Phase II trial of carfilzomib and irinotecan in relapsed small cell lung cancer (NCT01941316).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 8513-8513 ◽  
Author(s):  
Susanne M. Arnold ◽  
Kari Chansky ◽  
Maria Quintos Baggstrom ◽  
Michael A. Thompson ◽  
Rachel E. Sanborn ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Phase Ii ◽  
Cell Lung Cancer ◽  
Progression Free Survival ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Platinum Sensitive ◽  
Platinum Refractory

8513 Background: Relapsed small cell lung cancer (SCLC) is incurable with limited therapeutic options. This phase II study evaluated efficacy and tolerability of carfilzomib + irinotecan in SCLC pts who progressed after prior platinum-based therapy, based on expected synergy of proteosome inhibitor carfilzomib and topisomerase 1 inhibitor irinotecan. Methods: SCLC pts who progressed after one platinum-containing regimen (no maintenance therapy allowed) for recurrent/metastatic disease were eligible. Pts were stratified by response to platinum-based therapy: sensitive (progressive disease (PD) > 90 days after chemo) versus refractory (PD 30 to 90 days after chemo). Pts were treated with up to 6 cycles of carfilzomib (20/36 mg.m2 D1, 2, 8, 9, 15, 16 q28D) and irinotecan (125 mg/m2 D1, 8, 15 q28D), imaging was performed every 2 cycles. The primary efficacy endpoint was 6-month overall survival (OS). Results: 62 pts enrolled and were evaluable for efficacy and adverse events. The 6-month OS was 59% in the platinum sensitive stratum and 54% in the platinum refractory stratum. Overall response rate: sensitive stratum 21.6% (1.6% CR + 16.4% PR) and refractory stratum 12.5% (all PR). Disease control (SD+PR+CR) was 68% in platinum sensitive and 56% in refractory patients. Progression free survival and OS were 3.6 months (95% CI 2.6 - 4.6) and 6.9 months (95% CI 4.3 - 12.3) in the sensitive stratum, and 3.3 months (95% CI 1.8 – 3.9) and 6.8 months (95% CI 4.1-11) in the refractory stratum. Twenty-nine pts (47%) experienced at least one grade 3 AE and 8 subjects had grade 4 toxicities: decreased neutrophils, leukocytes, and lymphocytes, diarrhea, vomiting, sepsis, hypokalemia, hypocalcemia, and dehydration. There were three treatment related deaths: myocardial infarction (possible), lung infection (possible), sepsis (probable). Conclusions: In previously treated pts with relapsed SCLC, irinotecan and carfilzomib was effective in platinum-sensitive and, notably, platinum-refractory pts with similar toxicity profile. This combination is a viable option in relapsed SCLC, can be considered following progression on immunotherapy (IO) or in subjects who cannot receive IO, and should be further explored in a randomized phase III trial. Clinical trial information: NCT01941316.

Phase III Study of Erlotinib in Combination With Cisplatin and Gemcitabine in Advanced Non–Small-Cell Lung Cancer: The Tarceva Lung Cancer Investigation Trial

2007 ◽  
Vol 25 (12) ◽  
pp. 1545-1552 ◽  
Author(s):  
Ulrich Gatzemeier ◽  
Anna Pluzanska ◽  
Aleksandra Szczesna ◽  
Eckhard Kaukel ◽  
Jaromir Roubec ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Single Agent ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Double Blind

Purpose Erlotinib is a potent inhibitor of the epidermal growth factor receptor tyrosine kinase, with single-agent antitumor activity. Preclinically, erlotinib enhanced the cytotoxicity of chemotherapy. This phase III, randomized, double-blind, placebo-controlled, multicenter trial evaluated the efficacy and safety of erlotinib in combination with cisplatin and gemcitabine as first-line treatment for advanced non–small-cell lung cancer (NSCLC). Patients and Methods Patients received erlotinib (150 mg/d) or placebo, combined with up to six 21-day cycles of chemotherapy (gemcitabine 1,250 mg/m2 on days 1 and 8 and cisplatin 80 mg/m2 on day 1). The primary end point was overall survival (OS). Secondary end points included time to disease progression (TTP), response rate (RR), duration of response, and quality of life (QoL). Results A total of 1,172 patients were enrolled. Baseline demographic and disease characteristics were well balanced. There were no differences in OS (hazard ratio, 1.06; median, 43 v 44.1 weeks for erlotinib and placebo groups, respectively), TTP, RR, or QoL between treatment arms. In a small group of patients who had never smoked, OS and progression-free survival were increased in the erlotinib group; no other subgroups were found more likely to benefit. Erlotinib with chemotherapy was generally well tolerated; incidence of adverse events was similar between arms, except for an increase in rash and diarrhea with erlotinib (generally mild). Conclusion Erlotinib with concurrent cisplatin and gemcitabine showed no survival benefit compared with chemotherapy alone in patients with chemotherapy-naïve advanced NSCLC.

Topotecan plus ifosfamide in patients with platinum refractory advanced/metastatic non-small cell lung cancer: A phase II trial

2005 ◽  
Author(s):  
Vito Lorusso ◽  
Vittorio Gebbia ◽  
Massimiliano Spada ◽  
Michele Guida ◽  
Grazia Cassano ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Phase Ii ◽  
Cell Lung Cancer ◽  
Phase Ii Trial ◽  
Small Cell ◽  
Small Cell Lung ◽  
Platinum Refractory

Phase III Study Comparing Amrubicin Plus Cisplatin With Irinotecan Plus Cisplatin in the Treatment of Extensive-Disease Small-Cell Lung Cancer: JCOG 0509

2014 ◽  
Vol 32 (12) ◽  
pp. 1262-1268 ◽  
Author(s):  
Miyako Satouchi ◽  
Yoshikazu Kotani ◽  
Taro Shibata ◽  
Masahiko Ando ◽  
Kazuhiko Nakagawa ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Progression Free Survival ◽  
Small Cell ◽  
Phase Iii ◽  
Point Estimate ◽  
Small Cell Lung ◽  
Extensive Disease ◽  
Grade 3

Purpose This randomized phase III trial was conducted to confirm noninferiority of amrubicin plus cisplatin (AP) compared with irinotecan plus cisplatin (IP) in terms of overall survival (OS) in chemotherapy-naive patients with extensive-disease (ED) small-cell lung cancer (SCLC). Patients and Methods Chemotherapy-naive patients with ED-SCLC were randomly assigned to receive IP, composed of irinotecan 60 mg/m2 on days 1, 8, and 15 and cisplatin 60 mg/m2 on day 1 every 4 weeks, or AP, composed of amrubicin 40 mg/m2 on days 1, 2, and 3 and cisplatin 60 mg/m2 on day 1 every 3 weeks. Results A total of 284 patients were randomly assigned to IP (n = 142) and AP (n = 142) arms. The point estimate of OS hazard ratio (HR) for AP to IP in the second interim analysis exceeded the noninferior margin (HR, 1.31), resulting in early publication because of futility. In updated analysis, median survival time was 17.7 (IP) versus 15.0 months (AP; HR, 1.43; 95% CI, 1.10 to 1.85), median progression-free survival was 5.6 (IP) versus 5.1 months (AP; HR, 1.42; 95% CI, 1.16 to 1.73), and response rate was 72.3% (IP) versus 77.9% (AP; P = .33). Adverse events observed in IP and AP arms were grade 4 neutropenia (22.5% v 79.3%), grade 3 to 4 febrile neutropenia (10.6% v 32.1%), and grade 3 to 4 diarrhea (7.7% v 1.4%). Conclusion AP proved inferior to IP in this trial, perhaps because the efficacy of amrubicin as a salvage therapy was differentially beneficial to IP. IP remains the standard treatment for extensive-stage SCLC in Japan.

Phase II study of docetaxel for advanced or metastatic platinum-refractory non-small-cell lung cancer.

1995 ◽  
Vol 13 (3) ◽  
pp. 645-651 ◽  
Author(s):  
F V Fossella ◽  
J S Lee ◽  
D M Shin ◽  
M Calayag ◽  
M Huber ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Side Effects ◽  
Small Cell Lung Cancer ◽  
Phase Ii ◽  
Cell Lung Cancer ◽  
Phase Ii Study ◽  
Small Cell ◽  
Fluid Retention ◽  
Small Cell Lung ◽  
Platinum Refractory

PURPOSE We conducted a phase II study to determine the response to and toxicity of docetaxel (Taxotere; Rhône-Poulenc Rorer Pharmaceuticals, Inc, Collegeville, PA) in patients with advanced non-small-cell lung cancer refractory to prior platinum-containing chemotherapy (PCC) regimens. PATIENTS AND METHODS Forty-four patients with stage IIIb or IV platinum-refractory non-small-cell lung cancer were treated with 100 mg/m2 of docetaxel intravenously over 1 hour every 3 weeks. The responses of 42 of 44 patients were assessable. Most patients had a Zubrod performance status of 1; the predominant histologic type was adenocarcinoma (61%), and 91% of patients had stage IV disease. RESULTS Nine of 42 assessable patients (21%) achieved a partial response to treatment. The median response duration (from response to progression) was 17 weeks, and the projected median survival duration of all patients is 42 weeks (51 weeks for adenocarcinoma and 22 weeks for nonadenocarcinoma). Grade 3/4 neutropenia occurred in 85% of patients and was associated with fever that required intravenous antibiotics in 16% of patients (3% of cycles). Other acute side effects included easily treated hypersensitivity reactions and dermatitis. Cumulative side effects included fluid retention and neuropathy. CONCLUSION Docetaxel administered at 100 mg/m2 intravenously every 3 weeks has notable activity against platinum-refractory non-small-cell lung cancer, with a 21% major response rate. Primary side effects were neutropenia, hypersensitivity, and fluid retention.

scholarly journals Phase III study of selpercatinib vs chemotherapy +/− pembrolizumab in untreated RET positive non-small-cell lung cancer

2020 ◽  
Author(s):  
Benjamin J Solomon ◽  
Cai Cun Zhou ◽  
Alexander Drilon ◽  
Keunchil Park ◽  
Jürgen Wolf ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Trial ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Progression Free Survival ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Free Survival ◽  
Treatment Naïve

Selpercatinib, a novel, highly selective and potent, inhibitor of RET, demonstrated clinically meaningful antitumor activity with manageable toxicity in heavily pretreated and treatment-naive RET fusion-positive non-small-cell lung cancer patients in a Phase I/II clinical trial. LIBRETTO-431 (NCT04194944) is a randomized, global, multicenter, open-label, Phase III trial, evaluating selpercatinib versus carboplatin or cisplatin and pemetrexed chemotherapy with or without pembrolizumab in treatment-naive patients with locally advanced/metastatic RET fusion-positive nonsquamous non-small-cell lung cancer. The primary end point is progression-free survival by independent review. Key secondary end points include overall survival, response rate, duration of response and progression-free survival. Clinical trial registration: NCT04194944 (ClinicalTrials.gov)

Gemcitabine Plus Vinorelbine Compared With Cisplatin Plus Vinorelbine or Cisplatin Plus Gemcitabine for Advanced Non–Small-Cell Lung Cancer: A Phase III Trial of the Italian GEMVIN Investigators and the National Cancer Institute of Canada Clinical Trials Group

2003 ◽  
Vol 21 (16) ◽  
pp. 3025-3034 ◽  
Author(s):  
Cesare Gridelli ◽  
Ciro Gallo ◽  
Frances A. Shepherd ◽  
Alfonso Illiano ◽  
Francovito Piantedosi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Progression Free Survival ◽  
Small Cell ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Small Cell Lung ◽  
European Organization ◽  
Grade 3

Purpose: Platinum-containing chemotherapy regimens are the standard treatment for patients with advanced non–small-cell lung cancer (NSCLC), although toxicity is common and may significantly affect the patient’s quality of life (QoL). This trial aimed to assess whether a combination of gemcitabine and vinorelbine had benefits in terms of QoL, without influencing negatively on survival, compared with cisplatin-containing regimens. Patients and Methods: Patients with stage IIIB (effusion and supraclavicular nodes) or IV documented NSCLC who were younger than 70 years of age were randomly assigned gemcitabine plus vinorelbine (GemVin) or either gemcitabine plus cisplatin or vinorelbine plus cisplatin (cisplatin-based). European Organization for Research and Treatment of Cancer scales were used for QoL analysis. Results: Five hundred one patients were randomly assigned to treatment. The median age was 62 years. There were no significant differences in global QoL scores between the two arms after 2 months of treatment. However, worsening scores for appetite, vomiting, and alopecia were significantly more common in the cisplatin-based arm. Median survival was 38 v 32 weeks and median progression-free survival was 23 v 17 weeks in the cisplatin-based versus GemVin arms, respectively. For the GemVin arm the hazard ratio for death was 1.15 (90% confidence interval [CI], 0.96 to 1.37) and the hazard ratio for progression was 1.29 (90% CI, 1.10 to 1.52). Grade 3 or 4 myelosuppression, vomiting, alopecia, and ototoxicity were significantly more frequent with cisplatin-based treatment. Conclusion: Global QoL is not improved with GemVin, although advantages in some components of QoL were apparent. GemVin is less toxic than standard cisplatin-based chemotherapy. There is a nonsignificant slight survival advantage with cisplatin-based chemotherapy. GemVin could be offered to advanced NSCLC patients who express concern about toxicity.

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