Active immunization toward the MAGE-A3 antigen in patients with metastatic melanoma: Four-year follow-up results from a randomized phase II study (EORTC16032-18031).

2011 ◽  
Vol 29 (15_suppl) ◽  
pp. 8535-8535 ◽  
Author(s):  
W. Kruit ◽  
S. Suciu ◽  
B. Dreno ◽  
V. Chiarion-Sileni ◽  
L. Mortier ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Active Immunization ◽  
Randomized Phase Ii

Randomized phase II study of 6 versus 12 months of adjuvant imatinib for patients with intermediate- or high-risk GIST.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 9-9
Author(s):  
Kazuya Muguruma ◽  
Yukinori Kurokawa ◽  
Toshimasa Tsujinaka ◽  
Junya Fujita ◽  
Takuya Nakai ◽  
...  
Keyword(s):  
High Risk ◽  
Phase Ii ◽  
Interim Analysis ◽  
Phase Ii Study ◽  
Hazard Ratio ◽  
P Value ◽  
Adjuvant Imatinib ◽  
Randomized Phase Ii ◽  
Ecog Ps

9 Background: The Z9001 study revealed adjuvant imatinib for 1 year significantly improved RFS in GIST patients (pts). The SSGXVIII study compared 3 years with 1 year of adjuvant imatinib for high risk GIST pts, but there was no study to evaluate shorter period of imatinib administration than 1 year. We conducted a randomized phase II study to compare 6 months (6-mo) with 12 months (12-mo) adjuvant imatinib for intermediate or high risk GIST pts. Methods: Inclusion criteria included ECOG-PS of 0 or 1, age between 20 and 79 years, and primary KIT-positive GIST with intermediate or high risk according to the Fletcher criteria. Pts were randomized assigned to the 6-mo or 12-mo treatment of imatinib 400 mg/day after complete resection. The primary endpoint was recurrence-free survival (RFS). The study was designed as a randomized screening trial to evaluate non-inferiority with margin of hazard ratio 1.67, 1-sided alpha 0.2 and power 0.8. Results: Ninety-two pts were randomly allocated the 6-mo group (n=45) or the 12-mo group (n=47) between Dec 2007 and Aug 2011, which was well balanced for baseline characteristics. One patient was ineligible due to non-GIST (desmoid) tumor at a central review. The proportions of pts completed their assigned adjuvant treatment were 80% in the 6-mo and 70% in the 12-mo group. The first interim analysis was conducted at Sep 2012 with the median follow-up time of 33 months. The 1- and 2-year RFS were 82% and 65% in the 6-mo group and 96% and 86% in the 12-mo group, respectively. Hazard ratio of recurrence was 1.81 (95%CI: 0.84-3.91), and the 2-sided log-rank p value was 0.12. Adjuvant imatinib was well tolerated, with one patient of Gr. 4 rash and no treatment-related death. Because of the lower efficacy of the 6-mo group than expected, the Data and Safety Monitoring Committee recommended the early release of first interim analysis results. Conclusions: Adjuvant Imatinib for 6-mo was inferior in efficacy to that for 12-mo in terms of RFS. Shortening of the adjuvant imatinib duration is not recommended for intermediate or high risk GIST pts. Clinical trial information: UMIN000000950.

A randomized phase II study of vemurafenib plus cobimetinib continuous versus intermittent in previously untreated BRAF V600-mutation positive patients with unresectable locally advanced or metastatic melanoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS9599-TPS9599 ◽  
Author(s):  
Jose A. Lopez-Martin ◽  
Alfonso Berrocal ◽  
María González-Cao
Keyword(s):  
Metastatic Melanoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Mapk Pathway ◽  
Locally Advanced ◽  
Advanced Melanoma ◽  
Drug Resistant ◽  
Randomized Phase Ii ◽  
Melanoma Patients ◽  
Resistant Cells

TPS9599 Background: Previous clinical trials have shown that vemurafenib significantly increases PFS and OS in untreated BRAFV600 mutant advanced melanoma patients. Nevertheless, disease progression occurs after a median of 6-7 months since start of vemurafenib. Several mechanisms of acquired resistance to vemurafenib result in reactivation of MAPK pathway. Upfront addition of a MEK inhibitor (MEKi) to vemurafenib delays secondary resistance to BRAFi. The combination of cobimetinib, a MEKi, plus vemurafenib as a continuous administration was approved by FDA in 2,015 in untreated metastatic BRAFV600 advanced melanoma patients based on an increase in PFS and OS achieved in a phase III trial (coBRIM trial). Preclinical models have shown that continuous vemurafenib dosing promotes the clonal expansion of drug-resistant cells, and intermittent dosing could serve to eliminate the fitness advantage of the resistant cells and delay the onset of drug-resistant disease (Das Thakur, Nature 2013). These observations and some clinical case reports support upfront evaluation of alternative dosing regimens of MAPK pathway inhibition. Methods: This is a randomized phase II study to explore the efficacy and safety of two schedules of administration of vemurafenib in combination with cobimetinib (continuous – 28-day cycles with vemurafenib 960 mg PO BID, Days 1-28, and cobimetinib 60 mg PO QD, Days 1-21 – and intermittent – same dose/schedule during first 12 weeks, and then, same doses with the following schedule: vemurafenib 4 weeks on /2 weeks off, and cobimetinib 3 weeks on/ 3 weeks off), in patients with untreated, BRAFV600 mutated, unresectable, measurable (RECIST 1.1), locally advanced or metastatic melanoma. Prior adjuvant immunotherapy is allowed. Primary endpoint is PFS. Secondary endpoints include: OS, ORR, pharmacokinetic and pharmacodynamic profiles and safety. Additional translational research to analyze predictive factors and mechanism of resistance will be explored. The trial is in progress; 56 of up to 116 planned pts have been recruited at the end of December 2016 (enrollment started in June 2015). Clinical trial information: NCT02583516.

Single-dose radiotherapy (SDRT) in the management of intermediate risk prostate cancer: Early results from a phase II randomized trial.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 128-128 ◽  
Author(s):  
Carlo Greco ◽  
Nuno Pimentel ◽  
Oriol Pares ◽  
Vasco Louro ◽  
Zvi Y. Fuks
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Foley Catheter ◽  
Prostate Gland ◽  
Intermediate Risk ◽  
Time Motion ◽  
Early Results ◽  
Randomized Phase Ii ◽  
Patient Reported

128 Background: To report initial response, acute treatment-related toxicity and patient-reported quality of life (QoL) after 24Gy SDRT derived from a randomized Phase II study of patients with intermediate-risk adenocarcinoma of the prostate (NCCN definition). Methods: Between November 2015 and December 2016, 30 hormone-naïve patients were enrolled in an IRB-approved prospectively randomized phase II study to receive either 45Gy in 5 consecutive daily fractions (Hypo-SBRT) or 24Gy SDRT. Treatment was based on VMAT-IGRT with urethral sparing via a dose-painting technique and real-time motion management with beacon transponders. The PTV included the MR-delineated prostate gland and seminal vesicles with 2 mm margin. Precise PTV targeting and anatomical reproducibility was achieved via placement of an endorectal air-filled balloon (150 cc) and a Foley catheter. This setup also conferred organ motion mitigation, and online tracking ensured treatment delivery within the 2 mm PTV margin.. Genito-urinary (GU) and gastro-intestinal (GI) toxicity were graded according to the NCI CTCAE v.4, and QoL was assessed by EPIC and IPSS questionnaires. Tumor response was assessed biochemically (PSA) and by follow-up MRI at 3 months after treatment and at 6 months intervals thereafter. Results: With a median follow-up of 16 months (range, 11-24), no grade ≥2 acute GI or GU toxicities were observed in either group. There were no significant differences in mean EPIC scores in all domains. An initial 6% and 8% drop in the EPIC urinary domain score occurred in the hypo and SDRT arm respectively, returning to baselines by 3 months. . PSA reduction kinetics were similar between the two regimens, reaching ≤1 ng/mL by 18 months. Of note, all cases, regardless of treatment regimen, converted to non-detectable disease on MRI at 6 months. Patients in this trial will receive a planned 24 months post-treatment biopsy to validate treatment outcome. Conclusions: These early trial outcomes indicate that 24Gy SDRT can be consistently and safely delivered, yielding the same low acute toxicity as demonstrated with the hypo 5x9Gy schedule, and is associated with excellent QoL measures. Clinical trial information: NCT02570919.

scholarly journals A randomized phase II study of cilengitide (EMD 121974) in patients with metastatic melanoma

2012 ◽  
Vol 22 (4) ◽  
pp. 294-301 ◽  
Author(s):  
Kevin B. Kim ◽  
Victor Prieto ◽  
Richard W. Joseph ◽  
Abdul H. Diwan ◽  
Gary E. Gallick ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Randomized Phase Ii

Randomized phase II study of concurrent and sequential combinations of rituximab (R) plus CHOP (R-CHOP) in untreated indolent B-NHL: 7-year follow-up results

2008 ◽  
Vol 26 (15_suppl) ◽  
pp. 8616-8616 ◽  
Author(s):  
K. Itoh ◽  
T. Igarashi ◽  
M. Ogura ◽  
Y. Morishima ◽  
T. Hotta ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Randomized Phase Ii

scholarly journals BEAM: A Randomized Phase II Study Evaluating the Activity of Bevacizumab in Combination With Carboplatin Plus Paclitaxel in Patients With Previously Untreated Advanced Melanoma

2012 ◽  
Vol 30 (1) ◽  
pp. 34-41 ◽  
Author(s):  
Kevin B. Kim ◽  
Jeffrey A. Sosman ◽  
John P. Fruehauf ◽  
Gerald P. Linette ◽  
Svetomir N. Markovic ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Elevated Serum ◽  
Serum Lactate ◽  
Primary Objective ◽  
Phase Iii ◽  
Serum Lactate Dehydrogenase ◽  
Double Blind

Purpose Metastatic melanoma, a highly vascularized tumor with strong expression of vascular endothelial growth factor, has an overall poor prognosis. We conducted a placebo-controlled, double-blind phase II study of carboplatin plus paclitaxel with or without bevacizumab in patients with previously untreated metastatic melanoma. Patients and Methods Patients were randomly assigned in a two-to-one ratio to carboplatin (area under the curve, 5) plus paclitaxel (175 mg/m2) and bevacizumab (15 mg/kg; CPB) or placebo (CP) administered intravenously once every 3 weeks. Progression-free survival (PFS) was the primary end point. Secondary end points included overall survival (OS) and safety. Results Two hundred fourteen patients (73% with M1c disease) were randomly assigned. With a median follow-up of 13 months, median PFS was 4.2 months for the CP arm (n = 71) and 5.6 months for the CPB arm (n = 143; hazard ratio [HR], 0.78; P = .1414). Overall response rates were 16.4% and 25.5%, respectively (P = .1577). With 13-month follow-up, median OS was 8.6 months in the CP arm versus 12.3 months in the CPB arm (HR, 0.67; P = .0366), whereas in an evaluation 4 months later, it was 9.2 versus 12.3 months, respectively (HR, 0.79; P = .1916). In patients with elevated serum lactate dehydrogenase (n = 84), median PFS and OS were longer in the CPB arm (PFS: 4.4 v 2.7 months; HR, 0.62; OS: 8.5 v 7.5 months; HR, 0.52). No new safety signals were observed. Conclusion The study did not meet the primary objective of statistically significant improvement in PFS with the addition of bevacizumab to carboplatin plus paclitaxel. A larger phase III study will be necessary to determine whether there is benefit to the addition of bevacizumab to carboplatin plus paclitaxel in this disease setting.

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