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Breast CancerPhase 2TCHL Phase IINCT01485926

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 Phase 2 study testing Docetaxel, Carboplatin and Trastuzumab and Docetaxel, Carboplatin, Trastuzumab and Lapatinib in people with Breast Cancer, run by Cancer Trials Ireland at 11 sites in Ireland.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Cancer
What is being tested?
Docetaxel, Carboplatin and Trastuzumab and Docetaxel, Carboplatin, Trastuzumab and Lapatinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
120 participants
Where
11 sitesIreland
Study dates
Oct 2010to May 2018
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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.
  • Formalin-fixed paraffin-embedded tissue available from diagnostic biopsy and/or definitive surgical intervention
  • -Where possible fresh frozen tissue will be sought as outlined per protocol.
  • Adequate bone marrow function within 14 days prior to randomisation as defined by the following laboratory values
  • Absolute neutrophil count ≥ 1.0 x 10^9/L
  • Haemoglobin ≥ 9.0 g/dL
  • Platelet count ≥ 100 x 10^9/L
  • Adequate renal function within 14 days prior to randomisation as defined by:
  • Serum creatinine < or equal to 1.25 x upper limit of normal (ULN), defined by institution
  • Serum creatinine clearance of > 60 mg/ml/min
  • Adequate hepatic function within 14 days prior to randomisation as defined by:
  • Total bilirubin < or equal to 1.0 x upper limit of normal (ULN). Patients with Gilbert's syndrome prior to study entry must have total bilirubin <3X ULN.
  • Alkaline phosphatase and AST/ALT within parameters specified by protocol.
  • Able to swallow and retain oral medication
  • Patients must be deemed potentially operable following neo-adjuvant treatment.

Who cannot join

  • 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.
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  • 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.
  • Patients with known hypersensitivity to Chinese hamster ovary products or other recombinant human or humanized antibodies and/or known hypersensitivity to any of the study drugs or their ingredients (eg, polysorbate 80 in docetaxel)
  • Pregnant women are excluded from this study because lapatinib is member of the 4-anilinoquinazoline class of kinase inhibitors with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with lapatinib, breastfeeding should be discontinued if the mother is treated with lapatinib
  • HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with lapatinib. Appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated.
  • Patients with GI tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative colitis).
  • Concomitant requirement for medication classified as CYP3A4 inducers or inhibitors as defined in Table 2.
  • Have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

Ireland11 sites

  • Bon Secours Hospital

    Cork

  • Cork University Hospital

    Cork

  • St James's Hospital

    Dublin, Leinster

  • St Vincent's University Hospital

    Dublin, Leinster

  • Beaumont Hospital

    Dublin

  • Mater Misericordiae University and Private Hospitals

    Dublin

  • Galway University Hospital

    Galway

  • Letterkenny General Hospital

    Letterkenny

  • Mid-Western Regional Hospital

    Limerick

  • Sligo General Hospital

    Sligo

  • Waterford Regional Hospital

    Waterford

Other trials in Ireland

About this study

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).

Read more

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
Being tested
Docetaxel, Carboplatin and Trastuzumab, Docetaxel, Carboplatin, Trastuzumab and Lapatinib
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Docetaxel, Carboplatin and TrastuzumabDrug

    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, Trastuzumab and LapatinibDrug

    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.

Study groups in NCT01485926
Study groupRoleWhat they receive
Docetaxel, Carboplatin and TrastuzumabExperimentalArm 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.
Receives: Drug: Docetaxel, Carboplatin and Trastuzumab
Docetaxel, Carboplatin, Trastuzumab and LapatinibExperimentalArm 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.
Receives: Drug: Docetaxel, Carboplatin, Trastuzumab and Lapatinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. pathological complete response

    Measured: 5 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Dec 2011 (estimated)
  2. Study startOct 2010
  3. Primary completionSep 2014
  4. Study completionMay 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
120 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01485926
Sponsor's protocol ID
CTRIAL-IE (ICORG) 10-05
Acronym
TCHL Phase II
Status last verified
Aug 2018
First submitted
2 Dec 2011
Last updated
6 Aug 2018
Results posted
No
Data monitoring committee
No

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.

    PubMed 40468999

  • 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.

    PubMed 37507543

  • 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.

    PubMed 28750640

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Docetaxel, Carboplatin and Trastuzumab and Docetaxel, Carboplatin, Trastuzumab and Lapatinib in people with Breast Cancer, run by Cancer Trials Ireland at 11 sites in Ireland.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 29 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in Ireland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

pathological complete response (time frame: 5 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01485926, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2018.

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