Tucatinib, Trastuzumab, and Capecitabine With SRS for Brain Metastases From HER-2 Positive Breast Cancer

Summary

This research study will evaluate how well brain metastases associated with HER-2 positive breast cancer can be controlled using a type of radiation known as stereotactic radiosurgery (SRS) when combined with three therapeutic agents, tucatinib, capecitabine, and trastuzumab. The combined use of SRS with the three drugs is considered investigational.

Timeline

Start

2024-01-29

Primary completion

2025-12-17

Completion

2025-12-17

Publications

• Background Ahluwalia MS, Vogelbaum MV, Chao ST, Mehta MM. Brain metastasis and treatment. F1000Prime Rep. 2014 Dec 1;6:114. doi: 10.12703/P6-114. eCollection 2014.
• Background Moulder SL, Borges VF, Baetz T, Mcspadden T, Fernetich G, Murthy RK, Chavira R, Guthrie K, Barrett E, Chia SK. Phase I Study of ONT-380, a HER2 Inhibitor, in Patients with HER2+-Advanced Solid Tumors, with an Expansion Cohort in HER2+ Metastatic Breast Cancer (MBC). Clin Cancer Res. 2017 Jul 15;23(14):3529-3536. doi: 10.1158/1078-0432.CCR-16-1496. Epub 2017 Jan 4.
• Background Morikawa A, Peereboom DM, Thorsheim HR, Samala R, Balyan R, Murphy CG, Lockman PR, Simmons A, Weil RJ, Tabar V, Steeg PS, Smith QR, Seidman AD. Capecitabine and lapatinib uptake in surgically resected brain metastases from metastatic breast cancer patients: a prospective study. Neuro Oncol. 2015 Feb;17(2):289-95. doi: 10.1093/neuonc/nou141. Epub 2014 Jul 11.
• Background Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, Jagiello-Gruszfeld A, Crown J, Chan A, Kaufman B, Skarlos D, Campone M, Davidson N, Berger M, Oliva C, Rubin SD, Stein S, Cameron D. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006 Dec 28;355(26):2733-43. doi: 10.1056/NEJMoa064320.
• Background Pheneger T, Bouhana K, Anderson D, Garrus J, Ahrendt K, Allen S, et al. In Vitro and in vivo activity of ARRY-380: A potent, small molecule inhibitor of ErbB2. AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO. Abstract #1795.
• Background Murthy R, Borges VF, Conlin A, Chaves J, Chamberlain M, Gray T, Vo A, Hamilton E. Tucatinib with capecitabine and trastuzumab in advanced HER2-positive metastatic breast cancer with and without brain metastases: a non-randomised, open-label, phase 1b study. Lancet Oncol. 2018 Jul;19(7):880-888. doi: 10.1016/S1470-2045(18)30256-0. Epub 2018 May 24.
• Background Lin NU, Borges V, Anders C, Murthy RK, Paplomata E, Hamilton E, Hurvitz S, Loi S, Okines A, Abramson V, Bedard PL, Oliveira M, Mueller V, Zelnak A, DiGiovanna MP, Bachelot T, Chien AJ, O'Regan R, Wardley A, Conlin A, Cameron D, Carey L, Curigliano G, Gelmon K, Loibl S, Mayor J, McGoldrick S, An X, Winer EP. Intracranial Efficacy and Survival With Tucatinib Plus Trastuzumab and Capecitabine for Previously Treated HER2-Positive Breast Cancer With Brain Metastases in the HER2CLIMB Trial. J Clin Oncol. 2020 Aug 10;38(23):2610-2619. doi: 10.1200/JCO.20.00775. Epub 2020 May 29.
• Background Brown PD, Jaeckle K, Ballman KV, Farace E, Cerhan JH, Anderson SK, Carrero XW, Barker FG 2nd, Deming R, Burri SH, Menard C, Chung C, Stieber VW, Pollock BE, Galanis E, Buckner JC, Asher AL. Effect of Radiosurgery Alone vs Radiosurgery With Whole Brain Radiation Therapy on Cognitive Function in Patients With 1 to 3 Brain Metastases: A Randomized Clinical Trial. JAMA. 2016 Jul 26;316(4):401-409. doi: 10.1001/jama.2016.9839.
• Background Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987 Jan 9;235(4785):177-82. doi: 10.1126/science.3798106.
• Background Aragon-Ching JB, Zujewski JA. CNS metastasis: an old problem in a new guise. Clin Cancer Res. 2007 Mar 15;13(6):1644-7. doi: 10.1158/1078-0432.CCR-07-0096.
• Background Sperduto PW, Kased N, Roberge D, Xu Z, Shanley R, Luo X, Sneed PK, Chao ST, Weil RJ, Suh J, Bhatt A, Jensen AW, Brown PD, Shih HA, Kirkpatrick J, Gaspar LE, Fiveash JB, Chiang V, Knisely JP, Sperduto CM, Lin N, Mehta M. Summary report on the graded prognostic assessment: an accurate and facile diagnosis-specific tool to estimate survival for patients with brain metastases. J Clin Oncol. 2012 Feb 1;30(4):419-25. doi: 10.1200/JCO.2011.38.0527. Epub 2011 Dec 27.
• Background Brufsky AM, Mayer M, Rugo HS, Kaufman PA, Tan-Chiu E, Tripathy D, Tudor IC, Wang LI, Brammer MG, Shing M, Yood MU, Yardley DA. Central nervous system metastases in patients with HER2-positive metastatic breast cancer: incidence, treatment, and survival in patients from registHER. Clin Cancer Res. 2011 Jul 15;17(14):4834-43. doi: 10.1158/1078-0432.CCR-10-2962.
• Background Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA, Swain SM, Pisansky TM, Fehrenbacher L, Kutteh LA, Vogel VG, Visscher DW, Yothers G, Jenkins RB, Brown AM, Dakhil SR, Mamounas EP, Lingle WL, Klein PM, Ingle JN, Wolmark N. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005 Oct 20;353(16):1673-84. doi: 10.1056/NEJMoa052122.
• Background Baselga J, Cortes J, Kim SB, Im SA, Hegg R, Im YH, Roman L, Pedrini JL, Pienkowski T, Knott A, Clark E, Benyunes MC, Ross G, Swain SM; CLEOPATRA Study Group. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012 Jan 12;366(2):109-19. doi: 10.1056/NEJMoa1113216. Epub 2011 Dec 7.
• Background Pestalozzi BC, Brignoli S. Trastuzumab in CSF. J Clin Oncol. 2000 Jun;18(11):2349-51. doi: 10.1200/JCO.2000.18.11.2349. No abstract available.
• Background Rusnak DW, Lackey K, Affleck K, Wood ER, Alligood KJ, Rhodes N, Keith BR, Murray DM, Knight WB, Mullin RJ, Gilmer TM. The effects of the novel, reversible epidermal growth factor receptor/ErbB-2 tyrosine kinase inhibitor, GW2016, on the growth of human normal and tumor-derived cell lines in vitro and in vivo. Mol Cancer Ther. 2001 Dec;1(2):85-94.
• Background Leone JP, Lee AV, Brufsky AM. Prognostic factors and survival of patients with brain metastasis from breast cancer who underwent craniotomy. Cancer Med. 2015 Jul;4(7):989-94. doi: 10.1002/cam4.439. Epub 2015 Mar 9.
• Sarfraz Z, Ozair A, Bardhan M, Starosciak AK, Perche DC, Hodgson LC, Odia Y, Mehta MP, Kotecha R, McDermott MW, Maharaj A, Leon ACS, Mahtani R, Ahluwalia MS. Tucatinib, trastuzumab, and capecitabine with stereotactic radiosurgery in patients with brain metastases from HER-2 positive breast cancer (TUTOR): Study protocol for a multicenter phase 1 clinical trial. BMC Cancer. 2025 Dec 4;26(1):43. doi: 10.1186/s12885-025-15224-3.

Drugs

Indications