A first-line, phase II study with dacarbazine (DTIC) plus thymosin alpha 1 (Ta1) with or without interferon alpha (IFNa) vs. DTIC plus IFNa in stage IV melanoma

2006 ◽  
Vol 16 (Supplement 1) ◽  
pp. S39
Author(s):  
A. Mackiewicz ◽  
A. Testori ◽  
V. Ferraresi ◽  
M. Maio ◽  
C. Garbe ◽  
...  
Keyword(s):  
Interferon Alpha ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Stage Iv ◽  
First Line ◽  
Thymosin Alpha 1 ◽  
Stage Iv Melanoma

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]

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.

A large first-line, randomized, dose-finding, phase II study on thymosin-alpha 1 (T-alpha 1) plus dacarbazine (DTIC) with or without interferon-alpha (IFN-alpha) compared to DTIC plus IFN-alpha in stage IV melanoma. Tumor response and survival results

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8535-8535 ◽  
Author(s):  
R. Camerini ◽  
A. Mackiewicz ◽  
A. Testori ◽  
U. Trefzer ◽  
J. Jassem ◽  
...  
Keyword(s):  
T Cell ◽  
Null Hypothesis ◽  
Tumor Response ◽  
Stage Iv ◽  
Control Group ◽  
First Line ◽  
Ifn Alpha ◽  
Thymosin Alpha 1 ◽  
Melanoma Patients ◽  
Stage Iv Melanoma

8535 Background: Thymosin alpha 1 is an immunomodulatory compound that promotes T cell maturation and upregulates T cell response. Ta1 showed clinical potential benefit in a previous pilot study in melanoma patients. Methods: Phase II, randomized, stratified, open-study testing different doses of Ta1 in association with DTIC and IFNa, as first-line therapy in stage IV melanoma patients (AJCC 2001) without brain metastases. The primary endpoint is tumor response and secondary overall survival. Four arms were initially planned: DTIC + IFNa + 1.6 or 3.2 mg Ta1, DTIC + 3.2 mg Ta1, and DTIC + IFNa (control group). A dose-response effect in a preliminary analysis on 142 patients led to the addition of a fifth arm with DTIC + IFNa + 6.4 mg Ta1. Ninety-five patients were allocated to each arm to test the hypothesis that P0 = 0.05 vs the alternative hypothesis that P1 = 0.15 (alpha = 5%, within-group statistical analysis, power = 95%). The five groups were analyzed independently one from the other, nine responses representing the minimal threshold for rejecting the null hypothesis Patients received DTIC (800 mg/m2) iv on day 1, Ta1 (1.6, 3.2 or 6.4 mg) sc on days 8–11 and 15–18, and IFNa (3 MIU) sc on days 11 and 18 during 28d cycles. Tumor response was evaluated every two cycles according to RECIST criteria, utilizing a central review. Results: Data of 483 pts (62% M1c; 25% M1b; 13% M1a) from 64 European sites are given in the table . Thirteen and 10 confirmed responses were observed for the DTIC+ 3.2 mg Ta1 and DTIC+ IFNa + 3.2 mg Ta1 arms (vs 5 in the control group) thus rejecting the null hypothesis that P0 = 0.05. No additional toxicity with the addition of Ta1 was observed. Conclusions: These results suggest a potential survival advantage with the addition of Ta1 to ‘standard‘ treatment of stage IV melanoma patients. The role of Interferon alpha in this therapeutic association is debatable. [Table: see text] [Table: see text]

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

scholarly journals P77.05 Phase II Study of Imprime PGG and Pembrolizumab in Stage IV NSCLC After Progression on First-Line Therapy: BTCRC-LUN15-017

2021 ◽  
Vol 16 (3) ◽  
pp. S637
Author(s):  
E. Sisel ◽  
M. Furqan ◽  
J. Malhotra ◽  
A. Shergill ◽  
K. Kennedy ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Stage Iv ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

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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