Assessing the Efficacy and Safety of Optimal Neoadjuvant to Adjuvant Anti-HER2- Based Therapy in Nigerian Women With HER2+ Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 74
- 试验地点
- 6
- 主要终点
- Pathological Complete Response
研究概览
简要总结
Doctors leading this study would like to learn about providing cancer treatment/therapies to Nigerian women with breast cancer based on their human epidermal growth factor receptor 2 (HER2) status. This study will focus on the efficacy and safety of anti-HER2 cancer treatment before and after surgery.
详细描述
Doctors leading this study would like to learn about providing cancer treatment/therapies to Nigerian women with breast cancer based on their human epidermal growth factor receptor 2 (HER2) status. This study will focus on the efficacy and safety of anti-HER2 cancer treatment before and after surgery. Participants with HER2-positive breast cancer will receive a combination of trastuzumab with pertuzumab (PHESGO) plus chemotherapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Written informed consent must be obtained prior to any screening procedures
- •Women ages of 18 to 70 years old
- •Biopsy-accessible breast tumor of significant size for core needle biopsy /ultrasound measurable (≥ 2cm)
- •Measurable breast tumour using ultrasonography (≥ 2cm)
- •Patients with histologically confirmed carcinoma of the female breast with positive HER2 status
- •Clinical stages 2A -3C. (AJCC 2009)
- •Chemotherapy-naïve patients (for this malignancy)
- •Performance status: Eastern Cooperative Oncology Group performance status 0-3
- •Non-pregnant and not nursing. Women of childbearing potential must take the pregnancy test and must commit to receive hormone therapy with 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/mL
- •Platelet count ≥ 100,000/mL
- •Absolute neutrophil count ≥ l500/mL
- •Hemoglobin 10g/dL
- •Bilirubin ≤ 1.5 x upper limit of normal
- •serum glutamic-oxaloacetic transaminase (SGOT) and Serum glutamic pyruvic transaminase (SGPT) < 2.5 x upper limit of normal for patients without liver metastases
- •Creatinine within institutional normal limits or glomerular filtration rate ≥ 30 mL/min/1.73 m2 by Chronic Kidney Disease Epidemiology Collaboration equation (see http://mdrd.com/ for calculator)
- •Echocardiogram: Baseline left ventricular ejection fraction of ≥ 55%
排除标准
- •Patients eligible for this study must not meet any of the following criteria:
- •Pregnant or lactating women. Women of childbearing potential not using a reliable and appropriate contraceptive method. Postmenopausal women must have been amenorrhoeic for at least 12 months to be considered of non-childbearing potential. Patients will agree to continue the use of acceptable form of contraception for 7 months from the date of last drug administration (Herceptin).
- •Patients with distant metastasis
- •Serious, uncontrolled, concurrent infection(s).
- •Patients who have received more than 4 weeks of tamoxifen therapy for this malignancy. Patient who have received tamoxifen or raloxifene for purposes of chemoprevention (e.g. Breast Cancer Prevention Trial or for other past indications (including previous breast cancer) are eligible. Tamoxifen or raloxifene therapy will be discontinued at least one month before the patient is enrolled on this study.
- •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.
- •Unwillingness to participate or inability to comply with the protocol for the duration of the study
- •Patients with human epidermal growth factor receptor 2 (HER2-negative) disease
- •History of documented heart failure or systolic dysfunction (LVEF < 50%), High-risk uncontrolled arrhythmias ie, atrial tachycardia with a heart rate > 100/min at rest, significant ventricular arrhythmia (ventricular tachycardia) or higher-grade Atrioventricular (AV)-block (second degree AV-block Type 2 [Mobitz 2] or third degree AV-block),
- •Angina pectoris requiring anti-anginal medication,
- •Clinically significant valvular heart disease
- •Poorly controlled hypertension (eg, systolic > 180 mm Hg or diastolic > 100 mm Hg)
研究组 & 干预措施
Phase 1: All Participants
All participants will receive a combination of:
- docetaxel (starting dose - 75 mg/m2), increasing to 100mg/m2 by cycle 2 (if tolerated) for 4-6 cycles (for a total of 18 weeks). Docetaxel will be give as an injection.
- trastuzumab and pertuzumab (loading dose of 1200 mg of pertuzumab and 600 mg trastuzumab) for 52 weeks followed by 600 mg pertuzumab and 600 mg trastuzumab every 3 weeks for 15 cycles (for a total of 52 weeks). These two drugs will be given as subcutaneous injections under the skin.
干预措施: Trastuzumab emtansine (Drug)
Phase 1: All Participants
All participants will receive a combination of:
- docetaxel (starting dose - 75 mg/m2), increasing to 100mg/m2 by cycle 2 (if tolerated) for 4-6 cycles (for a total of 18 weeks). Docetaxel will be give as an injection.
- trastuzumab and pertuzumab (loading dose of 1200 mg of pertuzumab and 600 mg trastuzumab) for 52 weeks followed by 600 mg pertuzumab and 600 mg trastuzumab every 3 weeks for 15 cycles (for a total of 52 weeks). These two drugs will be given as subcutaneous injections under the skin.
干预措施: Pertuzumab Injection (Drug)
Phase 1: All Participants
All participants will receive a combination of:
- docetaxel (starting dose - 75 mg/m2), increasing to 100mg/m2 by cycle 2 (if tolerated) for 4-6 cycles (for a total of 18 weeks). Docetaxel will be give as an injection.
- trastuzumab and pertuzumab (loading dose of 1200 mg of pertuzumab and 600 mg trastuzumab) for 52 weeks followed by 600 mg pertuzumab and 600 mg trastuzumab every 3 weeks for 15 cycles (for a total of 52 weeks). These two drugs will be given as subcutaneous injections under the skin.
干预措施: Docetaxel (Drug)
Phase 2 - Operable (participants who are able to have surgery)
Participants in this group will have breast cancer that shows a complete or incomplete response (as assessed by ultrasound) to the study drug combination given in phase 1 of study. Based on how their breast cancer responds to the phase 1 study drugs, participants in this group will:
- undergo surgery and will continue to receive pertuzumab (600 mg) and trastuzumab (600 mg) for 36 weeks. Participants may also receive hormone therapy (as recommended by study doctor) based on status of breast cancer. This drug will be given as an injection under the skin.
Some participants in this group may also receive tamoxifen (as an oral tablet; 20 mg daily for 10 years after surgery), letrozole (as an oral tablet 2.5 mg daily for 10 years after surgery) and/or goserelin (hormone injection 10.8 mg every 1-3 months) based on their human epidermal growth factor receptor 2 (HER2) status as assessed by the treating doctor.
干预措施: Trastuzumab emtansine (Drug)
Phase 2 - Operable (participants who are able to have surgery)
Participants in this group will have breast cancer that shows a complete or incomplete response (as assessed by ultrasound) to the study drug combination given in phase 1 of study. Based on how their breast cancer responds to the phase 1 study drugs, participants in this group will:
- undergo surgery and will continue to receive pertuzumab (600 mg) and trastuzumab (600 mg) for 36 weeks. Participants may also receive hormone therapy (as recommended by study doctor) based on status of breast cancer. This drug will be given as an injection under the skin.
Some participants in this group may also receive tamoxifen (as an oral tablet; 20 mg daily for 10 years after surgery), letrozole (as an oral tablet 2.5 mg daily for 10 years after surgery) and/or goserelin (hormone injection 10.8 mg every 1-3 months) based on their human epidermal growth factor receptor 2 (HER2) status as assessed by the treating doctor.
干预措施: Goserelin (Drug)
Phase 2 - Operable (participants who are able to have surgery)
Participants in this group will have breast cancer that shows a complete or incomplete response (as assessed by ultrasound) to the study drug combination given in phase 1 of study. Based on how their breast cancer responds to the phase 1 study drugs, participants in this group will:
- undergo surgery and will continue to receive pertuzumab (600 mg) and trastuzumab (600 mg) for 36 weeks. Participants may also receive hormone therapy (as recommended by study doctor) based on status of breast cancer. This drug will be given as an injection under the skin.
Some participants in this group may also receive tamoxifen (as an oral tablet; 20 mg daily for 10 years after surgery), letrozole (as an oral tablet 2.5 mg daily for 10 years after surgery) and/or goserelin (hormone injection 10.8 mg every 1-3 months) based on their human epidermal growth factor receptor 2 (HER2) status as assessed by the treating doctor.
干预措施: Pertuzumab Injection (Drug)
Phase 2 - Operable (participants who are able to have surgery)
Participants in this group will have breast cancer that shows a complete or incomplete response (as assessed by ultrasound) to the study drug combination given in phase 1 of study. Based on how their breast cancer responds to the phase 1 study drugs, participants in this group will:
- undergo surgery and will continue to receive pertuzumab (600 mg) and trastuzumab (600 mg) for 36 weeks. Participants may also receive hormone therapy (as recommended by study doctor) based on status of breast cancer. This drug will be given as an injection under the skin.
Some participants in this group may also receive tamoxifen (as an oral tablet; 20 mg daily for 10 years after surgery), letrozole (as an oral tablet 2.5 mg daily for 10 years after surgery) and/or goserelin (hormone injection 10.8 mg every 1-3 months) based on their human epidermal growth factor receptor 2 (HER2) status as assessed by the treating doctor.
干预措施: Docetaxel (Drug)
Phase 2 - Operable (participants who are able to have surgery)
Participants in this group will have breast cancer that shows a complete or incomplete response (as assessed by ultrasound) to the study drug combination given in phase 1 of study. Based on how their breast cancer responds to the phase 1 study drugs, participants in this group will:
- undergo surgery and will continue to receive pertuzumab (600 mg) and trastuzumab (600 mg) for 36 weeks. Participants may also receive hormone therapy (as recommended by study doctor) based on status of breast cancer. This drug will be given as an injection under the skin.
Some participants in this group may also receive tamoxifen (as an oral tablet; 20 mg daily for 10 years after surgery), letrozole (as an oral tablet 2.5 mg daily for 10 years after surgery) and/or goserelin (hormone injection 10.8 mg every 1-3 months) based on their human epidermal growth factor receptor 2 (HER2) status as assessed by the treating doctor.
干预措施: Tamoxifen (Drug)
Phase 2 - Operable (participants who are able to have surgery)
Participants in this group will have breast cancer that shows a complete or incomplete response (as assessed by ultrasound) to the study drug combination given in phase 1 of study. Based on how their breast cancer responds to the phase 1 study drugs, participants in this group will:
- undergo surgery and will continue to receive pertuzumab (600 mg) and trastuzumab (600 mg) for 36 weeks. Participants may also receive hormone therapy (as recommended by study doctor) based on status of breast cancer. This drug will be given as an injection under the skin.
Some participants in this group may also receive tamoxifen (as an oral tablet; 20 mg daily for 10 years after surgery), letrozole (as an oral tablet 2.5 mg daily for 10 years after surgery) and/or goserelin (hormone injection 10.8 mg every 1-3 months) based on their human epidermal growth factor receptor 2 (HER2) status as assessed by the treating doctor.
干预措施: Letrozole (Drug)
Phase 2 - Inoperable (participants who are not able to have surgery)
Participants in this group will have breast cancer that shows a partial response (as assessed by ultrasound) to the study drugs given in phase 1 or their breast cancer stayed the same or got worse after receiving study drugs during phase 1. Based on how their breast cancer responds to the phase 1 study drug regimen, participants in this group will receive trastuzumab emtansine (intravenously) plus standard chemotherapy as recommended by their doctor.
干预措施: Trastuzumab emtansine (Drug)
结局指标
主要结局
Pathological Complete Response
时间窗: 10 years
Pathological complete response of giving three-weekly docetaxel + subcutaneous trastuzumab and Pertuzumab with Tamoxifen/Letrozole added ) to Nigerian women with Human epidermal growth factor receptor 2 (HER2-positive) breast cancer as assessed by the absence of invasive neoplastic cells at microscopic examination of the primary tumor and lymph nodes at surgery.
次要结局
- Reported Adverse Events and clinical/medical records of participants(10 years)
- Percentage of participants who are suitable for breast-conserving surgery(10 years)
- Event-free survival duration reported among participants(10 years)
- Quality of life reported among study participants(10 years)
- Genetic and epigenetic factors associated with breast cancer in Nigeria(10 years)