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. (TCHL Phase II)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
ICORG- All Ireland Cooperative Oncology Research Group
ClinicalTrials.gov Identifier:
NCT01485926
First received: December 2, 2011
Last updated: February 3, 2014
Last verified: January 2014
  Purpose

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.

Condition Intervention Phase
Breast Cancer
Drug: Docetaxel, Carboplatin and Trastuzumab
Drug: Docetaxel, Carboplatin, Trastuzumab and Lapatinib
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by ICORG- All Ireland Cooperative Oncology Research Group:

Primary Outcome Measures:
  • pathological complete response [ Time Frame: 5 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 120
Study Start Date: October 2010
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Docetaxel, Carboplatin and Trastuzumab
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
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.
Experimental: Docetaxel, Carboplatin, Trastuzumab and Lapatinib
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
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Written informed consent obtained prior to any study-related procedures
  2. Age > 18 years
  3. Histologically proven breast cancer, for which neo-adjuvant chemotherapy and trastuzumab is considered a valid therapeutic strategy.
  4. 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
  5. Tumour HER2/neu positive (3+ by IHC or fluorescence in situ hybridization (FISH) positive)
  6. Oestrogen and progesterone receptor status known prior to study entry
  7. ECOG performance status score < or equal to 1
  8. 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
  9. 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

  10. Patient is accessible and willing to comply with treatment, tissue acquisition and follow up.
  11. 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.

  12. Adequate bone marrow function within 14 days prior to randomisation as defined by the following laboratory values

    1. Absolute neutrophil count ≥ 1.0 x 10^9/L
    2. Haemoglobin ≥ 9.0 g/dL
    3. Platelet count ≥ 100 x 10^9/L
  13. Adequate renal function within 14 days prior to randomisation as defined by:

    1. Serum creatinine < or equal to 1.25 x upper limit of normal (ULN), defined by institution
    2. Serum creatinine clearance of > 60 mg/ml/min
  14. Adequate hepatic function within 14 days prior to randomisation as defined by:

    1. 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.
    2. Alkaline phosphatase and AST/ALT within parameters specified by protocol.
  15. Able to swallow and retain oral medication
  16. Patients must be deemed potentially operable following neo-adjuvant treatment.

Exclusion Criteria:

  1. Prior therapy with systemic cytotoxic chemotherapy Lapatinib or Trastuzumab.
  2. Prior taxanes
  3. Radiotherapy (Except for radiotherapy localised to radiotherapy to a primary squamous or basal cell skin cancer).
  4. Patients with metastatic disease (M1).
  5. Concurrent therapy with any other non-protocol anti-cancer therapy
  6. 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.
  7. 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.
  8. Concurrent treatment with ovarian hormonal replacement therapy. Prior treatment must be stopped prior to enrolment.
  9. Pre-existing motor or sensory neurotoxicity of a severity ≥ Grade 2 by NCI-CTCAE version 4.0.
  10. Poorly controlled hypertension (e.g. systolic >180mm Hg or diastolic >100mm Hg.)
  11. 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
  12. Inflammatory bowel disease or other bowel condition causing chronic diarrhoea, requiring active therapy.
  13. Active, uncontrolled infection requiring parenteral antimicrobials or any condition requiring maintenance therapeutic (i.e. non-replacement) doses of corticosteroids.
  14. 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
  15. Male patients.
  16. 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)
  17. 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
  18. 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.
  19. 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).
  20. Concomitant requirement for medication classified as CYP3A4 inducers or inhibitors as defined in Table 2.
  21. 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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01485926

Locations
Ireland
St James's Hospital
Dublin, Leinster, Ireland
St Vincent's University Hospital
Dublin, Leinster, Ireland
Cork University Hospital
Cork, Ireland
Bon Secours Hospital
Cork, Ireland
Beaumont Hospital
Dublin, Ireland
Mater Misericordiae University and Private Hospitals
Dublin, Ireland
Galway University Hospital
Galway, Ireland
Letterkenny General Hospital
Letterkenny, Ireland
Mid-Western Regional Hospital
Limerick, Ireland
Sligo General Hospital
Sligo, Ireland
Waterford Regional Hospital
Waterford, Ireland
Sponsors and Collaborators
ICORG- All Ireland Cooperative Oncology Research Group
  More Information

No publications provided

Responsible Party: ICORG- All Ireland Cooperative Oncology Research Group
ClinicalTrials.gov Identifier: NCT01485926     History of Changes
Other Study ID Numbers: ICORG 10-05
Study First Received: December 2, 2011
Last Updated: February 3, 2014
Health Authority: Ireland: Irish Medicines Board

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Docetaxel
Trastuzumab
Lapatinib
Carboplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 20, 2014