesinger ◽  
W. Kem ◽  
L. Binder ◽  
P. Hannemann ◽  
C.P. Criée ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Stage Iv ◽  
Stage Iii

Combined treatment with ipilimumab and intratumoral interleukin-2 in pretreated patients with stage IV melanoma—safety and efficacy in a phase II study

2016 ◽  
Vol 66 (4) ◽  
pp. 441-449 ◽  
Author(s):  
Benjamin Weide ◽  
Alexander Martens ◽  
Kilian Wistuba-Hamprecht ◽  
Henning Zelba ◽  
Ludwig Maier ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Combined Treatment ◽  
Interleukin 2 ◽  
Stage Iv ◽  
Safety And Efficacy ◽  
Pretreated Patients ◽  
Stage Iv Melanoma

A phase II study of dibromodulcitol (DBD) in Stage IV melanoma

1984 ◽  
Vol 7 (5) ◽  
pp. 555-556
Author(s):  
Judy Hopkins ◽  
Frederick Richards ◽  
Douglas Case ◽  
Ellen Pope ◽  
Don V. Jackson ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Stage Iv ◽  
Stage Iv Melanoma

Cisplatin, fluorouracil with leucovorin calcium enhancement, and synchronous accelerated radiotherapy in the management of locally advanced head and neck cancer: a phase II study.

1989 ◽  
Vol 7 (4) ◽  
pp. 471-476 ◽  
Author(s):  
T G Wendt ◽  
R C Hartenstein ◽  
T P Wustrow ◽  
J Lissner
Keyword(s):  
Head And Neck ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Locally Advanced ◽  
Stage Iv ◽  
Distant Metastases ◽  
Stage Iii ◽  
Limiting Factor ◽  
Accelerated Radiotherapy ◽  
Leucovorin Calcium

In a phase II study, patients with locally advanced squamous cell carcinoma of the head and neck were treated with simultaneous chemoradiotherapy. Treatment was divided into three courses. Chemotherapy consisted of cis-diamminedichloroplatinum (II) (cisplatin [cis-DDP]) 60 mg/m2 intravenously (IV), fluorouracil (5-FUra) 350 mg/m2 IV, and folinic acid (leucovorin calcium [FA]) 50 mg/m2 IV on day 2 as bolus, and 5-FUra 350 mg/m2 over 24 hours and FA 100 mg/m2 over 24 hours on days 2 through 5. Radiotherapy consisted of 23.4 Gy over nine days divided into 13 fractions of 1.8 Gy each delivered twice a day from day 3 through day 11. This regimen was repeated on days 22 and 44. Total radiation dose amounted to 70.2 Gy over 51 days. Between August 1984 and October 1986, 62 (modified AJCC stage III, four; IV A, eight; IV B, 50) consecutive patients were entered in the study. Three patients died during treatment due to tumor hemorrhage. Of 59 patients, 48 (81%) achieved a clinically complete response (cCR); 11 (19%) achieved a partial response (cPR). Mean follow-up of the surviving patients was 29+ (24 to 44) months. Actuarial 2-year survival probability is 52%, including three early deaths from tumor bleeding. Tumor and neck nodes control rates at 2 years were 92% for stage III and IV A patients and 65% for stage IV B patients. Patients with cCR had a significantly better 2-year tumor and neck nodes control probability compared with patients who achieved cPR after therapy (P less than .001). Six patients developed distant metastases. Overall toxicity was tolerable, mucositis particularly was not a limiting factor.

scholarly journals Randomized Phase II Study of IL-2 With or Without an Allogeneic Large Multivalent Immunogen Vaccine for the Treatment of Stage IV Melanoma

2014 ◽  
Vol 37 (3) ◽  
pp. 261-265 ◽  
Author(s):  
Gautam Jha ◽  
Jeffrey S. Miller ◽  
Julie M. Curtsinger ◽  
Yan Zhang ◽  
Mathew F. Mescher ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Stage Iv ◽  
Randomized Phase Ii ◽  
Stage Iv Melanoma

Phase II study of docetaxel and vinorelbine plus GM-CSF in malignant melanoma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 18017-18017
Author(s):  
J. P. Fruehauf ◽  
K. M. Kong ◽  
J. G. Jakowatz
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Stage Iv ◽  
Synergistic Activity ◽  
Time To Progression ◽  
Proc Asco ◽  
Lung Cancer Patients ◽  
Gm Csf ◽  
Melanoma Patients ◽  
Stage Iv Melanoma

18017 Background: Patients having locoregional or metastatic melanoma have a poor prognosis, with 50% to 10% of patients dying from the disease within 5 years. Current chemotherapy regimens offer limited benefits to these patients and more effective and less toxic treatments are needed. Methods: We developed a phase II clinical trial to evaluate the activity of an every two week schedule of docetaxel (40mg/m2, d1), vinorelbine (30 mg/m2, d1) IV and sargramostim (GMCSF, 250 ug/m2 sq d2–11). This regimen was developed based on preclinical synergistic activity of paclitaxel plus vinorelbine (Neale et al. Melanoma Res 11:601, 2001), and evidence that the docetaxel plus vinorelbine combination can be given safely to lung cancer patients (Sanchez et al. Lung Ca 38:309, 2002). Sargramostim was included based on preliminary clinical data that it delays time to progression in stage IV melanoma patients resected for cure (Spitler, JCO 18:1614, 2000). We report here an interim analysis for the initial 21 patients with stage IV melanoma treated in first or second line. Results: The primary endpoint was time to progression. Grade III/IV toxicities included anemia (12.5%) and neutropenia (5%), with one patient requiring 25% dose reduction. To date, median time to progression (TTP) is 7 months, with 30% of cases showing greater than 8 months TTP. Conclusions: This result compares favorably with biochemotherapy, which has a median TTP of 5 months and overall survival of 8.4 months (Atkins Proc ASCO 22:708. 2003), while being significantly less toxic. Based on these favorable findings, we are continuing to accrue patients to this trial. [Table: see text]

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