Breast Cancer, Breast Cancer Female, Breast Cancer Stage II, Breast Cancer Stage III, HER2-positive Breast Cancer
Conditions
Keywords
breast cancer, breast cancer stage II, Breast Cancer Stage III, Docetaxel, Herceptin, neoadjuvant treatment, nigeria
Brief summary
This is a one stage phase II study with a single arm design. It will be conducted in HER-2 positive breast cancer patients in Nigeria who are chemotherapy/hormonal treatment naive.
Interventions
DRUGHerceptin
Administered for 18 cycles every three weeks (52 weeks) for each patient starting at the first day of treatment with docetaxel.
DRUGDocetaxel
Administered to all patients for a minimum of 4 cycles for 12 weeks.
DRUGFEC
Only administered to patients who received docetaxel and herceptin and were assessed as having poor response (defined as stable disease or progressive disease or partial response inoperable).
DRUGTamoxifen
Only administered to hormone-receptor positive patients. Patients will receive tamoxifen or letrozole.
DRUGLetrozole
Only administered to hormone-receptor positive patients. Patients will receive tamoxifen or letrozole.
DRUGLHRH agonist
Administered to all premenopausal patients.
Sponsors
University of Chicago
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Women ages of 18 to 70 years old 2. Biopsy-accessible breast tumor of significant size for core needle biopsy/ultrasound measurable (≥ 2cm) 3. Patients with histologically confirmed carcinoma of the female breast with 3+ positive HER2 status by IHC 4. Clinical stages IIA -IIIC (AJCC 2009) 5. Chemotherapy-naïve patients (for this malignancy) 6. Performance status: ECOG performance status 0-1 (Appendix A) 7. Non-pregnant and not nursing. Women of childbearing potential must take the pregnancy test and must commit to receive LHRH agonist Zoladex (goserelin) for two years starting from the commencement of the study medications 8. Required Initial Laboratory Data. Adequate hematologic, renal and hepatic function, as defined by each of the following: 1\. Granulocyte ≥ 1,500/μL 2. Platelet count ≥ 100,000/μL 3. Absolute neutrophil count (ANC) ≥ l500/μL 4. Hemoglobin ≥ 10g/dL 5. Bilirubin ≤ 1.5 x upper limit of normal 6. SGOT and SGPT \< 2.5 x upper limit of normal 7. Creatinine within institutional normal limits or glomerular filtration rate ≥ 30 mL/min/1.73 m2 by CKD EPI equation (see http://mdrd.com/ for calculator) 9\. ECHO: Baseline left ventricular ejection fraction of ≥ 55%
Exclusion criteria
1. 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. 2. Patients with distant metastasis (brain and/or visceral metastasis) 3. Serious, uncontrolled, concurrent infection(s). 4. Treatment for other carcinomas within the last 5 years, except non-melanoma skin cancer and treated cervical carcinoma in-situ (CCIS) 5. Participation in any investigational drug study within 4 weeks preceding the start of study treatment 6. 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. 7. Patients with HER2-negative disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Complete Pathologic Response (pCR) | 4-6 months | Pathological complete response in the breast is defined as the absence of invasive cells at microscopic examination of the primary tumor and lymph nodes at surgery. Any remaining in-situ lesions are permissible. Participants with invalid/missing pCR assessments will be defined as non-responders. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | 4-6 months | Incidence and severity of adverse drug reactions (AE) and serious adverse drug reactions (SAE) including clinical laboratory values, vital signs, ECGs and dose interruptions. |
| Progression-free Survival (PFS) | From start date of therapy to the date of first documented disease progression or death from any cause, whichever may come first, assessed up to 10 years | Time from enrollment to disease recurrence or death from any cause. |
| Duration of Response (DOR) | Up to 10 years | Time from pathological complete response to disease recurrence or death |
| Analysis of Changes From Baseline Using the Quality of Life (QoL) Instrument: EORTC. Overall Health From Baseline to End of Neoadjuvant Therapy. | From start date of therapy to end of neoadjuvant therapy approximately 4 - 6 months from commencement of chemotherapy | Global health status from EORTC QLQ-C30 instrument. Overall health rating on a scale from 1 (very poor) to 7 (excellent). Higher scores indicate better outcome. Values represent changes from baseline with positive values indicating improvement and negative values indicating worsening. |
| Analysis of Changes From Baseline Using the Quality of Life (QoL) Instrument: EORTC. Overall Quality of Life From Baseline to End of Neoadjuvant Therapy. | From start date of therapy to end of neoadjuvant therapy approximately 4 - 6 months from commencement of chemotherapy | Global quality of life status from EORTC QLQ-C30 instrument. Overall quality of life rating on a scale from 1 (very poor) to 7 (excellent). Higher scores indicate better outcome. Values represent changes from baseline with positive values indicating improvement and negative values indicating worsening. |
| Analysis of Changes From Baseline Using the Quality of Life (QoL) Instrument: EORTC. Overall Health From Baseline to 6 Months Post-therapy. | From start date of therapy to 6 months post-therapy | Global health status from EORTC QLQ-C30 instrument. Overall health rating on a scale from 1 (very poor) to 7 (excellent). Higher scores indicate better outcome. Values represent changes from baseline with positive values indicating improvement and negative values indicating worsening. |
| Analysis of Changes From Baseline Using the Quality of Life (QoL) Instrument: EORTC. Overall Quality of Life From Baseline to 6 Months Post-therapy. | From start date of therapy to 6 months post-therapy | Global quality of life status from EORTC QLQ-C30 instrument. Overall quality of life rating on a scale from 1 (very poor) to 7 (excellent). Higher scores indicate better outcome. Values represent changes from baseline with positive values indicating improvement and negative values indicating worsening. |
| Analysis of Changes From Baseline Using the Quality of Life (QoL) Instrument: EORTC | From start date of therapy to the date of first documented disease progression or death from any cause, whichever may come first, assessed up to 10 years | The various domains of QoL over time and the changes from baseline using the validated (by the European Organization for Research and Treatment of Cancer (EORTC)) QoL instrument (global and breast module). |
| Blood Concentrations of Herceptin SC Given in Combination With Docetaxel | 21 days | Blood concentrations of Herceptin SC at multiple time points using the peak exposure |
| Drug Plasma Concentration of Herceptin SC Given in Combination With FEC | 21 days | Determine the pharmacokinetic profile of Herceptin SC given in combination with FEC following poor response to TH |
| The Cardiac Toxicity Associated With TscH With FEC +scH in Breast Cancer Patients | Through study completion an average of two years | The percentage of participants with Heart failure (NYHA Class III or IV or as confirmed by a cardiologist) or a decrease in LVEF of at least 10 EF points from baseline and to below 50%. |
| The Cardiac Toxicity Associated With TscH Without FEC +scH in Breast Cancer Patients | Through study completion an average of two years | The percentage of participants with Heart failure (NYHA Class III or IV or as confirmed by a cardiologist) and a decrease in LVEF of at least 10 EF points from baseline and to below 50%. |
Countries
Nigeria
Contacts
PRINCIPAL_INVESTIGATOROlufunmilayo I Olopade, MD
University of Chicago
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 47.6 years |
| Race/Ethnicity, Customized African/Ibo | 9 Participants |
| Race/Ethnicity, Customized African/Other | 6 Participants |
| Race/Ethnicity, Customized African/Yoruba | 32 Participants |
| Region of Enrollment Nigeria | 47 participants |
| Sex: Female, Male Female | 47 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 47 |
| other Total, other adverse events | 47 / 47 |
| serious Total, serious adverse events | 7 / 47 |
Outcome results
None listed