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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group A | Experimental | 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. |
|
| Group B | No Intervention | 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Goserelin | Drug | Goserelin is Luteinizing hormone releasing hormone (LHRH) analogue. |
|
| 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 |
| 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). |
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Inclusion Criteria:
Exclusion Criteria:
self-representation of gender identity
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Kyrillus S Shohdy, MD | Contact | 02 01229961016 | shohdyks@residents.kasralainy.edu.eg | |
| Loay Kassem, MD | Contact | 02 01003022907 | loay.kassem@cairocure.com |
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| ID | Term |
|---|---|
| D064726 | Triple Negative Breast Neoplasms |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
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| ID | Term |
|---|---|
| D017273 | Goserelin |
| ID | Term |
|---|---|
| D007987 | Gonadotropin-Releasing Hormone |
| D010906 | Pituitary Hormone-Releasing Hormones |
| D007028 | Hypothalamic Hormones |
| D036361 | Peptide Hormones |
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| 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 |
| D012871 |
| Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D009479 | Neuropeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D009842 | Oligopeptides |
| D009419 | Nerve Tissue Proteins |
| D011506 | Proteins |