Assessing the Response Rate of Neo-adjuvant Taxotere and Trastuzumab in Nigerian Women With Breast Cancer

Study Overview
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Brief Summary
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This is a one stage phase II study with a single arm design. It will be conducted in HER-2 positive breast cancer patients in Nigeria who are chemotherapy/hormonal treatment naive.

Official Title
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Assessing REsponse to Neoadjuvant Taxotere and Trastuzumab in Nigerian Women With HER2-positive Breast Cancer (ARETTA)

Conditions
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Breast Cancer, Breast Cancer Female, HER2-positive Breast Cancer, Breast Cancer Stage II, Breast Cancer Stage III

Intervention / Treatment
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* Drug: Docetaxel
* Drug: Herceptin
* Drug: FEC
* Drug: Tamoxifen
* Drug: Letrozole
* Drug: LHRH agonist


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women ages of 18 to 70 years old Biopsy-accessible breast tumor of significant size for core needle biopsy/ultrasound measurable (≥ 2cm) Patients with histologically confirmed carcinoma of the female breast with 3+ positive HER2 status by IHC Clinical stages IIA -IIIC (AJCC 2009) Chemotherapy-naïve patients (for this malignancy) Performance status: ECOG performance status 0-1 (Appendix A) Non-pregnant and not nursing. Women of childbearing potential must take the pregnancy test and must commit to receive LHRH agonist Zoladex (goserelin) for two years starting from the commencement of the study medications Required Initial Laboratory Data. Adequate hematologic, renal and hepatic function, as defined by each of the following: 1. Granulocyte ≥ 1,500/μL 2. Platelet count ≥ 100,000/μL 3. Absolute neutrophil count (ANC) ≥ l500/μL 4. Hemoglobin ≥ 10g/dL 5. Bilirubin ≤ 1.5 x upper limit of normal 6. SGOT and SGPT < 2.5 x upper limit of normal 7. Creatinine within institutional normal limits or glomerular filtration rate ≥ 30 mL/min/1.73 m2 by CKD EPI equation (see http://mdrd.com/ for calculator) 9. ECHO: Baseline left ventricular ejection fraction of ≥ 55% Exclusion Criteria: Pregnant or lactating women. Women of childbearing potential not using a reliable and appropriate contraceptive method. Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential. Patients of childbearing potential will agree to continue the use of acceptable form of contraception for 24 months from the date of last Herceptin administration. Patients with distant metastasis (brain and/or visceral metastasis) Serious, uncontrolled, concurrent infection(s). Treatment for other carcinomas within the last 5 years, except non-melanoma skin cancer and treated cervical carcinoma in-situ (CCIS) Participation in any investigational drug study within 4 weeks preceding the start of study treatment Other serious uncontrolled medical conditions that the investigator feels might compromise study participation including but not limited to chronic or active infection, HIV-positive patient, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled Diabetes mellitus, or psychiatric illness/social situations that would limit compliance with study requirements. Patients with HER2-negative disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Docetaxel<br>Investigators will give patients docetaxel through drip every 3 weeks for four doses for 12 weeks before a repeat breast ultrasound. After breast ultrasound, if the investigator feels the injection is good, surgery will be done. | Drug: Docetaxel<br>* Administered to all patients for a minimum of 4 cycles for 12 weeks.<br>|
| Other: Herceptin<br>Herceptin will be given to patients under the skin of the thigh every 3 weeks for 18 times if they are HER2-positive | Drug: Herceptin<br>* Administered for 18 cycles every three weeks (52 weeks) for each patient starting at the first day of treatment with docetaxel.<br>* Other names: Trastuzumab;|
| Other: Fluorouracil Epirubicin Hydrochloride Cyclophonsphamide (FEC)<br>Patients with a poor response to docetaxal will receive FEC injection by drip every 3 weeks. | Drug: FEC<br>* Only administered to patients who received docetaxel and herceptin and were assessed as having poor response (defined as stable disease or progressive disease or partial response inoperable).<br>|
| Other: LHRH (luteinizing hormone-releasing hormone)<br>All Premenopausal patients will receive LHRH agonist for two years every 3 months for contraception and fertility preservation. | Drug: LHRH agonist<br>* Administered to all premenopausal patients.<br>|
| Other: Tamoxifen or letrozole<br>Hormone-receptor positive patients will receive hormonal therapy with tamoxifen or letrozole after surgery, radiotherapy and LHRH agonist according to the expression of hormone receptors and according to the state of primary menopause at the onset of the study. | Drug: Tamoxifen<br>* Only administered to hormone-receptor positive patients. Patients will receive tamoxifen or letrozole.<br>Drug: Letrozole<br>* Only administered to hormone-receptor positive patients. Patients will receive tamoxifen or letrozole.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure the complete pathologic response (pCR) | Pathological complete response in the breast is defined as the absence of invasive cells at microscopic examination of the primary tumor and lymph nodes at surgery. Any remaining in-situ lesions are permissible. Participants with invalid/missing pCR assessments will be defined as non-responders. | 4-6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events | Incidence and severity of adverse drug reactions (AE) and serious adverse drug reactions (SAE) including clinical laboratory values, vital signs, ECGs and dose interruptions. | 4-6 months | 
| Time until progression free survival (PFS) |  | From start date of therapy to the date of first documented disease progression or death from any cause, whichever may come first, assessed up to 10 years | 
| Duration of response (DOR) |  | From first reponse to the date of first documented disease progression or death, assessed up to 10 years | 
| Analysis of changes from baseline using the quality of life (QoL) instrument: EORTC | The various domains of QoL over time and the changes from baseline using the validated (by the European Organization for Research and Treatment of Cancer (EORTC)) QoL instrument (global and breast module). | From start date of therapy to the date of first documented disease progression or death from any cause, whichever may come first, assessed up to 10 years | 
| Blood concentrations of Herceptin SC given in combination with Docetaxel | Blood concentrations of Herceptin SC at multiple time points using the peak exposure | 21 days | 
| Drug plasma concentration of Herceptin SC given in combination with FEC | Determine the pharmacokinetic profile of Herceptin SC given in combination with FEC following poor response to TH | 21 days | 
| The cardiac toxicity associated with TscH with FEC +scH in breast cancer patients | The percentage of participants with Heart failure (NYHA Class III or IV or as confirmed by a cardiologist) and a decrease in LVEF of at least 10 EF points from baseline and to below 50%. | Through study completion an average of two years | 
| The cardiac toxicity associated with TscH without FEC +scH in breast cancer patients | The percentage of participants with Heart failure (NYHA Class III or IV or as confirmed by a cardiologist) and a decrease in LVEF of at least 10 EF points from baseline and to below 50%. | Through study completion an average of two years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, breast cancer stage II, Breast Cancer Stage III, Docetaxel, Herceptin, neoadjuvant treatment, nigeria