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

1999 ◽  
Vol 17 (9) ◽  
pp. 2762-2762 ◽  
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.

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

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7001-7001 ◽  
Author(s):  
M. A. Socinski ◽  
S. Novello ◽  
J. M. Sanchez ◽  
J. A. Brahmer ◽  
R. Govindan ◽  
...  
Keyword(s):  
Phase Ii ◽  
Survival Data ◽  
Kinase Inhibitor ◽  
Phase Ii Trial ◽  
Single Agent ◽  
Pulmonary Hemorrhage ◽  
Open Label ◽  
Initial Report ◽  
Multicenter Phase ◽  
Previously Treated

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]

795 A multicenter phase II trial (SWOG S1609, cohort 51) of ipilimumab and nivolumab in metastatic or unresectable angiosarcoma: a substudy of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART)

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A843-A843
Author(s):  
Michael Wagner ◽  
Megan Othus ◽  
Sandip Patel ◽  
Christopher Ryan ◽  
Ashish Sangal ◽  
...  
Keyword(s):  
Phase Ii ◽  
Immune Checkpoint ◽  
Uv Light ◽  
Light Exposure ◽  
Case Reports ◽  
Objective Response ◽  
Open Label ◽  
Primary Tumors ◽  
Multicenter Phase ◽  
Grade 3

BackgroundAngiosarcoma is a rare cancer of endothelial cells that can be aggressive and carries a high mortality. A subset of angiosarcomas are characterized by high tumor mutational burden (TMB) and UV light exposure DNA mutational signature. Isolated case reports have suggested clinical efficacy of immune checkpoint blockade in angiosarcoma; no prospective studies of immune checkpoint inhibition in angiosarcoma have been reported. We report efficacy analysis results for patients with advanced or unresectable angiosarcoma treated with ipilimumab and nivolumab as a cohort of an ongoing phase II study for rare cancers (NCT02834013).MethodsThis is a prospective, open-label, multicenter phase II clinical trial of ipilimumab (1mg/kg IV q6weeks) plus nivolumab (240mg IV q2weeks) for patients with metastatic or unresectable angiosarcoma. Primary endpoint is objective response rate as assessed by RECIST v1.1, including measurable cutaneous disease that can be followed by photography. Secondary endpoints include PFS, OS, stable disease at six months, and toxicity. A two-stage design is used with six patients in the first stage and an additional ten patients in the second stage.ResultsAt data cutoff, 16 patients with angiosarcoma were enrolled. Median age was 68 years (25-81 years). Median number of prior lines of therapy was 2 (0-5). 9 patients had cutaneous primary tumors of any cutaneous site, 7 had non-cutaneous primary tumors. ORR for all patients was 25% (4/16, table 1, figure 1). Subgroup analysis revealed that 60% (3/5) of patients with primary cutaneous tumors of the scalp or face had a confirmed objective response. 6-month PFS was 38%. 75% of patients experienced an adverse event (AE), and 25% experienced a grade 3-4 AE. 68.8% experienced an immune related AE (irAE), and 2 (12.5%) developed grade 3 or 4 irAEs. Grade 3-4 irAEs were ALT and AST increase and diarrhea. There were no grade 5 toxicities.ConclusionsThe combination of ipilimumab and nivolumab was well tolerated and had an ORR of 25% in angiosarcoma regardless of primary site, with 3 of 5 patients with cutaneous tumors of the scalp or face responding. Ipilimumab and nivolumab warrant further investigation in angiosarcoma.AcknowledgementsFunding: National Institutes of Health/National Cancer Institute grant awards CA180888, CA180819, CA180868; and in part by Bristol-Myers Squibb CompanyTrial RegistrationNCT02834013Ethics ApprovalThis study was approved by the NCI CIRB.

Regomune: A phase II study of regorafenib + avelumab in solid tumors—Results of the biliary tract cancer (BTC) cohort.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4096-4096
Author(s):  
Sophie Cousin ◽  
Carine A. Bellera ◽  
Jean Philippe Guégan ◽  
Thibault Mazard ◽  
Carlos A. Gomez-Roca ◽  
...  
Keyword(s):  
Phase Ii ◽  
Adaptive Design ◽  
Objective Response ◽  
Locally Advanced ◽  
Survival Rates ◽  
Previous Treatment ◽  
Progression Free Survival ◽  
Treatment Interruption ◽  
Clinical Activity ◽  
Open Label

4096 Background: Regorafenib (R) has shown promising efficacy in patients (pts) with BTC refractory to standard chemotherapy. Anti-PD1/PD-L1 antibodies have only limited clinical activity. Synergy between R and anti–PD-1/PD-L1 antibodies has been shown in pre-clinical solid tumor models. Methods: This is a single-arm open-label multicentric phase II trial (Bayesian adaptive design) assessing the efficacy and safety of R (160 mg QD 3weeks/4) + avelumab (A) (10 mg/kg every 2 weeks) combination in BTC pts. The primary endpoint was the objective response rate under treatment, based on central review according to RECIST 1.1. Secondary endpoints included: 1-year progression free survival (PFS), 1-year overall survival (OS), and Safety using NCI-CTCAE v5.0. Correlative studies were planned from pts tumor samples obtained at baseline. Results: Between Nov. 2018 and Nov. 2019, 34 BTC pts were enrolled in 4 centers. Median age was 63 (range 36 – 80). Median follow-up was 9.8 months. Median number of previous treatment lines for metastatic or locally advanced disease was: 2 (range 1 – 4). Twenty-nine (85.3%) pts experienced at least 1 dose modification or treatment interruption of R or A due to an adverse event (AE) related to the treatment. The most common grade 3/4 AEs were : Hypertension (17.6%), Fatigue (14.7%), and maculo-papular rash (11.8%). No death was related to the treatment. Among the 29 pts with at least one imaging tumor assessment, 4 (13.8%) achieved a partial response, and 11 (37.9%) demonstrated stable disease including 10 (34.5%) pts with tumor shrinkage. Fourteen pts (48.3%) had progressive disease. The median PFS and OS were 2.5 months (95%CI 1.9 – 5.5) and 11.9 months (95%CI 6.2 – NA) respectively. Baseline tumor samples were available for 27 pts. High IDO and PD-L1 expression at baseline was associated with better outcome. Conclusions: The R+A combination is associated with significant anti-tumor activity with promising survival rates in this heavily pre-treated population. Full Biomarkers analyses will be presented at the meeting. Clinical trial information: NCT03475953.

An open-label, multicenter phase II trial of capecitabine in patients with cisplatin-refractory or relapsed germ cell tumors

2007 ◽  
Vol 18 (3) ◽  
pp. 273-276 ◽  
Author(s):  
Karin Oechsle ◽  
Friedemann Honecker ◽  
Christian Kollmannsberger ◽  
Oliver Rick ◽  
Victor Gr??nwald ◽  
...  
Keyword(s):  
Germ Cell ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Germ Cell Tumors ◽  
Open Label ◽  
Multicenter Phase

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

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7707-7707 ◽  
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.

Gemcitabine and oxaliplatin (GEMOX) alone or in combination with cetuximab as first-line treatment for advanced biliary cancer: Final analysis of a randomized phase II trial (BINGO).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4032-4032 ◽  
Author(s):  
David Malka ◽  
Laetitia Fartoux ◽  
Vanessa Rousseau ◽  
Tanja Trarbach ◽  
Eveline Boucher ◽  
...  
Keyword(s):  
Phase Ii ◽  
Primary Endpoint ◽  
Mutational Analysis ◽  
Metabolic Response ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Objective Response ◽  
First Line ◽  
Open Label ◽  
Randomized Phase Ii

4032 Background: Gemcitabine-platinum chemotherapy (CTx) regimens are widely accepted as first-line standard of care for patients (pts) with advanced biliary cancers (ABC). EGFR overexpression has been observed in ABC, suggesting that the combination with anti-EGFR monoclonal antibodies may be appropriate. Methods: Patients with ABC, WHO performance status (PS) 0-1, and without prior palliative CTx were eligible for this international, open-label, two-stage, non-comparative, randomized phase II trial. Patients received GEMOX (gemcitabine, 1 g/m² [10 mg/m²/min] at day [D]1 + oxaliplatin, 100 mg/m² at D2, arm A) or GEMOX + cetuximab (500 mg/m² at D1 or 2, arm B), every 2 weeks. The primary endpoint was crude 4-month progression-free survival (PFS) rate (H0, <40%; H1, ≥60%; planned sample size, 100 pts, increased to 150 pts by amendment to allow subgroup analyses). Secondary endpoints were objective response rate (ORR), disease control rate (DCR), PFS, overall survival (OS), and toxicity (NCI-CTC v3.0). Exploratory endpoints included early metabolic response as assessed by PET at 1 month, and tumor KRAS mutational analysis. Results: From Oct. 2007 to Dec. 2009, we enrolled 150 pts (median age, 62 years; male, 57%; metastatic, 79%; cholangiocarcinoma, 84%; median follow-up, 30 months) (Table). Conclusions: GEMOX-cetuximab regimen was well tolerated and met its primary endpoint (4-month PFS ≥60%). However, median PFS and OS were similar in both arms. Exploratory analyses (e.g., KRAS tumor status) are underway to identify pt subgroups deriving benefit from the addition of cetuximab to CTx. [Table: see text]

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