7004 ORAL Phase II randomized, placebo controlled study of sorafenib in combination with dacarbazine in subjects with unresectable Stage III or 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.

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A Phase II Study of the Interleukin-6 Receptor Inhibitor Tocilizumab in Combination With Ipilimumab and Nivolumab in Patients With Unresectable Stage III or Stage IV Melanoma

Case Medical Research ◽

10.31525/ct1-nct03999749 ◽

2019 ◽

Author(s):

Keyword(s):

Phase Ii ◽

Interleukin 6 ◽

Phase Ii Study ◽

Stage Iv ◽

Stage Iii ◽

Unresectable Stage ◽

Interleukin 6 Receptor ◽

Stage Iv Melanoma ◽

Receptor Inhibitor

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Peripheral and local predictive immune signatures identified in a phase II trial of ipilimumab with carboplatin/paclitaxel in unresectable stage III or stage IV melanoma

Journal for ImmunoTherapy of Cancer ◽

10.1186/s40425-017-0290-x ◽

2017 ◽

Vol 5 (1) ◽

Cited By ~ 22

Author(s):

Rahima Jamal ◽

Réjean Lapointe ◽

Eftihia Cocolakis ◽

Paméla Thébault ◽

Shirin Kazemi ◽

...

Keyword(s):

Phase Ii ◽

Phase Ii Trial ◽

Stage Iv ◽

Stage Iii ◽

Immune Signatures ◽

Unresectable Stage ◽

Stage Iv Melanoma

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A phase II trial of nab-paclitaxel (ABI-007) and carboplatin in patients with unresectable stage IV melanoma

Cancer ◽

10.1002/cncr.25659 ◽

2010 ◽

Vol 117 (8) ◽

pp. 1704-1710 ◽

Cited By ~ 65

Author(s):

Lisa A. Kottschade ◽

Vera J. Suman ◽

Thomas Amatruda ◽

Robert R. McWilliams ◽

Bassam I. Mattar ◽

...

Keyword(s):

Phase Ii ◽

Phase Ii Trial ◽

Stage Iv ◽

Unresectable Stage ◽

Stage Iv Melanoma

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Phase II trial of carboplatin, weekly paclitaxel, and biweekly bevacizumab in patients with unresectable stage IV melanoma

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.8560 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 8560-8560 ◽

Cited By ~ 3

Author(s):

D. G. Perez ◽

V. Suman ◽

T. Amatruda ◽

M. Gornet ◽

R. Morton ◽

...

Keyword(s):

Phase Ii ◽

Performance Status ◽

Stage Iv ◽

Progression Free Survival ◽

Uncontrolled Hypertension ◽

Unresectable Stage ◽

Full Study ◽

Grade 3 ◽

Endothelial Growth Factor ◽

Stage Iv Melanoma

8560 Background: In patients with metastatic melanoma, the combination of chemotherapy with an agent that specifically targets vascular endothelial growth factor (VEGF) might be able to control tumor growth and progression much more effectively than chemotherapy alone. Methods: A two-stage phase II clinical trial was conducted in patients with unresectable stage IV melanoma to assess the anti-tumor activity and toxicity profile of the combination of paclitaxel (80 mg/m2 IV on days 1, 8 and 15 of a 28-day cycle), carboplatin (AUC = 6 IV on day 1) and bevacizumab (10 mg/kg IV on days 1 and 15). The primary end point of the study was the 8-week progression-free survival rate (PFS). Enrollment to the second stage of the study was opened if 8 or more of the first 20 patients enrolled remained progression-free at 8 weeks. Eligible patients had measurable disease by RECIST criteria, a performance status (PS) of 0–2 and acceptable pre-registration organ function. Exclusion criteria included: brain metastases, significant recent bleeding, uncontrolled hypertension and ongoing anticoagulation. The study opened in February 2006 and completed full study accrual in August 2006. Data from the 20 patients enrolled in the first stage are presented here. Results: Patients (60% male) had a median age of 63 and had a good performance status (85% had PS of 0). M1c disease was present in 45% of patients and 35% had undergone previous chemotherapy for stage IV melanoma (50% prior immunotherapy). Only 6 patients did not complete more than 2 cycles of chemotherapy due to refusal (3), desire for alternative treatment (1) or progression (2). Median follow-up among the 15 patients still alive was 5.5 months (range: 6 weeks - 9 months). The 8-week PFS rate was 70% (14/20). The median time to progression was 163 days. One partial response was observed. There were 3 disease-related deaths at 65, 120 and 190 days post-registration. The most common toxicities were neutropenia (95%; 45% = grade 3), anemia (95%; 15% = grade 3), fatigue (90%; 5% = grade 3), leukopenia (85%; 25% = grade 3), and thrombocytopenia (75%; 5% = grade 3). Conclusions: The combination of paclitaxel, carboplatin and bevacizumab appears to be well tolerated and clinically active in patients with stage IV melanoma. No significant financial relationships to disclose.

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

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.9028 ◽

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]

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