Multicenter, Phase II Study of Cetuximab in Combination With Carboplatin in Patients With Recurrent or Metastatic Nasopharyngeal Carcinoma

2005 ◽  
Vol 23 (15) ◽  
pp. 3568-3576 ◽  
Author(s):  
Anthony T.C. Chan ◽  
Mow-Ming Hsu ◽  
Boon C. Goh ◽  
Edwin P. Hui ◽  
Tsang-Wu Liu ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Area Under The Curve ◽  
Growth Factor Receptor ◽  
Clinical Activity ◽  
Open Label ◽  
Platinum Based Chemotherapy ◽  
Metastatic Nasopharyngeal Carcinoma ◽  
Heavily Pretreated

Purpose To evaluate efficacy and toxicity of cetuximab plus carboplatin in recurrent or metastatic nasopharyngeal carcinoma (NPC) resistant to platinum treatment. Patients and Methods A multicenter, open-label, single-arm, phase II study in patients with epidermal growth factor receptor–expressing NPC who progressed on or within 12 months after termination of platinum-based chemotherapy for recurrent or metastatic disease. Cetuximab was administered at an initial dose of 400 mg/m2 followed by weekly doses of 250 mg/m2. Carboplatin area under the curve 5 was administered every 3 weeks up to a maximum of eight cycles. Results Sixty patients were enrolled (46 males, 14 females; median age, 44.5 years; range, 23 to 64 years), and all patients were included in the intent-to-treat and safety analyses. Of the 59 patients assessable for efficacy, there were seven partial responses (11.7%), 29 patients (48.3%) with stable disease, and 23 patients (38.3%) with progressive disease, giving an overall response rate of 11.7% (95% CI, 4.8% to 22.6%). The median time to progression was 81 days in all patients and was longest in the group of patients with a confirmed response (173 days). The median overall survival time was 233 days in all patients. Six patients (10%) experienced serious treatment-related adverse events. Grade 3 or 4 toxicities occurred in 31 patients (51.7%); of these patients, only 19 (31.7%) were considered to have toxicity related to cetuximab. Conclusion Cetuximab in combination with carboplatin demonstrates clinical activity and an acceptable safety profile in heavily pretreated patients with recurrent or metastatic NPC who had previously experienced treatment failure with platinum-based therapy.

A phase II, multicenter, open-label, single-arm trial of famitinib in patients with advanced recurrent and/or metastatic nasopharyngeal carcinoma (NPC) after two previous treatment regimens.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6026-6026 ◽  
Author(s):  
Yan Huang ◽  
Li Zhang ◽  
Jian-ji Pan ◽  
Guoqing Hu ◽  
Wu Gang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Nasopharyngeal Carcinoma ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Growth Factor Receptor ◽  
Previous Treatment ◽  
Open Label ◽  
Primary Object ◽  
Biomarker Analysis ◽  
Metastatic Nasopharyngeal Carcinoma

6026 Background: Famitinib is an oral, small molecular multiple tyrosine-kinase inhibitor (TKI), targeting stem cell growth factor receptor (c-Kit), platelet derived growth factor receptor (PDGFR) and vascular endothelial growth factor receptor (VEGFR). So far, few target therapies show acceptable efficiency in advanced recurrent and/or metastatic nasopharyngeal carcinoma (RM-NPC) patients. The primary object of this study is to determine the safety and efficacy of famitinib in patients with RM-NPC. Methods: This study recruited histologically diagnosed RM-NPC patients who failed more than two lines of systemic chemotherapy. Other eligible criteria included ECOG PS≤2, adequate organ function and no prior exposure to other c-Kit, PDGFR or VEGFR TKIs. The patients received famitinib orally at a dose of 25 mg once daily until the disease progression or intolerable toxicity. Results: From May 2011 to Sep 2012, 58 patients (Simon’s two-stage design, 28+30) were recruited at 8 sites in China. The clinical benefit rate (partial response or stable disease maintained≥12 weeks, tumor response was evaluated every 4 weeks) is 32.8%, including 5 PR and 16 SD patients. Median PFS was 3.2 months. The most frequently observed hematologic toxicities included thrombocytopenia, leucopenia and neutropenia; non-hematologic AEs were hypertension, proteinuria, and hand-foot syndrome. All adverse events were generally mild-to-moderate (grade 1/2) and manageable with supportive treatment; grade 3/4 incidence was relatively low. Conclusions: This phase II study shows that famitinib demonstrates substantial clinical benefits in patients with advanced RM-NPC and the drug-related adverse reactions were most predictable and tolerable, no special toxicity was reported. Biomarker analysis for responder and non-responder is still ongoing and will be present at the meeting. Clinical trial information: NCT01392235.

scholarly journals Pyrotinib in HER2-Mutant Advanced Lung Adenocarcinoma After Platinum-Based Chemotherapy: A Multicenter, Open-Label, Single-Arm, Phase II Study

2020 ◽  
Vol 38 (24) ◽  
pp. 2753-2761 ◽  
Author(s):  
Caicun Zhou ◽  
Xingya Li ◽  
Qiming Wang ◽  
Guanghui Gao ◽  
Yiping Zhang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Phase Ii ◽  
Objective Response Rate ◽  
Response Rate ◽  
Phase Ii Study ◽  
Objective Response ◽  
Unmet Need ◽  
Open Label ◽  
Platinum Based Chemotherapy ◽  
Grade 3

PURPOSE Targeted therapies against non–small-cell lung cancer (NSCLC) harboring HER2 mutations remain an unmet need. In this study, we assessed the efficacy and safety of pyrotinib in patients with HER2-mutant advanced NSCLC in a prospective, multicenter, open-label, single-arm, phase II study. PATIENTS AND METHODS Patients with stage IIIB or IV HER2-mutant lung adenocarcinoma who were previously treated with platinum-based chemotherapy were enrolled to receive pyrotinib at a dose of 400 mg/d for 21-day cycles. The primary end point was objective response rate per independent review committee (IRC). RESULTS Between October 20, 2016, and December 10, 2018, 60 patients received pyrotinib monotherapy. At baseline, 58 (96.7%) were stage IV, and 25 (41.7%) received at least 2 lines of prior chemotherapy. As of data cutoff on June 20, 2019, IRC-assessed objective response rate was 30.0% (95% CI, 18.8% to 43.2%). All subgroups of patients with different HER2 mutation types showed a favorable objective response rate. The objective response rates were similar between patients with and without brain metastases (25.0% v 31.3%). The median duration of response was 6.9 months (95% CI, 4.9 to 11.1 months). The median progression-free survival was 6.9 months (95% CI, 5.5 to 8.3 months) per IRC. The median overall survival was 14.4 months (95% CI, 12.3 to 21.3 months). Treatment-related adverse events of grade 3 or 4 occurred in 28.3% of patients, with the most common being diarrhea (20.0%; all grade 3). No treatment-related deaths were reported. CONCLUSION Pyrotinib showed promising antitumor activity and an acceptable safety profile in chemotherapy-treated patients with HER2-mutant NSCLC.

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 multicohort phase II study of durvalumab plus tremelimumab for the treatment of patients (PTS) with advanced neuroendocrine neoplasms (NENs) of gastroenteropancreatic (GEP) or lung origin (the DUNE trial-GETNE1601-).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS4146-TPS4146
Author(s):  
Ignacio Matos Garcia ◽  
Enrique Grande ◽  
Rocio Garcia-Carbonero ◽  
Carlos Lopez ◽  
Alexandre Teule ◽  
...  
Keyword(s):  
Phase Ii ◽  
Primary Endpoint ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Tumor Growth Rate ◽  
Neuroendocrine Neoplasms ◽  
Low Grade ◽  
Open Label ◽  
Platinum Based Chemotherapy ◽  
Tumor Load

TPS4146 Background: NENs include a heterogeneous group of tumors with different behavior. Despite immunomodulators such as interferon are approved for the management of grade 1-2 NENs, the low mutation tumor load and PD-1/PDL-1 expression have limited the development of immune check-point inhibitors in this setting. The rational for immunotherapy in high grade NENs is stronger compared with low grade NENs based on the results observed in small cell lung cancer. However, the combination of an antiPDL-1 and antiCTLA-4 could increase the probability of success regardless of tumor growth rate, mutational tumor load or PDL-1 expression in low grade NENs. Methods: This prospective, multi-center, open label, phase II study (EudraCT:2016-002858-20) will evaluate the efficacy and safety of durvalumab plus tremelimumab in 126 pts within four different cohorts, including well-moderately differentiated lung NENs (Cohort 1), grade 1-2 gastrointestinal NENs (Cohort 2), grade 1-2 pancreatic NENs (Cohort 3) and grade 3 GEP NENs (Cohort 4). To optimize the efficacy of immunotherapy in low grade NENs, pts included in the trial must have progressed to all standard approved therapy in each setting, including somatostatin analogues, targeted agents and chemotherapy for lung and GEP grade 1-2 NENs up to 4 prior lines. For pts included in cohort 4, progression to standard platinum-based chemotherapy is mandatory. All pts will receive durvalumab 1500 mg every 28 days for 12 months, and tremelimumab 75 mg Q4W up to 4 doses/cycles. Retreatment is allowed after disease progression in the follow-up period. The primary endpoint of the study for cohorts 1-3 is disease control rate at 9 months including the percentage of pts achieving complete response, partial response, or stable disease according to RECIST v1.1; Median overall survival will be the primary endpoint for cohort 4. Primary endpoints will be assessed by investigators and confirmed by central radiological review. Secondary endpoints include median progression-free survival, safety and tolerability and a wide panel of biomarkers in blood samples and tumor tissue. Clinical trial information: 2016-002858-20.

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