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.

NCT01485926 | Completed Phase 2

• 1 other identifier: CTRIAL-IE (ICORG) 10-05
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 11

Brief 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.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• pathological complete response

  5 months

Study Arms (2)

Docetaxel, Carboplatin and Trastuzumab

EXPERIMENTAL

Arm A- 6 cycles q3weekly Docetaxel (75mg/m²) + Carboplatin (AUC 6) + Trastuzumab 8 mg/kg on day 1 (loading dose) and 6mg/kg for subsequent cycles, q3weekly thereafter. Patients will be scheduled for surgery and will continue to receive Trastuzumab post-operatively 6 mg/kg for one year from 1st dose of Trastuzumab.

Drug: Docetaxel, Carboplatin and Trastuzumab

Docetaxel, Carboplatin, Trastuzumab and Lapatinib

EXPERIMENTAL

Arm B - 6 cycles q3weekly Docetaxel (75mg/m²) + Carboplatin (AUC 6) + Trastuzumab (8 mg/kg on day 1 (loading dose) and 6mg/kg for subsequent cycles, q3weekly thereafter.) + Lapatinib (1000mg daily) until 1 week prior to surgery. Patients will be scheduled for surgery and will continue to receive Trastuzumab post-operatively 6 mg/kg for one year from 1st dose of Trastuzumab.

Drug: Docetaxel, Carboplatin, Trastuzumab and Lapatinib

Interventions

Docetaxel, Carboplatin and Trastuzumab DRUG

6 cycles q3weekly Docetaxel (75mg/m²) + Carboplatin (AUC 6) + Trastuzumab 8 mg/kg on day 1 (loading dose) and 6mg/kg for subsequent cycles, q3weekly thereafter. Patients will be scheduled for surgery and will continue to receive Trastuzumab post-operatively 6 mg/kg for one year from 1st dose of Trastuzumab.

Docetaxel, Carboplatin and Trastuzumab

Docetaxel, Carboplatin, Trastuzumab and Lapatinib DRUG

6 cycles q3weekly Docetaxel (75mg/m²) + Carboplatin (AUC 6) + Trastuzumab (8 mg/kg on day 1 (loading dose) and 6mg/kg for subsequent cycles, q3weekly thereafter.) + Lapatinib (1000mg daily) until 1 week prior to surgery. Patients will be scheduled for surgery and will continue to receive Trastuzumab post-operatively 6 mg/kg for one year from 1st dose of Trastuzumab.

Docetaxel, Carboplatin, Trastuzumab and Lapatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent obtained prior to any study-related procedures
• Age \> 18 years
• Histologically proven breast cancer, for which neo-adjuvant chemotherapy and trastuzumab is considered a valid therapeutic strategy.
• Patients with the following TNM stages (refer to AJCC 7th Edition - Appendix M) of breast cancer are eligible:
• T2, T3, T4a, T4b, T4c, T4d which is node negative or node positive (histologically or cytologically confirmed) or
• Any T with lymph node positive disease (histologically or cytologically confirmed)
• Patients with multifocal tumours are not excluded; T stage assignment must be based on the largest tumour.
• Patients presenting with bilateral breast cancer are not eligible
• Tumour HER2/neu positive (3+ by IHC or fluorescence in situ hybridization (FISH) positive)
• Oestrogen and progesterone receptor status known prior to study entry
• ECOG performance status score \< or equal to 1
• Cardiac ejection fraction ≥ 50% as measured by echocardiogram or MUGA scan within 3 months prior to randomisation. Note that baseline and on treatment scans should be performed using the same modality and preferably at the same institution
• The effects of lapatinib on the developing human foetus at the recommended therapeutic dose are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (non-hormonal or barrier method of birth control, abstinence or a vasectomy partner) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• If applicable, post-menopausal status will be defined as patients who are amenorrheic for \> 1 year or for a shorter duration if FSH, LH and/or oestradiol levels are within the post-menopausal range
• Patient is accessible and willing to comply with treatment, tissue acquisition and follow up.

You may not qualify if:

• Prior therapy with systemic cytotoxic chemotherapy Lapatinib or Trastuzumab.
• Prior taxanes
• Radiotherapy (Except for radiotherapy localised to radiotherapy to a primary squamous or basal cell skin cancer).
• Patients with metastatic disease (M1).
• Concurrent therapy with any other non-protocol anti-cancer therapy
• History of any other malignancy within the past 5 years, with the exception of non-melanoma skin cancer, in situ carcinoma of the breast (ductal or lobular) or carcinoma-in-situ of the cervix.
• Current therapy with any hormonal agent such as raloxifene, tamoxifen, or other selective oestrogen receptor modulators (SERMs), either for osteoporosis or prevention of breast cancer. Patients must have discontinued these agents 14 days prior to enrolment.
• Concurrent treatment with ovarian hormonal replacement therapy. Prior treatment must be stopped prior to enrolment.
• Pre-existing motor or sensory neurotoxicity of a severity ≥ Grade 2 by NCI-CTCAE version 4.0.
• Poorly controlled hypertension (e.g. systolic \>180mm Hg or diastolic \>100mm Hg.)
• Any history of myocardial infarction, angina pectoris or congestive heart failure. Patients on current therapy for arrythmias are excluded. For other patients with a history of self-limiting cardiac dieases (e.g. pericarditis, temporary secondary arrythmias) more than 1 year must have past prior to enrolment on the study
• Inflammatory bowel disease or other bowel condition causing chronic diarrhoea, requiring active therapy.
• Active, uncontrolled infection requiring parenteral antimicrobials or any condition requiring maintenance therapeutic (i.e. non-replacement) doses of corticosteroids.
• The presence of any other medical or psychiatric disorder that, in the opinion of the treating physician, would contraindicate the use of the drugs in this protocol or place the patient at undue risk for treatment complications
• Male patients.

Sponsors & Collaborators

• Cancer Trials Ireland: lead

Study Sites (11)

St James's Hospital

Dublin, Leinster, Ireland

Location

St Vincent's University Hospital

Dublin, Leinster, Ireland

Location

Bon Secours Hospital

Cork, Ireland

Location

Cork University Hospital

Cork, Ireland

Location

Beaumont Hospital

Dublin, Ireland

Location

Mater Misericordiae University and Private Hospitals

Dublin, Ireland

Location

Galway University Hospital

Galway, Ireland

Location

Letterkenny General Hospital

Letterkenny, Ireland

Location

Mid-Western Regional Hospital

Limerick, Ireland

Location

Sligo General Hospital

Sligo, Ireland

Location

Waterford Regional Hospital

Waterford, Ireland

Location

Related Publications (3)

• 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.

  PMID: 40468999 DERIVED

• 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.

  PMID: 37507543 DERIVED

• 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.

  PMID: 28750640 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Docetaxel; Carboplatin; Trastuzumab; Lapatinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2011
• First Posted: December 6, 2011
• Study Start: October 1, 2010
• Primary Completion: September 1, 2014
• Study Completion: May 1, 2018
• Last Updated: August 6, 2018

Record last verified: 2018-08

Locations

IE (11)