A Phase I Clinical Trial of the Poly(ADP-ribose) Polymerase Inhibitor Veliparib and Weekly Topotecan in Patients with Solid Tumors

Publication Date:
2018-02-16
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 Wahner Hendrickson, A. E., Menefee, M. E., Hartmann, L. C., Long, H. J., Northfelt, D. W., Reid, J. M., Boakye-Agyeman, F., Kayode, O., Flatten, K. S., Harrell, M. I., Swisher, E. M., Poirer, G. G., Satele, D., Allred, J., Lensing, J. L., Chen, A., Ji, J., Zang, Y., Erlichman, C., Haluska, P., Kaufmann, S. H.
beschreibung Purpose: To determine the dose limiting toxicities (DLT), maximum tolerated dose (MTD), and recommended phase II dose (RP2D) of veliparib in combination with weekly topotecan in patients with solid tumors. Correlative studies were included to assess the impact of topotecan and veliparib on poly(ADP-ribose) levels in peripheral blood mononuclear cells, serum pharmacokinetics of both agents, and potential association of germline repair gene mutations with outcome. Experimental Design: Eligible patients had metastatic nonhematologic malignancies with measurable disease. Using a 3 + 3 design, patients were treated with veliparib orally twice daily on days 1–3, 8–10, and 15–17 and topotecan intravenously on days 2, 9, and 16 every 28 days. Tumor responses were assessed by RECIST. Results: Of 58 patients enrolled, 51 were evaluable for the primary endpoint. The MTD and RP2D was veliparib 300 mg twice daily on days 1–3, 8–10, and 15–17 along with topotecan 3 mg/m 2 on days 2, 9, and 16 of a 28-day cycle. DLTs were grade 4 neutropenia lasting 〉5 days. The median number of cycles was 2 (1–26). The objective response rate was 10%, with 1 complete and 4 partial responses. Twenty-two patients (42%) had stable disease ranging from 4 to 26 cycles. Patients with germline BRCA1, BRCA2 , or RAD51D mutations remained on study longer than those without homologous recombination repair (HRR) gene mutations (median 4 vs. 2 cycles). Conclusions: Weekly topotecan in combination with veliparib has a manageable safety profile and appears to warrant further investigation. Clin Cancer Res; 24(4); 744–52. ©2017 AACR .
citation_standardnr 6166100
datenlieferant ipn_articles
feed_id 9363
feed_publisher The American Association for Cancer Research (AACR)
feed_publisher_url http://www.aacr.org/
insertion_date 2018-02-16
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/24/4/744?rss=1
search_space articles
shingle_author_1 Wahner Hendrickson, A. E., Menefee, M. E., Hartmann, L. C., Long, H. J., Northfelt, D. W., Reid, J. M., Boakye-Agyeman, F., Kayode, O., Flatten, K. S., Harrell, M. I., Swisher, E. M., Poirer, G. G., Satele, D., Allred, J., Lensing, J. L., Chen, A., Ji, J., Zang, Y., Erlichman, C., Haluska, P., Kaufmann, S. H.
shingle_author_2 Wahner Hendrickson, A. E., Menefee, M. E., Hartmann, L. C., Long, H. J., Northfelt, D. W., Reid, J. M., Boakye-Agyeman, F., Kayode, O., Flatten, K. S., Harrell, M. I., Swisher, E. M., Poirer, G. G., Satele, D., Allred, J., Lensing, J. L., Chen, A., Ji, J., Zang, Y., Erlichman, C., Haluska, P., Kaufmann, S. H.
shingle_author_3 Wahner Hendrickson, A. E., Menefee, M. E., Hartmann, L. C., Long, H. J., Northfelt, D. W., Reid, J. M., Boakye-Agyeman, F., Kayode, O., Flatten, K. S., Harrell, M. I., Swisher, E. M., Poirer, G. G., Satele, D., Allred, J., Lensing, J. L., Chen, A., Ji, J., Zang, Y., Erlichman, C., Haluska, P., Kaufmann, S. H.
shingle_author_4 Wahner Hendrickson, A. E., Menefee, M. E., Hartmann, L. C., Long, H. J., Northfelt, D. W., Reid, J. M., Boakye-Agyeman, F., Kayode, O., Flatten, K. S., Harrell, M. I., Swisher, E. M., Poirer, G. G., Satele, D., Allred, J., Lensing, J. L., Chen, A., Ji, J., Zang, Y., Erlichman, C., Haluska, P., Kaufmann, S. H.
shingle_catch_all_1 A Phase I Clinical Trial of the Poly(ADP-ribose) Polymerase Inhibitor Veliparib and Weekly Topotecan in Patients with Solid Tumors
Purpose: To determine the dose limiting toxicities (DLT), maximum tolerated dose (MTD), and recommended phase II dose (RP2D) of veliparib in combination with weekly topotecan in patients with solid tumors. Correlative studies were included to assess the impact of topotecan and veliparib on poly(ADP-ribose) levels in peripheral blood mononuclear cells, serum pharmacokinetics of both agents, and potential association of germline repair gene mutations with outcome. Experimental Design: Eligible patients had metastatic nonhematologic malignancies with measurable disease. Using a 3 + 3 design, patients were treated with veliparib orally twice daily on days 1–3, 8–10, and 15–17 and topotecan intravenously on days 2, 9, and 16 every 28 days. Tumor responses were assessed by RECIST. Results: Of 58 patients enrolled, 51 were evaluable for the primary endpoint. The MTD and RP2D was veliparib 300 mg twice daily on days 1–3, 8–10, and 15–17 along with topotecan 3 mg/m 2 on days 2, 9, and 16 of a 28-day cycle. DLTs were grade 4 neutropenia lasting >5 days. The median number of cycles was 2 (1–26). The objective response rate was 10%, with 1 complete and 4 partial responses. Twenty-two patients (42%) had stable disease ranging from 4 to 26 cycles. Patients with germline BRCA1, BRCA2 , or RAD51D mutations remained on study longer than those without homologous recombination repair (HRR) gene mutations (median 4 vs. 2 cycles). Conclusions: Weekly topotecan in combination with veliparib has a manageable safety profile and appears to warrant further investigation. Clin Cancer Res; 24(4); 744–52. ©2017 AACR .
Wahner Hendrickson, A. E., Menefee, M. E., Hartmann, L. C., Long, H. J., Northfelt, D. W., Reid, J. M., Boakye-Agyeman, F., Kayode, O., Flatten, K. S., Harrell, M. I., Swisher, E. M., Poirer, G. G., Satele, D., Allred, J., Lensing, J. L., Chen, A., Ji, J., Zang, Y., Erlichman, C., Haluska, P., Kaufmann, S. H.
The American Association for Cancer Research (AACR)
1078-0432
10780432
1557-3265
15573265
shingle_catch_all_2 A Phase I Clinical Trial of the Poly(ADP-ribose) Polymerase Inhibitor Veliparib and Weekly Topotecan in Patients with Solid Tumors
Purpose: To determine the dose limiting toxicities (DLT), maximum tolerated dose (MTD), and recommended phase II dose (RP2D) of veliparib in combination with weekly topotecan in patients with solid tumors. Correlative studies were included to assess the impact of topotecan and veliparib on poly(ADP-ribose) levels in peripheral blood mononuclear cells, serum pharmacokinetics of both agents, and potential association of germline repair gene mutations with outcome. Experimental Design: Eligible patients had metastatic nonhematologic malignancies with measurable disease. Using a 3 + 3 design, patients were treated with veliparib orally twice daily on days 1–3, 8–10, and 15–17 and topotecan intravenously on days 2, 9, and 16 every 28 days. Tumor responses were assessed by RECIST. Results: Of 58 patients enrolled, 51 were evaluable for the primary endpoint. The MTD and RP2D was veliparib 300 mg twice daily on days 1–3, 8–10, and 15–17 along with topotecan 3 mg/m 2 on days 2, 9, and 16 of a 28-day cycle. DLTs were grade 4 neutropenia lasting >5 days. The median number of cycles was 2 (1–26). The objective response rate was 10%, with 1 complete and 4 partial responses. Twenty-two patients (42%) had stable disease ranging from 4 to 26 cycles. Patients with germline BRCA1, BRCA2 , or RAD51D mutations remained on study longer than those without homologous recombination repair (HRR) gene mutations (median 4 vs. 2 cycles). Conclusions: Weekly topotecan in combination with veliparib has a manageable safety profile and appears to warrant further investigation. Clin Cancer Res; 24(4); 744–52. ©2017 AACR .
Wahner Hendrickson, A. E., Menefee, M. E., Hartmann, L. C., Long, H. J., Northfelt, D. W., Reid, J. M., Boakye-Agyeman, F., Kayode, O., Flatten, K. S., Harrell, M. I., Swisher, E. M., Poirer, G. G., Satele, D., Allred, J., Lensing, J. L., Chen, A., Ji, J., Zang, Y., Erlichman, C., Haluska, P., Kaufmann, S. H.
The American Association for Cancer Research (AACR)
1078-0432
10780432
1557-3265
15573265
shingle_catch_all_3 A Phase I Clinical Trial of the Poly(ADP-ribose) Polymerase Inhibitor Veliparib and Weekly Topotecan in Patients with Solid Tumors
Purpose: To determine the dose limiting toxicities (DLT), maximum tolerated dose (MTD), and recommended phase II dose (RP2D) of veliparib in combination with weekly topotecan in patients with solid tumors. Correlative studies were included to assess the impact of topotecan and veliparib on poly(ADP-ribose) levels in peripheral blood mononuclear cells, serum pharmacokinetics of both agents, and potential association of germline repair gene mutations with outcome. Experimental Design: Eligible patients had metastatic nonhematologic malignancies with measurable disease. Using a 3 + 3 design, patients were treated with veliparib orally twice daily on days 1–3, 8–10, and 15–17 and topotecan intravenously on days 2, 9, and 16 every 28 days. Tumor responses were assessed by RECIST. Results: Of 58 patients enrolled, 51 were evaluable for the primary endpoint. The MTD and RP2D was veliparib 300 mg twice daily on days 1–3, 8–10, and 15–17 along with topotecan 3 mg/m 2 on days 2, 9, and 16 of a 28-day cycle. DLTs were grade 4 neutropenia lasting >5 days. The median number of cycles was 2 (1–26). The objective response rate was 10%, with 1 complete and 4 partial responses. Twenty-two patients (42%) had stable disease ranging from 4 to 26 cycles. Patients with germline BRCA1, BRCA2 , or RAD51D mutations remained on study longer than those without homologous recombination repair (HRR) gene mutations (median 4 vs. 2 cycles). Conclusions: Weekly topotecan in combination with veliparib has a manageable safety profile and appears to warrant further investigation. Clin Cancer Res; 24(4); 744–52. ©2017 AACR .
Wahner Hendrickson, A. E., Menefee, M. E., Hartmann, L. C., Long, H. J., Northfelt, D. W., Reid, J. M., Boakye-Agyeman, F., Kayode, O., Flatten, K. S., Harrell, M. I., Swisher, E. M., Poirer, G. G., Satele, D., Allred, J., Lensing, J. L., Chen, A., Ji, J., Zang, Y., Erlichman, C., Haluska, P., Kaufmann, S. H.
The American Association for Cancer Research (AACR)
1078-0432
10780432
1557-3265
15573265
shingle_catch_all_4 A Phase I Clinical Trial of the Poly(ADP-ribose) Polymerase Inhibitor Veliparib and Weekly Topotecan in Patients with Solid Tumors
Purpose: To determine the dose limiting toxicities (DLT), maximum tolerated dose (MTD), and recommended phase II dose (RP2D) of veliparib in combination with weekly topotecan in patients with solid tumors. Correlative studies were included to assess the impact of topotecan and veliparib on poly(ADP-ribose) levels in peripheral blood mononuclear cells, serum pharmacokinetics of both agents, and potential association of germline repair gene mutations with outcome. Experimental Design: Eligible patients had metastatic nonhematologic malignancies with measurable disease. Using a 3 + 3 design, patients were treated with veliparib orally twice daily on days 1–3, 8–10, and 15–17 and topotecan intravenously on days 2, 9, and 16 every 28 days. Tumor responses were assessed by RECIST. Results: Of 58 patients enrolled, 51 were evaluable for the primary endpoint. The MTD and RP2D was veliparib 300 mg twice daily on days 1–3, 8–10, and 15–17 along with topotecan 3 mg/m 2 on days 2, 9, and 16 of a 28-day cycle. DLTs were grade 4 neutropenia lasting >5 days. The median number of cycles was 2 (1–26). The objective response rate was 10%, with 1 complete and 4 partial responses. Twenty-two patients (42%) had stable disease ranging from 4 to 26 cycles. Patients with germline BRCA1, BRCA2 , or RAD51D mutations remained on study longer than those without homologous recombination repair (HRR) gene mutations (median 4 vs. 2 cycles). Conclusions: Weekly topotecan in combination with veliparib has a manageable safety profile and appears to warrant further investigation. Clin Cancer Res; 24(4); 744–52. ©2017 AACR .
Wahner Hendrickson, A. E., Menefee, M. E., Hartmann, L. C., Long, H. J., Northfelt, D. W., Reid, J. M., Boakye-Agyeman, F., Kayode, O., Flatten, K. S., Harrell, M. I., Swisher, E. M., Poirer, G. G., Satele, D., Allred, J., Lensing, J. L., Chen, A., Ji, J., Zang, Y., Erlichman, C., Haluska, P., Kaufmann, S. H.
The American Association for Cancer Research (AACR)
1078-0432
10780432
1557-3265
15573265
shingle_title_1 A Phase I Clinical Trial of the Poly(ADP-ribose) Polymerase Inhibitor Veliparib and Weekly Topotecan in Patients with Solid Tumors
shingle_title_2 A Phase I Clinical Trial of the Poly(ADP-ribose) Polymerase Inhibitor Veliparib and Weekly Topotecan in Patients with Solid Tumors
shingle_title_3 A Phase I Clinical Trial of the Poly(ADP-ribose) Polymerase Inhibitor Veliparib and Weekly Topotecan in Patients with Solid Tumors
shingle_title_4 A Phase I Clinical Trial of the Poly(ADP-ribose) Polymerase Inhibitor Veliparib and Weekly Topotecan in Patients with Solid Tumors
timestamp 2025-06-30T23:32:47.120Z
titel A Phase I Clinical Trial of the Poly(ADP-ribose) Polymerase Inhibitor Veliparib and Weekly Topotecan in Patients with Solid Tumors
titel_suche A Phase I Clinical Trial of the Poly(ADP-ribose) Polymerase Inhibitor Veliparib and Weekly Topotecan in Patients with Solid Tumors
topic WW-YZ
uid ipn_articles_6166100