Breast Cancer Triple Negative
Conditions
Brief summary
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
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.
Interventions
DRUGGoserelin
Goserelin is Luteinizing hormone releasing hormone (LHRH) analogue.
Sponsors
Kasr El Aini Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. Premenopausal women between 18 and 60 years. 2. Histologically proven, newly diagnosed invasive carcinoma of breast. 3. Tumors must be ER, PgR negative and HER2-neu negative. 4. Stage II or III breast cancer that is indicated for neoadjuvant systemic chemotherapy.
Exclusion criteria
1. pregnant females at time of diagnosis of breast cancer. 2. bilateral breast cancer. 3. already received treatment for breast cancer including surgery, radiation, cytotoxic, or endocrine therapy 4. history or concomitant diagnosis of another primary malignancy. 5. concurrent treatment with oral contraceptives or hormone replacement therapy (OCPs or HRT must be stopped at least 4 weeks prior to randomization).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| pathologic complete response rate | 6 months | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| LHRH-positive and/or AR-positive Rate | 6 months | Incidence of LHRH-positive and/or AR-positive cases among TNBC |
| Relapse-free Survival | 3 years | 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). |
| Objective response rate | 6 months | Clinical and radiological ORRs |
| Adverse events | 6 months | All grade and high grade adverse events rate in both arms |
| Ovarian failure rate | 2 years | 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). |
Contacts
Primary ContactKyrillus S Shohdy, MD
Backup ContactLoay Kassem, MD
Outcome results
None listed