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Docetaxel and Trastuzumab before Surgery for the Treatment of HER2-Positive Stage II-III Breast Cancer in Nigerian Women, the ARETTA Trial

Trial Status: Active

This phase II trial studies the effect of docetaxel and trastuzumab before surgery in treating HER2 positive stage II-III breast cancer in Nigerian women. Chemotherapy drugs, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Trastuzumab is a form of targeted therapy because it attaches itself to specific molecules (receptors) on the surface of cancer cells, known as HER2 receptors. When trastuzumab attaches to HER2 receptors, the signals that tell the cells to grow are blocked and the cancer cell may be marked for destruction by the body's immune system. This study is being done to determine how effective and safe docetaxel and trastuzumab are before surgery in Nigerian women with breast cancer.

Inclusion Criteria

  • Ages of 18 to 70 years old
  • Biopsy-accessible breast tumor of significant size for core needle biopsy/ultrasound measurable (>= 2 cm)
  • Patients with histologically confirmed carcinoma of the female breast with 3+ positive HER2 status by immunohistochemistry (IHC)
  • Clinical stages IIA –IIIC (American Joint Committee on Cancer [AJCC] 2009)
  • Chemotherapy-naïve patients (for this malignancy)
  • Eastern Cooperative Oncology Group (ECOG) performance status 0−1
  • Non-pregnant and not nursing. Women of childbearing potential must take the pregnancy test and must commit to receive luteinizing hormone-releasing hormone (LHRH) agonist Zoladex (goserelin) for two years starting from the commencement of the study medications
  • Granulocyte >= 1,500/uL
  • Platelet count >= 100,000/uL
  • Absolute neutrophil count (ANC) >= l500/uL
  • Hemoglobin >= 10 g/dL
  • Bilirubin =< 1.5 x upper limit of normal
  • Serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) < 2.5 x upper limit of normal
  • Creatinine within institutional normal limits or glomerular filtration rate >= 30 mL/min/1.73 m^2 by Chronic Kidney Disease (CKD)-Epidemiology (EPI) equation
  • Echocardiography (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, human immunodeficiency virus (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

Illinois

Chicago
University of Chicago Comprehensive Cancer Center
Status: ACTIVE
Contact: Olufunmilayo Falusi Olopade
Phone: 773-702-1632

Nigeria

Ibadan
University College Hospital
Status: ACTIVE
Contact: Atara Ntekim
Phone: 234808023059292
Idi-Araba
Lagos University Teaching Hospital
Status: ACTIVE
Contact: Anthonia Sowunmi
Phone: 2348037216723
Ife
Obafemi Awolowo University Teaching Hospital
Status: ACTIVE
Contact: Olukayode A. Arowolo
Phone: 2348037171477
Ikeja
Lagos State University Teaching Hospital
Status: ACTIVE
Contact: Abiodun O. Popoola
Phone: 234-8033021434

PRIMARY OBJECTIVES:

I. To determine the efficacy of docetaxel + trastuzumab (Herceptin) subcutaneous (SC) every three weeks for four cycles with or without fluorouracil, epirubicin, and cyclophosphamide (FEC) + Herceptin SC for three cycles (with tamoxifen/letrozole added to estrogen receptor [ER]/progesterone receptor [PR] Positive patients) in Nigerian women with HER2-positive breast cancer.

II. To determine the toxicity of every three-weeks docetaxel + SC Herceptin with or without FEC + Herceptin SC for three cycles (with tamoxifen/letrozole added to ER/PR Positive patients) in Nigerian women with HER2- positive breast cancer.

SECONDARY OBJECTIVES:

I. To evaluate other response-related endpoints: duration of response (DOR), clinical response, progressive disease during neoadjuvant treatment, breast-conserving surgery, invasive disease-free survival.

II. To determine the cardiac toxicity associated with SC Herceptin (TscH) with or without FEC +scH in breast cancer patients.

III. To determine the pharmacokinetic profile of Herceptin SC given in combination with docetaxel.

IV. To determine the pharmacokinetic profile of Herceptin SC given in combination with FEC following poor response to trastuzumab (TH).

V. To evaluate the quality of life (QoL) of patients on every three-weeks docetaxel (+ FEC) with Herceptin over time.

VI. To explore mechanisms of resistance to HER2 targeted therapy in Nigerian women.

OUTLINE:

Patients receive trastuzumab subcutaneously (SC) over 2-5 minutes on day 1. Treatment with trastuzumab repeats every 21 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity. Pre-menopausal and hormone receptor positive patients also receive goserelin acetate SC every 3 months for 2 years in the absence of disease progression or unacceptable toxicity. Patients also receive docetaxel intravenously (IV) over 1 hour on day 1. Treatment docetaxel repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Within 4 weeks of completion of docetaxel, patients with complete clinical response (CCR) undergo surgery. Patients with partial response or stable disease receive fluorouracil IV, epirubicin IV over 1 hour, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. After completion of surgery, hormone receptors positive patients also receive tamoxifen orally (PO) daily or letrozole PO daily for 10 years in the absence of disease of progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 and 60 days, every 3 months for 2 years, and then every 6 months for up to 10 years.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
University of Chicago Comprehensive Cancer Center

Principal Investigator
Olufunmilayo Falusi Olopade

  • Primary ID IRB18-1178
  • Secondary IDs NCI-2020-13973
  • Clinicaltrials.gov ID NCT03879577