Neoadjuvant Goserelin for Triple Negative Breast Cancer

Study Overview
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Brief Summary
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This is a phase II randomized trial that will evaluate the effect of adding LHRH analogue, goserelin, to the standard neoadjuvant chemotherapy to patients with triple negative breast cancer. Targeting LHRH might decrease resistance to chemotherapeutic agents in the neoadjuvant setting and increases clinical and pathological response rates. Additionally, exploring potential surrogate markers (as AR and LHRH receptors) for molecular distinct subtypes of TNBC.

Detailed Description
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Neoadjuvant chemotherapy (NACT) is the mainstay of treatment of locally advanced TNBC and some selected early cases followed by surgery with or without adjuvant radiotherapy. NACT is aimed to induce pathologic complete response (pCR) in tumor and lymph nodes, pCR is proofed to be a surrogate and reliable predictive factor of survival rates in TNBC. This study will evaluate the effect of adding LHRH analogue, goserelin, to the standard neoadjuvant chemotherapy. Following completion of neoadjuvant therapy, patients will undergo breast conservative surgery or mastectomy. Post-neoadjuvant chemotherapy axillary staging will be required, but the choice of the procedure will be at the physician's discretion. Postoperative radiation therapy will be given at the physician's discretion. The use of partial breast irradiation techniques will not be allowed. The primary endpoint will be the rate of pathologic complete response. The secondary endpoints will be 3-year-disease free survival, clinical response and toxicity. Exploratory endpoints will be correlation of the LHRH receptor expression level with the pCR. The sample size for the trial will be 180 patients accrued over a period of 2 years. Definitive analysis of the primary endpoints is expected at year 3.

Official Title
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Prospective Phase II Randomized Trial of Evaluating the Effect of Adding LHRH Analogue to the Neoadjuvant Chemotherapy Treatment of Triple Negative Breast Cancer on Pathologic Complete Response (pCR) Rates

Conditions
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Breast Cancer Triple Negative

Intervention / Treatment
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* Drug: Goserelin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Premenopausal women between 18 and 60 years. Histologically proven, newly diagnosed invasive carcinoma of breast. Tumors must be ER, PgR negative and HER2-neu negative. Stage II or III breast cancer that is indicated for neoadjuvant systemic chemotherapy. Exclusion Criteria: pregnant females at time of diagnosis of breast cancer. bilateral breast cancer. already received treatment for breast cancer including surgery, radiation, cytotoxic, or endocrine therapy history or concomitant diagnosis of another primary malignancy. concurrent treatment with oral contraceptives or hormone replacement therapy (OCPs or HRT must be stopped at least 4 weeks prior to randomization).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>Goserelin 3.6 mg depot injection will be administered subcutaneously every month along with standard chemotherapy regimen: AC-P: Doxorubicin 60 mg/m2 IV plus cyclophosphamide 600 mg/m2 every 3 weeks for four cycles, followed by paclitaxel 80 mg/m2 by 1 hour infusion every week for 12 weeks. Each cycle is 21 days. | Drug: Goserelin<br>* Goserelin is Luteinizing hormone releasing hormone (LHRH) analogue.<br>* Other names: Zoladex;|
| No Intervention: Group B<br>Standard chemotherapy regimen: AC-P: Doxorubicin 60 mg/m2 IV plus cyclophosphamide 600 mg/m2 every 3 weeks for four cycles, followed by paclitaxel 80 mg/m2 by 1 hour infusion every week for 12 weeks. Each cycle is 21 days. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pathologic complete response rate | The primary endpoint will be the pathologic complete response rate (pCR), defined as no residual invasive tumor in both the breast and axilla (and including in situ residual; ypT0/is, ypN0). | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LHRH-positive and/or AR-positive Rate | Incidence of LHRH-positive and/or AR-positive cases among TNBC | 6 months | 
| Relapse-free Survival | Estimated 3 years RFS rates in the 2 arms (RFS events will include locoregional recurrence, distant recurrence, contralateral breast cancer and death from any cause). | 3 years | 
| Objective response rate | Clinical and radiological ORRs | 6 months | 
| Adverse events | All grade and high grade adverse events rate in both arms | 6 months | 
| Ovarian failure rate | Ovarian failure rates at 2 years in both groups (defined as the absence of menses in the preceding 6 months and levels of follicle-stimulating hormone (FSH) in the postmenopausal range). | 2 years |