Phase Ib/II Trial of NC-6004 (Nanoparticle Cisplatin) Plus Gemcitabine in Patients with Advanced Solid Tumors

Publication Date:
2018-01-04
Publisher:
The American Association for Cancer Research (AACR)
Print ISSN:
1078-0432
Electronic ISSN:
1557-3265
Topics:
Medicine
Published by:
http://www.aacr.org/
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autor Subbiah, V., Grilley-Olson, J. E., Combest, A. J., Sharma, N., Tran, R. H., Bobe, I., Osada, A., Takahashi, K., Balkissoon, J., Camp, A., Masada, A., Reitsma, D. J., Bazhenova, L. A.
beschreibung Purpose: NC-6004, a novel cisplatin nanoparticle developed using micellar technology exhibits sustained release of cisplatin and selective distribution to tumors. Preclinical data demonstrated a favorable tolerability profile and preserved or improved antitumor activity compared with cisplatin across animal models. We evaluated the safety and tolerability of NC-6004 and gemcitabine using a Bayesian continual reassessment model (N-CRM) to determine the optimal dose. Experimental Design: Patients with advanced solid tumors received NC-6004 at 60 to 180 mg/m 2 on day 1 and gemcitabine at 1,250 mg/m 2 on days 1 and 8 every 3 weeks. Dose escalation of NC-6004 began with a single patient run-in until a dose-limiting toxicity occurred at 180 mg/m 2 . Cohorts of four patients were enrolled at doses predicted by the N-CRM. The maximum tolerated dose (MTD) was defined as having the greatest probability of target toxicity 〈25%. Quality of life was assessed using EORTC-QLQ-C30. Results: Among 22 patients, the most common grade III/IV hematologic adverse events were leukopenia (68%) and thrombocytopenia (59%). Of 20 pretreated patients evaluable for response, half were previously exposed to a platinum agent. The MTD was 135 mg/m 2 . Nine patients were treated at the MTD with median treatment duration of 15 weeks (range, 3–50). Tumor shrinkage occurred in 11 (55%), partial responses in 3 (15%), and stable disease in 14 (70%). Most patients reported stable or improved EORTC QLQ-C30 scores. Conclusions: Greater cisplatin equivalent doses were achieved with no clinically significant neuro-, oto-, or nephrotoxicity. These data demonstrate tolerability and promising activity of NC-6004 in combination with gemcitabine. Clin Cancer Res; 24(1); 43–51. ©2017 AACR .
citation_standardnr 6128573
datenlieferant ipn_articles
feed_id 9363
feed_publisher The American Association for Cancer Research (AACR)
feed_publisher_url http://www.aacr.org/
insertion_date 2018-01-04
journaleissn 1557-3265
journalissn 1078-0432
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher The American Association for Cancer Research (AACR)
quelle Clinical Cancer Research
relation http://clincancerres.aacrjournals.org/cgi/content/short/24/1/43?rss=1
search_space articles
shingle_author_1 Subbiah, V., Grilley-Olson, J. E., Combest, A. J., Sharma, N., Tran, R. H., Bobe, I., Osada, A., Takahashi, K., Balkissoon, J., Camp, A., Masada, A., Reitsma, D. J., Bazhenova, L. A.
shingle_author_2 Subbiah, V., Grilley-Olson, J. E., Combest, A. J., Sharma, N., Tran, R. H., Bobe, I., Osada, A., Takahashi, K., Balkissoon, J., Camp, A., Masada, A., Reitsma, D. J., Bazhenova, L. A.
shingle_author_3 Subbiah, V., Grilley-Olson, J. E., Combest, A. J., Sharma, N., Tran, R. H., Bobe, I., Osada, A., Takahashi, K., Balkissoon, J., Camp, A., Masada, A., Reitsma, D. J., Bazhenova, L. A.
shingle_author_4 Subbiah, V., Grilley-Olson, J. E., Combest, A. J., Sharma, N., Tran, R. H., Bobe, I., Osada, A., Takahashi, K., Balkissoon, J., Camp, A., Masada, A., Reitsma, D. J., Bazhenova, L. A.
shingle_catch_all_1 Phase Ib/II Trial of NC-6004 (Nanoparticle Cisplatin) Plus Gemcitabine in Patients with Advanced Solid Tumors
Purpose: NC-6004, a novel cisplatin nanoparticle developed using micellar technology exhibits sustained release of cisplatin and selective distribution to tumors. Preclinical data demonstrated a favorable tolerability profile and preserved or improved antitumor activity compared with cisplatin across animal models. We evaluated the safety and tolerability of NC-6004 and gemcitabine using a Bayesian continual reassessment model (N-CRM) to determine the optimal dose. Experimental Design: Patients with advanced solid tumors received NC-6004 at 60 to 180 mg/m 2 on day 1 and gemcitabine at 1,250 mg/m 2 on days 1 and 8 every 3 weeks. Dose escalation of NC-6004 began with a single patient run-in until a dose-limiting toxicity occurred at 180 mg/m 2 . Cohorts of four patients were enrolled at doses predicted by the N-CRM. The maximum tolerated dose (MTD) was defined as having the greatest probability of target toxicity <25%. Quality of life was assessed using EORTC-QLQ-C30. Results: Among 22 patients, the most common grade III/IV hematologic adverse events were leukopenia (68%) and thrombocytopenia (59%). Of 20 pretreated patients evaluable for response, half were previously exposed to a platinum agent. The MTD was 135 mg/m 2 . Nine patients were treated at the MTD with median treatment duration of 15 weeks (range, 3–50). Tumor shrinkage occurred in 11 (55%), partial responses in 3 (15%), and stable disease in 14 (70%). Most patients reported stable or improved EORTC QLQ-C30 scores. Conclusions: Greater cisplatin equivalent doses were achieved with no clinically significant neuro-, oto-, or nephrotoxicity. These data demonstrate tolerability and promising activity of NC-6004 in combination with gemcitabine. Clin Cancer Res; 24(1); 43–51. ©2017 AACR .
Subbiah, V., Grilley-Olson, J. E., Combest, A. J., Sharma, N., Tran, R. H., Bobe, I., Osada, A., Takahashi, K., Balkissoon, J., Camp, A., Masada, A., Reitsma, D. J., Bazhenova, L. A.
The American Association for Cancer Research (AACR)
1078-0432
10780432
1557-3265
15573265
shingle_catch_all_2 Phase Ib/II Trial of NC-6004 (Nanoparticle Cisplatin) Plus Gemcitabine in Patients with Advanced Solid Tumors
Purpose: NC-6004, a novel cisplatin nanoparticle developed using micellar technology exhibits sustained release of cisplatin and selective distribution to tumors. Preclinical data demonstrated a favorable tolerability profile and preserved or improved antitumor activity compared with cisplatin across animal models. We evaluated the safety and tolerability of NC-6004 and gemcitabine using a Bayesian continual reassessment model (N-CRM) to determine the optimal dose. Experimental Design: Patients with advanced solid tumors received NC-6004 at 60 to 180 mg/m 2 on day 1 and gemcitabine at 1,250 mg/m 2 on days 1 and 8 every 3 weeks. Dose escalation of NC-6004 began with a single patient run-in until a dose-limiting toxicity occurred at 180 mg/m 2 . Cohorts of four patients were enrolled at doses predicted by the N-CRM. The maximum tolerated dose (MTD) was defined as having the greatest probability of target toxicity <25%. Quality of life was assessed using EORTC-QLQ-C30. Results: Among 22 patients, the most common grade III/IV hematologic adverse events were leukopenia (68%) and thrombocytopenia (59%). Of 20 pretreated patients evaluable for response, half were previously exposed to a platinum agent. The MTD was 135 mg/m 2 . Nine patients were treated at the MTD with median treatment duration of 15 weeks (range, 3–50). Tumor shrinkage occurred in 11 (55%), partial responses in 3 (15%), and stable disease in 14 (70%). Most patients reported stable or improved EORTC QLQ-C30 scores. Conclusions: Greater cisplatin equivalent doses were achieved with no clinically significant neuro-, oto-, or nephrotoxicity. These data demonstrate tolerability and promising activity of NC-6004 in combination with gemcitabine. Clin Cancer Res; 24(1); 43–51. ©2017 AACR .
Subbiah, V., Grilley-Olson, J. E., Combest, A. J., Sharma, N., Tran, R. H., Bobe, I., Osada, A., Takahashi, K., Balkissoon, J., Camp, A., Masada, A., Reitsma, D. J., Bazhenova, L. A.
The American Association for Cancer Research (AACR)
1078-0432
10780432
1557-3265
15573265
shingle_catch_all_3 Phase Ib/II Trial of NC-6004 (Nanoparticle Cisplatin) Plus Gemcitabine in Patients with Advanced Solid Tumors
Purpose: NC-6004, a novel cisplatin nanoparticle developed using micellar technology exhibits sustained release of cisplatin and selective distribution to tumors. Preclinical data demonstrated a favorable tolerability profile and preserved or improved antitumor activity compared with cisplatin across animal models. We evaluated the safety and tolerability of NC-6004 and gemcitabine using a Bayesian continual reassessment model (N-CRM) to determine the optimal dose. Experimental Design: Patients with advanced solid tumors received NC-6004 at 60 to 180 mg/m 2 on day 1 and gemcitabine at 1,250 mg/m 2 on days 1 and 8 every 3 weeks. Dose escalation of NC-6004 began with a single patient run-in until a dose-limiting toxicity occurred at 180 mg/m 2 . Cohorts of four patients were enrolled at doses predicted by the N-CRM. The maximum tolerated dose (MTD) was defined as having the greatest probability of target toxicity <25%. Quality of life was assessed using EORTC-QLQ-C30. Results: Among 22 patients, the most common grade III/IV hematologic adverse events were leukopenia (68%) and thrombocytopenia (59%). Of 20 pretreated patients evaluable for response, half were previously exposed to a platinum agent. The MTD was 135 mg/m 2 . Nine patients were treated at the MTD with median treatment duration of 15 weeks (range, 3–50). Tumor shrinkage occurred in 11 (55%), partial responses in 3 (15%), and stable disease in 14 (70%). Most patients reported stable or improved EORTC QLQ-C30 scores. Conclusions: Greater cisplatin equivalent doses were achieved with no clinically significant neuro-, oto-, or nephrotoxicity. These data demonstrate tolerability and promising activity of NC-6004 in combination with gemcitabine. Clin Cancer Res; 24(1); 43–51. ©2017 AACR .
Subbiah, V., Grilley-Olson, J. E., Combest, A. J., Sharma, N., Tran, R. H., Bobe, I., Osada, A., Takahashi, K., Balkissoon, J., Camp, A., Masada, A., Reitsma, D. J., Bazhenova, L. A.
The American Association for Cancer Research (AACR)
1078-0432
10780432
1557-3265
15573265
shingle_catch_all_4 Phase Ib/II Trial of NC-6004 (Nanoparticle Cisplatin) Plus Gemcitabine in Patients with Advanced Solid Tumors
Purpose: NC-6004, a novel cisplatin nanoparticle developed using micellar technology exhibits sustained release of cisplatin and selective distribution to tumors. Preclinical data demonstrated a favorable tolerability profile and preserved or improved antitumor activity compared with cisplatin across animal models. We evaluated the safety and tolerability of NC-6004 and gemcitabine using a Bayesian continual reassessment model (N-CRM) to determine the optimal dose. Experimental Design: Patients with advanced solid tumors received NC-6004 at 60 to 180 mg/m 2 on day 1 and gemcitabine at 1,250 mg/m 2 on days 1 and 8 every 3 weeks. Dose escalation of NC-6004 began with a single patient run-in until a dose-limiting toxicity occurred at 180 mg/m 2 . Cohorts of four patients were enrolled at doses predicted by the N-CRM. The maximum tolerated dose (MTD) was defined as having the greatest probability of target toxicity <25%. Quality of life was assessed using EORTC-QLQ-C30. Results: Among 22 patients, the most common grade III/IV hematologic adverse events were leukopenia (68%) and thrombocytopenia (59%). Of 20 pretreated patients evaluable for response, half were previously exposed to a platinum agent. The MTD was 135 mg/m 2 . Nine patients were treated at the MTD with median treatment duration of 15 weeks (range, 3–50). Tumor shrinkage occurred in 11 (55%), partial responses in 3 (15%), and stable disease in 14 (70%). Most patients reported stable or improved EORTC QLQ-C30 scores. Conclusions: Greater cisplatin equivalent doses were achieved with no clinically significant neuro-, oto-, or nephrotoxicity. These data demonstrate tolerability and promising activity of NC-6004 in combination with gemcitabine. Clin Cancer Res; 24(1); 43–51. ©2017 AACR .
Subbiah, V., Grilley-Olson, J. E., Combest, A. J., Sharma, N., Tran, R. H., Bobe, I., Osada, A., Takahashi, K., Balkissoon, J., Camp, A., Masada, A., Reitsma, D. J., Bazhenova, L. A.
The American Association for Cancer Research (AACR)
1078-0432
10780432
1557-3265
15573265
shingle_title_1 Phase Ib/II Trial of NC-6004 (Nanoparticle Cisplatin) Plus Gemcitabine in Patients with Advanced Solid Tumors
shingle_title_2 Phase Ib/II Trial of NC-6004 (Nanoparticle Cisplatin) Plus Gemcitabine in Patients with Advanced Solid Tumors
shingle_title_3 Phase Ib/II Trial of NC-6004 (Nanoparticle Cisplatin) Plus Gemcitabine in Patients with Advanced Solid Tumors
shingle_title_4 Phase Ib/II Trial of NC-6004 (Nanoparticle Cisplatin) Plus Gemcitabine in Patients with Advanced Solid Tumors
timestamp 2025-06-30T23:31:42.894Z
titel Phase Ib/II Trial of NC-6004 (Nanoparticle Cisplatin) Plus Gemcitabine in Patients with Advanced Solid Tumors
titel_suche Phase Ib/II Trial of NC-6004 (Nanoparticle Cisplatin) Plus Gemcitabine in Patients with Advanced Solid Tumors
topic WW-YZ
uid ipn_articles_6128573