A Phase II Neo-adjuvant Study Assessing TCH (Docetaxel, Carboplatin and Trastuzumab) and TCHL (Docetaxel, Carboplatin, Trastuzumab and Lapatinib) in HER-2 Positive Breast Cancer Patients.
Summary
The primary objective: -To assess the efficacy of TCH and TCHL in neo-adjuvant treatment of HER-2 positive breast cancer, using pathological complete response (pCR) as the primary endpoint (Phase II). Secondary objectives: * To assess the clinical response rate and overall response rate for docetaxel and carboplatin with trastuzumab alone or trastuzumab combined with lapatinib in HER-2 positive breast cancer. * To assess the relationship between drug exposure and adverse events. * To examine potential molecular and pharmacological markers of response to trastuzumab and lapatinib * To assess Disease-free Survival (DFS) and Overall Survival (OS) * To determine if prophylactic Loperamide significantly reduces the number of diarrhoea -related adverse events.
Timeline
- Start
- 2010-10
- Primary completion
- 2014-09
- Completion
- 2018-05
Outcome
Missed primary endpoint
paper The study did not meet its primary endpoint of superior pCR. PMID 40468999 ↗
paper The pCR rates for TCH and TCHL were 52.8 and 51.6 (p = 1.0). PMID 40468999 ↗
Publications
- Crown J, Eustace AJ, Collins DM, Keane M, Coate L, Kennedy J, O'Reilly S, Kelly C, O'Connor M, Martin M, Murphy C, Duffy K, Walshe J, Gullo G, Mahgoub T, Alvarez-Iglesias A, Parker I, Donachie V, Teiserskiene A, Madden SF, Moulton B, O'Donovan N, Hennessy BT. TCHL - a phase II neo-adjuvant study assessing TCH (docetaxel, carboplatin and trastuzumab) and TCHL (docetaxel, carboplatin, trastuzumab and lapatinib) in HER-2 positive breast cancer patients: a 5-year follow-up with serum biomarker analysis. Acta Oncol. 2025 Jun 5;64:751-760. doi: 10.2340/1651-226X.2025.43143.
- Gaynor N, Blanco A, Madden SF, Moran B, Fletcher JM, Kaukonen D, Ramirez JS, Eustace AJ, McDermott MSJ, Canonici A, Toomey S, Teiserskiene A, Hennessy BT, O'Donovan N, Crown J, Collins DM. Alterations in immune cell phenotype and cytotoxic capacity in HER2+ breast cancer patients receiving HER2-targeted neo-adjuvant therapy. Br J Cancer. 2023 Oct;129(6):1022-1031. doi: 10.1038/s41416-023-02375-y. Epub 2023 Jul 28.
- Toomey S, Eustace AJ, Fay J, Sheehan KM, Carr A, Milewska M, Madden SF, Teiserskiene A, Kay EW, O'Donovan N, Gallagher W, Grogan L, Breathnach O, Walshe J, Kelly C, Moulton B, Kennedy MJ, Gullo G, Hill AD, Power C, Duke D, Hambly N, Crown J, Hennessy BT. Impact of somatic PI3K pathway and ERBB family mutations on pathological complete response (pCR) in HER2-positive breast cancer patients who received neoadjuvant HER2-targeted therapies. Breast Cancer Res. 2017 Jul 27;19(1):87. doi: 10.1186/s13058-017-0883-9.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Carboplatin | Small molecule | 6 unknown | — |
| Subject | Docetaxel | Small molecule | 75 mg/m2 | — |
| Subject | Lapatinib | Small molecule | 1000 mg | — |
| Subject | Trastuzumab | Monoclonal antibody | 6 mg/kg | — |