scholarly journals P14.120 Phase II study of weekly carboplatin in pretreated adult malignant gliomas

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii97-iii97
Author(s):  
V Villani ◽  
A Pace ◽  
A Vidiri ◽  
A Tanzilli ◽  
F Sperati ◽  
...  
Keyword(s):  
Malignant Glioma ◽  
Phase Ii ◽  
Clinical Benefit ◽  
Phase Ii Study ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Single Agent ◽  
Malignant Gliomas ◽  
Recurrent Malignant Glioma ◽  
Eligibility Criteria

Abstract BACKGROUND Patients with relapse of recurrent glioma have a poor outcome and limited treatment options. The aim of this study is to investigate the clinical benefit and tolerability of weekly intravenous administration of carboplatin-based monotherapy in adult glioma patients who had progressed from previous chemotherapy lines based on temozolomide and nitrosoureas MATERIAL AND METHODS This was a single arm, Phase II study. Eligibility criteria included progressive or recurrent malignant glioma after radiotherapy and chemotherapy-based treatments and Karnofsky Performance Status (KPS) > 60. RESULTS Thirty-two patients (median age: 43.5 y) were enrolled to receive weekly carboplatin monotherapy in intravenous mode of administration. The median duration of response was 7.3 months with an overall disease control rate of 31.3%. Median progression-free survival (PFS) was 2.3 months while overall survival (OS) was 5.5 months. Patients achieving clinical benefit exhibited a longer PFS (4.6 vs 1.5 months; p>0.001) and OS (7.9 vs 3.2 months; p=0.041) compared to those not achieving clinical benefit. CONCLUSION Our findings show that single agent, weekly, intravenous carboplatin may have a role in the treatment patients with recurrent malignant glioma

Docetaxel and cisplatin in metastatic urothelial cancer: a phase II study.

1998 ◽  
Vol 16 (10) ◽  
pp. 3392-3397 ◽  
Author(s):  
L Sengeløv ◽  
C Kamby ◽  
B Lund ◽  
S A Engelholm
Keyword(s):  
Peripheral Neuropathy ◽  
Phase Ii ◽  
Urothelial Cancer ◽  
Phase Ii Study ◽  
Performance Status ◽  
Single Agent ◽  
Complete Response ◽  
World Health ◽  
Eligibility Criteria ◽  
Metastatic Urothelial Cancer

PURPOSE Docetaxel and cisplatin has documented single-agent activity and different toxicity profiles in patients with metastatic urothelial cancer. We performed a phase II study in which docetaxel was combined with cisplatin to evaluate response rate, toxicity, and survival. PATIENTS AND METHODS Eligibility criteria included performance status (World Health Organization [WHO]) less than 3; normal bone marrow, liver, and renal function; and no concurrent malignancy or symptomatic peripheral neuropathy. Docetaxel (Taxotere; Rhône-Poulenc Rorer, Paris, France) 75 mg/m2 was combined with cisplatin 75 mg/m2 every third week. Patients received premedication with prednisolone and clemastine. RESULTS A total of 25 patients were assessable for response and toxicity. Median age was 64 years; five patients had locoregional disease only and 20 had metastatic disease. Response was achieved in 15 patients (60%; 95% confidence interval [CI], 39% to 79%), including seven patients (26%) who achieved a complete response. Overall median survival time was 13.6 months (range, 1.5 to 26.4+). The most frequent toxicity was nausea and vomiting (80% of patients). Neutropenia grade 3 or 4 was observed in 56% of patients, but only one had febrile neutropenia. Mucositis and diarrhea were encountered in 13% of cycles, mostly grade 1 or 2. Peripheral neuropathy and skin changes grade 1 and 2 were observed in 76% and 36%, respectively. Fluid retention and hypersensitivity reactions were infrequent and mild. CONCLUSION The combination of docetaxel and cisplatin is effective and feasible in patients with metastatic urothelial cancer with a manageable safety profile.

scholarly journals Phase II Study of Single-agent Bevacizumab in Japanese Patients with Recurrent Malignant Glioma

2012 ◽  
Vol 42 (10) ◽  
pp. 887-895 ◽  
Author(s):  
M. Nagane ◽  
R. Nishikawa ◽  
Y. Narita ◽  
H. Kobayashi ◽  
S. Takano ◽  
...  
Keyword(s):  
Malignant Glioma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Single Agent ◽  
Japanese Patients ◽  
Recurrent Malignant Glioma

Phase II study of erlotinib given daily for patients with metastatic melanoma (MM)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 18002-18002 ◽  
Author(s):  
K. Wyman ◽  
M. Kelley ◽  
I. Puzanov ◽  
K. Sanders ◽  
F. Hubbard ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Phase Ii ◽  
Metastatic Disease ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Performance Status ◽  
Single Agent ◽  
Eligibility Criteria ◽  
Prior Therapy ◽  
Grade Iii

18002 Background: Erlotinib is a small molecule tyrosine kinase inhibitor (TKI) that targets epidermal growth factor receptor (EGFr). The EGFr is a potential therapeutic target because it is expressed by a number of malignancies, including melanocytic lesions, and in some plays an important role in the biology of the cancer. Our aim was to conduct a phase II study evaluating erlotinib in patients (pts) with measurable metastatic melanoma. Methods: Eligibility criteria included measurable disease, ECOG PS = 0–1, and adequate organ function. Pts were eligible if they received up to one prior therapy for metastatic disease. Pts received a daily dose of erlotinib 150 mg. The primary outcomes were overall response rate and response duration. The study had a two-stage design with closure at 14 pts if there were no objective RECIST responses. Secondary outcomes included overall safety and tolerability of erlotinib. Results: Between August 2003 and August 2004, a total of 14 pts with MM were accrued. The majority of pts were male 12:2 = M, median age = 57.5 yrs (range 38 to 80 yrs). Stage of disease included M1a (n = 7), M1b (n = 5), M1c (n = 2) and performance status was equally divided between 0 and 1 (7 pts each). Seven pts (50%) had prior adjuvant therapy and six pts (43%) had at least one prior therapy for metastatic disease. Four pts (29%) had no prior therapy. No objective responses were observed. Four pts (29%) had stable disease at their initial 8-week evaluation of which only 2 had SD>6 months (228 and 365 days). One pt with SD withdrew from the study on day 68 for grade II toxicities. There were no Grade III/IV hematological or biochemical toxicities. Grade III toxicities were diarrhea and anorexia, each in a single patient. Most pts (n = 12) experienced at least a grade I dermatological toxicity manifested as an acneiform rash and/or pruritis. The median progression free survival (PFS) of all 14 pts was approximately 60 days with a range of 35 to 365 days. The median PFS of those with SD was 192.5 days. Conclusions: Erlotinib given daily at 150 mg is well tolerated in pts with MM. However, it has minimal to no single agent activity. Any further investigation of this drug should be pursued in combination with other agents only if a strong scientific/clinical rationale exists. No significant financial relationships to disclose.

scholarly journals Phase II Study of Aflibercept in Recurrent Malignant Glioma: A North American Brain Tumor Consortium Study

2011 ◽  
Vol 29 (19) ◽  
pp. 2689-2695 ◽  
Author(s):  
John F. de Groot ◽  
Kathleen R. Lamborn ◽  
Susan M. Chang ◽  
Mark R. Gilbert ◽  
Timothy F. Cloughesy ◽  
...  
Keyword(s):  
Growth Factor ◽  
Malignant Glioma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Single Agent ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
Anaplastic Glioma ◽  
Recurrent Malignant Glioma ◽  
Free Survival

Purpose Antivascular endothelial growth factor (anti-VEGF) therapy is a promising treatment approach for patients with recurrent glioblastoma. This single-arm phase II study evaluated the efficacy of aflibercept (VEGF Trap), a recombinantly produced fusion protein that scavenges both VEGF and placental growth factor in patients with recurrent malignant glioma. Patients and Methods Forty-two patients with glioblastoma and 16 patients with anaplastic glioma who had received concurrent radiation and temozolomide and adjuvant temozolomide were enrolled at first relapse. Aflibercept 4 mg/kg was administered intravenously on day 1 of every 2-week cycle. Results The 6-month progression-free survival rate was 7.7% for the glioblastoma cohort and 25% for patients with anaplastic glioma. Overall radiographic response rate was 24% (18% for glioblastoma and 44% for anaplastic glioma). The median progression-free survival was 24 weeks for patients with anaplastic glioma (95% CI, 5 to 31 weeks) and 12 weeks for patients with glioblastoma (95% CI, 8 to 16 weeks). A total of 14 patients (25%) were removed from the study for toxicity, on average less than 2 months from treatment initiation. The main treatment-related National Cancer Institute Common Terminology Criteria grades 3 and 4 adverse events (38 total) included fatigue, hypertension, and lymphopenia. Two grade 4 CNS ischemias and one grade 4 systemic hemorrhage were reported. Aflibercept rapidly decreases permeability on dynamic contrast enhanced magnetic resonance imaging, and molecular analysis of baseline tumor tissue identified tumor-associated markers of response and resistance. Conclusion Aflibercept monotherapy has moderate toxicity and minimal evidence of single-agent activity in unselected patients with recurrent malignant glioma.

scholarly journals Phase II Study to Evaluate the Efficacy and Safety of Rilotumumab and Bevacizumab in Subjects with Recurrent Malignant Glioma

2018 ◽  
Vol 23 (8) ◽  
pp. 889 ◽  
Author(s):  
Mary Lou Affronti ◽  
Jennifer Gamboa Jackman ◽  
Frances McSherry ◽  
James E. Herndon ◽  
Elwood C. Massey ◽  
...  
Keyword(s):  
Malignant Glioma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Efficacy And Safety ◽  
Recurrent Malignant Glioma

scholarly journals Metronomic chemotherapy with daily, oral etoposide plus bevacizumab for recurrent malignant glioma: a phase II study

2009 ◽  
Vol 101 (12) ◽  
pp. 1986-1994 ◽  
Author(s):  
D A Reardon ◽  
A Desjardins ◽  
J J Vredenburgh ◽  
S Gururangan ◽  
J H Sampson ◽  
...  
Keyword(s):  
Malignant Glioma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Metronomic Chemotherapy ◽  
Oral Etoposide ◽  
Recurrent Malignant Glioma

A Multicentre Phase II Study of the Aminopeptidase Inhibitor, CHR- 2797, in the Treatment of Elderly and/or Previously Treated patients with Acute Myeloid Leukemia.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 961-961 ◽  
Author(s):  
B. Lowenberg ◽  
F. Davies ◽  
C. Müller-Tidow ◽  
Ulrich Dührsen ◽  
A. Burnett ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Single Agent ◽  
Clinical Activity ◽  
Open Label ◽  
Elderly Aml ◽  
Previously Treated Patients ◽  
Previously Treated

Abstract Tosedostat (TSD, CHR-2797) is an aminopeptidase inhibitor that selectively depletes amino acid pools in malignant cells, resulting in anti-proliferative, pro-apoptotic and antiangiogenic effects. In a phase I study, treatment with TSD resulted in complete remission in a number of refractory AML patients. The primary objective of this phase II study was to determine whether TSD was a sufficiently effective therapy to warrant pivotal studies. Methods. This was an open label, single agent, phase II study to assess clinical activity of TSD in elderly and/or previously treated patients with AML/MDS. Patients were treated with once daily oral doses of the maximum acceptable dose (130 mg) of TSD for up to 84 days. Further treatment was allowed if, in the opinion of the investigator, this was considered to be beneficial. Clinical responses were assessed by monthly bone marrow aspirates and weekly hematological assessments. Results. Of the 41 TSD-treated patients with AML (n=38) or MDS (n=3), who were enrolled between March and October 2007, 27 were male, 14 female, with a mean age of 67 years (range 34–82). The median performance status (ECOG) at baseline was 1 (range 0–2). Twelve (31.6%) AML patients and 2 (66.7%) MDS patients were chemotherapy naïve, and 9 (23.7%) AML patients had either secondary disease or adverse cytogenetics. For 16 (39%) patients, treatment with TSD was a second or later salvage attempt. Thirty two patients (30 AML, 2 MDS-RAEB1 and 2) received ≥28 days treatment, and 21 (51.2%) patients completed the formal 84-day study period (19 AML, 2 MDS). Nine (22%) of the patients (7 AML, 2 MDS) continued treatment with TSD after 84 days, and 6 (15%) patients were on TSD in total for more than 6 months (4 AML, 2 MDS). Ten (26.3%) of the AML patients responded to treatment; amongst these, 2 patients received TSD as 2nd/3rd salvage therapy, and a further 2 patients did not show a complete response (CR) after 2 previous induction courses of chemotherapy. Three AML patients achieved a CR (< 5% blasts in bone marrow), of whom 2 were in durable remission (232 days, continuing*; 171 days), and 7 had a partial response (PR, 5–15% blasts) lasting approximately 1–3 months. Two (66.7%) of the MDS patients also responded to treatment with TSD; these patients maintained stable disease for more than 6 months. All responders (CR, PR and SD) were >60 years at the time of the first dose. Median overall survival in AML patients was 130 days (range 8 – 478 days*). The most frequently reported adverse events were: fatigue (61%), thrombocytopenia (49%), pyrexia (39%), peripheral edema (39%) and diarrhea (34%); 9 (22%) patients withdrew due to drug related toxicity. TSD had no effect on hemoglobin or neutrophils. Conclusions. This study in patients with advanced AML/MDS with adverse prognosis demonstrates the anti-leukemic activity of TSD in elderly AML patients, as measured by CR and decreases in leukemic blasts. In addition, 2 relapsed high risk MDS patients achieved disease stabilization. TSD at 130mg qd is also very well tolerated over a long period of exposure (6–10 months). These results support further pivotal studies with TSD in elderly AML and MDS patients.

A combination chemotherapy of weekly paclitaxel and doxifluridine (5’-DFUR: an intermediate metabolite of capecitabine) in patients with unresectable or recurrent gastric cancer in an outpatient setting. Final results of a multicenter phase II trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15050-15050
Author(s):  
S. Yoshino ◽  
T. Nishimura ◽  
S. Hazama ◽  
M. Oka ◽  
H. Ozasa ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Adverse Events ◽  
Phase Ii ◽  
Response Rate ◽  
Performance Status ◽  
Single Agent ◽  
Outpatient Setting ◽  
Eligibility Criteria ◽  
Line Therapy ◽  
Recurrent Gastric Cancer

15050 Background: Paclitaxel (PTX) and 5’-DFUR have single-agent activity in gastric cancer and have distinct mechanisms of action and no overlap of key toxicities. Synergistic interaction between PTX and 5’-DFUR is mediated by taxane-induced up-regulation of thymidine phosphorylase, which converts 5’-DFUR to 5-FU. We conducted a combination phase II study of PTX and 5’-DFUR in patients with unresectable or recurrent gastric cancer to evaluate the efficacy and safety in an outpatient. Methods: Eligibility criteria included patients with histologically proven unresectable or recurrent gastric cancer who had measurable lesions fitting RECIST, up to one prior chemotherapy, a performance status of 0–2 and adequate organ function. According to our results of phase I study (Proc ASCO 2004, Abstr. 4228), the treatment included PTX 70 mg/m2 i.v. on days 1, 8, and 15 every 4 weeks and 5’-DFUR 600 mg/body p.o. everyday until there was disease progression or the appearance of unacceptable toxicity. Primary endpoint was: RR; and secondary endpoints were OS, PFS, TTF and onset rate of adverse events. Results: Between June 2004 and July 2006, 42 patients were enrolled in this study: including 34 men; 8 women; median age of 70 years (range, 44–85 years); and PS levels were, zero with 27, one with 13 and two with 2 patients. In 42 eligible patients, clinical usefulness was evaluated resulting in response rate of 40.5% (CR, 1; PR, 16; SD, 17; PD, 6; and NE, 2 patients). The first-line therapy involved 28 patients in whom the response rate was 50.0%. The second-line therapy involved 13 patients (all TS-1 failure) in whom the response rate was 23.1%. OS was 371 days, PFS was 170 days and TTF was 147 days. All patients were treated in outpatient. Severe adverse events were found in 2 patients to discontinue the present treatment, though other adverse events were relatively mild without death due to the present therapy. Commonly observed grade 3/4 adverse events were neutropenia (26.2%), appetite loss (4.8%), neuropathy (4.8%), and fatigue (4.8%). Conclusions: The outpatient combination of a weekly PTX and 5’-DFUR chemotherapy is active and well tolerated. No significant financial relationships to disclose.

Phase II study of bevacizumab and etoposide in patients with recurrent malignant glioma

2008 ◽  
Vol 26 (15_suppl) ◽  
pp. 2022-2022 ◽  
Author(s):  
J. N. Rich ◽  
A. Desjardins ◽  
S. Sathornsumetee ◽  
J. J. Vredenburgh ◽  
J. A. Quinn ◽  
...  
Keyword(s):  
Malignant Glioma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Recurrent Malignant Glioma

Phase I/II study of erlotinib and temsirolimus for patients with recurrent malignant gliomas (MG) (NABTC 04–02)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 2004-2004
Author(s):  
S. M. Chang ◽  
J. Kuhn ◽  
K. Lamborn ◽  
T. Cloughesy ◽  
I. Robins ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Single Agent ◽  
Malignant Gliomas ◽  
Mtor Inhibitors ◽  
Pharmacokinetic Data ◽  
Eligibility Criteria ◽  
Egfr Amplification ◽  
The North ◽  
Anaplastic Gliomas

2004 Background: Glioblastomas (GBM) frequently have EGFR amplification/mutations and inactivation of PTEN. Although single agent EGFR and mTOR inhibitors have limited activity, combinations of these agents may be more effective. Methods: The North American Brain Tumor Consortium conducted a phase I/II study of the EGFR inhibitor erlotinib in combination with the mTOR inhibitor temsirolimus in recurrent MG. Eligibility criteria were histologically proven GBM and anaplastic gliomas (AG), radiologic progression, >18 years old, KPS >60, adequate bone marrow and organ function. There was no limit on the number of prior relapses for phase I and no more than two prior relapses for phase II. Patients must not be receiving enzyme-inducing antiepileptic drugs. The dose of erlotinib was 150 mg/d in phase I and titrated up to maximum of 200mg/d in phase II depending on tolerability. Patients initially received temsirolimus 50 mg i.v. once weekly and the dose adjusted based on toxicities. Escalation was performed in groups of three. MTD was defined as the dose with 1/6 or fewer patients with dose-limiting toxicities (DLTs). Primary endpoint for the phase II component was PFS6. Results: In phase I, 22 patients were enrolled (15 GBM; 7 AG). Median age was 54 years (26–74); median KPS 90 (70–100); median prior relapses 1 (0–3). The MTD was determined to be 150 mg of erlotinib daily combined with 15 mg of temsirolimus weekly. DLTs were rash, mucositis, and liver function abnormalities. Pharmacokinetic data were similar to that for single agent erlotinib and temsirolimus; there was no interaction between the two drugs. AUC accumulation ratios between cycle 1 and 2 for erlotinib and OSI-420 were 3.6 and 4.6, respectively. In phase II, there were 56 patients (including 12 phase I patients treated at the MTD): 40 GBM; 16 AG, median age 47 years (20–72); median KPS 90 (range 60–100), median prior relapses 1 (range 1–3). Six patients discontinued therapy as a result of toxicities. For GBM patients, there was no PR, 30% SD, and PFS6 was 12.5%. For AG patients there was 12.5% PR, 12.5% SD, and PFS6 was 6.25%. Conclusions: The combination of erlotinib and temsirolimus was associated with a higher than expected incidence of toxicities and had minimal activity in recurrent MG. [Table: see text]

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