Phase I trial of TRC102 (methoxyamine HCl) in combination with temozolomide in patients with relapsed solid tumors and lymphomas

Oncotarget
Geraldine O'Sullivan CoyneAlice P Chen

Abstract

TRC102 inhibits base excision repair by binding abasic sites and preventing AP endonuclease processing; it potentiates the activity of alkylating agents, including temozolomide, in murine models. In published xenograft studies, TRC102 enhanced the antitumor effect of temozolomide regardless of cell line genetic characteristics, e.g., O6-methylguanine DNA methyltransferase (MGMT), mismatch repair (MMR), or p53 status. We conducted a phase 1 trial of TRC102 with temozolomide given orally on days 1-5 of 28-day cycles in adult patients with refractory solid tumors that had progressed on standard therapy. Tumor induction of nuclear biomarkers of DNA damage response (DDR) γH2AX, pNBs1, and Rad51 was assessed in the context of MGMT and MMR protein expression for expansion cohort patients. Fifty-two patients were enrolled (37 escalation, 15 expansion) with 51 evaluable for response. The recommended phase 2 dose was 125 mg TRC102, 150 mg/m2 temozolomide QDx5. Common adverse events (grade 3/4) included anemia (19%), lymphopenia (12%), and neutropenia (10%). Four patients achieved partial responses (1 non-small cell lung cancer, 2 granulosa cell ovarian cancer, and 1 colon cancer) and 13 patients had a best response of stable disease. Ret...Continue Reading

References

Feb 24, 2001·Journal of Pharmaceutical and Biomedical Analysis·H KimA A Nomeir
May 24, 2003·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·R DziadziuszkoUNKNOWN EORTC Lung Cancer Group
Mar 11, 2005·The New England Journal of Medicine·Roger StuppUNKNOWN National Cancer Institute of Canada Clinical Trials Group
Mar 11, 2005·The New England Journal of Medicine·Monika E HegiRoger Stupp
Jan 24, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Lili Liu, Stanton L Gerson
Mar 3, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ling YanLili Liu
May 14, 2008·Anti-cancer Agents in Medicinal Chemistry·Ida CasorelliMargherita Bignami
Jan 2, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Matthew H KulkeMark S Redston
Jan 21, 2009·Cellular and Molecular Life Sciences : CMLS·A B RobertsonI Leiros
May 7, 2010·CA: a Cancer Journal for Clinicians·Erwin G Van MeirJeffrey J Olson
Jun 30, 2012·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Shuming YangYan Xu
Mar 12, 2013·Nucleic Acids Research·Timothy J TricheKimberly D Siegmund
Jan 1, 2014·Annals of Oncology : Official Journal of the European Society for Medical Oncology·F PietrantonioM Di Bartolomeo
Jun 21, 2014·Future Oncology·Mark R KelleyMelissa L Fishel
Jul 16, 2014·Trends in Genetics : TIG·Felix DietleinH Christian Reinhardt
Mar 24, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Apurva K SrivastavaRalph E Parchment
Oct 5, 2018·Journal of Oncology Practice·Katherine V Ferry-GalowAlice P Chen
Feb 23, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Deborah F WilskerRobert J Kinders
Jun 13, 2019·Journal of Hospital Management and Health Policy·Katherine V Ferry-Galow, Alice P Chen

❮ Previous
Next ❯

Citations

Jul 10, 2021·Signal Transduction and Targeted Therapy·Ruixue Huang, Ping-Kun Zhou

❮ Previous
Next ❯

Methods Mentioned

BETA
xenograft
biopsy
biopsies
RNA-seq

Clinical Trials Mentioned

NCT02243592
NCT01851369

Software Mentioned

R package
SeSAMe
IDAT

Related Concepts

Related Feeds

Anemia

Anemia develops when your blood lacks enough healthy red blood cells. Anemia of inflammation (AI, also called anemia of chronic disease) is a common, typically normocytic, normochromic anemia that is caused by an underlying inflammatory disease. Here is the latest research on anemia.

Related Papers

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Christina K AugustineDouglas S Tyler
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
D S MiddlemasT P Brent
American Journal of Health-system Pharmacy : AJHP : Official Journal of the American Society of Health-System Pharmacists
© 2021 Meta ULC. All rights reserved