Paclitaxel and Carboplatin before Surgery in Treating Nigerian Women with Stage IIA-IIIC Breast Cancer
This phase II trial studies how well paclitaxel works with carboplatin before surgery in treating Nigerian women with stage IIA-IIIC breast cancer before surgery. Drugs used in chemotherapy, such as paclitaxel and carboplatin, 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.
Inclusion Criteria
- Biopsy-accessible breast tumor of significant size for core needle biopsy (>= 2cm)
- Patients with histologically confirmed carcinoma of the female breast with any or unknown hormone receptors (HRs)/HER2 status
- Clinical stages IIA –IIIC (American Joint Committee on Cancer [AJCC] 2009)
- Chemotherapy-naive patients (for this malignancy)
- Eastern Cooperative Oncology Group (ECOG) performance status 0−3
- 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) >= 1500/uL
- Hemoglobin^3 10g/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 for patients without liver metastases
- Creatinine within institutional normal limits or glomerular filtration rate >= 30 mL/min/1.73 m^2 by chronic kidney disease (CKD) epidemiology collaboration (EPI) equation
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 will agree to continue the use of acceptable form of contraception for 30 days from the date of last drug administration
- Patients with brain 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
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03058939.
PRIMARY OBJECTIVES:
I. To evaluate the anti-tumor activity of weekly paclitaxel and/or paclitaxel and carboplatin (PC) chemotherapy in Nigerian women with breast cancer.
SECONDARY OBJECTIVES:
I. To evaluate the safety profile of weekly paclitaxel and/or PC combination in breast cancer patients.
II. To determine the pattern of response to weekly paclitaxel and PC in combination with hormone therapy or with Herceptin (H)/pertuzumab (Ptz) dual anti-HER2 blockade based on status of clinical markers − hormone receptors (estrogen receptor [ER] and progesterone receptor [PgR]) and HER2, and other markers.
III. To determine the pharmacokinetic profile of trastuzumab (Herceptin subcutaneous [SC]) given in combination with Perjeta, paclitaxel and PC.
IV. To determine the pharmacokinetic profile of Perjeta given in combination with Herceptin SC, paclitaxel and paclitaxel + carboplatinum.
V. To evaluate response-related endpoints: duration of response (DOR) and progression-free survival (PFS).
VI. To evaluate the quality of life (QoL) of patients on weekly paclitaxel and weekly PC chemotherapy over time.
VII. To assess the genetic and epigenetic factors associated with breast cancer in Nigeria.
OUTLINE: Patients are assigned to 1 of 2 groups.
GROUP I (HER2+): Patients receive paclitaxel intravenously (IV) over 60 minutes every week for up to 8 courses, trastuzumab SC on day 1 every 21 days for up to 3 courses, and pertuzumab IV over 60 minutes on day 1 every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
GROUP II (HER2-): Patients receive paclitaxel IV over 60 minutes every week for up to 8 courses in the absence of disease progression or unacceptable toxicity.
Patients are assigned to 1 of 4 groups.
GROUP III (HER2+ COMPLETE/PARTIAL RESPONSE): Patients receive paclitaxel IV over 60 minutes every week for up to 8 courses, trastuzumab SC on day 1 every 21 days for up to 3 courses, and pertuzumab IV over 60 minutes on day 1 every 21 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.
GROUP IV (HER2- COMPLETE/PARTIAL RESPONSE): Patients receive paclitaxel IV over 60 minutes every week for up to 8 courses in the absence of disease progression or unacceptable toxicity.
All patients with complete/partial response undergo surgery after treatment.
GROUP V (HER2+ STABLE/PROGRESSIVE DISEASE): Patients receive paclitaxel IV over 1 hour weekly and carboplatin IV over 1 hour on days 1, 8 and 15 for up to 8 courses, trastuzumab SC on day 1 every 21 days for up to 4 courses and pertuzumab IV on day 1 every 21 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.
GROUP VI (HER2- STABLE/PROGRESSIVE DISEASE): Patients receive paclitaxel IV over 1 hour weekly and carboplatin IV over 1 hour on days 1, 8 and 15 for up to 8 courses in the absence of disease progression or unacceptable toxicity.
All patients with stable/progressive disease receive fluorouracil IV, epirubicin hydrochloride IV over 60 minutes, and cyclophosphamide IV every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients also receive trastuzumab SC every 3 weeks for up to 11 courses, tamoxifen citrate PO or letrozole PO for up to 10 years, and goserelin acetate SC every 12 weeks for up to 8 courses. Within 6-8 weeks after surgery, hormone receptor positive patients with complete or partial response receive tamoxifen citrate PO or letrozole PO every 4 weeks for up to 10 years and goserelin acetate SC every 12 weeks for up to 10 years. Within 6-8 weeks after surgery, HER2 positive patients with complete or partial response receive trastuzumab citrate SC every 3 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity
After completion of study treatment, patients are followed up every 3 months for 2 years, then every 6 months for 10 years.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationUniversity of Chicago Comprehensive Cancer Center
Principal InvestigatorOlufunmilayo Falusi Olopade
- Primary IDIRB15-1005
- Secondary IDsNCI-2017-00754
- ClinicalTrials.gov IDNCT03058939