Clinical trial NCT03304756: Study of Neoadjuvant Treatment of Locally Advanced Breast Cancer With CAP Regimen
Official title: Phase II Study of Neoadjuvant Treatment of Locally Advanced Breast Cancer Patients With the CAP Regimen
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Triple Negative Breast Cancer Patients
Keywords: locally advanced breast cancer
triple negative
cisplatin
Lead sponsor: Instituto Nacional de Cancer, Brazil
Sponsor class: OTHER_GOV
Collaborators: name: Dana-Farber Cancer Institute
First posted: 2017-10-09
Enrollment: 41
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a single arm, single center, non-randomized, phase II trial of stage IIB/III TNBC. Patients received neoadjuvant chemotherapy with cisplatin (50 mg/m2) in combination with doxorubicin (50 mg/m2) and cyclophosphamide (500 mg/m2) every 21 days and for a total of 6 cycles. After surgery, adjuvant chemotherapy consisting of docetaxel (75 mg/m2) every 21 days was further provided for 4 cycles. Primary outcome was pathological complete response in the breast and axilla (pCR; ypT0ypN0). Secondary outcomes were safety, disease-free survival and overall survival.

Detailed description: This is a non-randomized, open-label, single arm, single center, phase II clinical trial. Patients received neoadjuvant chemotherapy with cisplatin (50 mg/m2, intravenous \[IV\], day 1) in combination with doxorubicin (50 mg/m2, IV, day 1) and cyclophosphamide (500 mg/m2, IV, day 1) every 21 days and for a total of 6 cycles (CAP regimen). Subsequent mastectomy plus axillary lymph node dissection was performed. Pathological specimen was analyzed to assess tumor response in the breast and axilla. Adjuvant chemotherapy consisting of docetaxel (75 mg/m2, IV) every 21 days was further provided for 4 cycles. In case of tumor progression during neoadjuvant treatment, CAP was discontinued and additional local or systemic treatment was provided at the discretion of the investigator. The protocol was approved by the institutional review board of National Cancer Institute - Brazil. All patients provided written informed consent. The Brazilian Group of Breast Cancer Studies (GBECAM) and National Cancer Institute -Brazil were the academic sponsors and National Cancer Institute- Brazil was the funding source of the trial.

Eligibility criteria: Inclusion Criteria:

1. Female patients with locally advanced breast cancer (stages IIB, IIIA and IIIB), confirmed anatomopathologically, with hormonal receptors (Estrogen and / or progesterone) and ERBB2 negative to the immunohistochemical study pattern.
2. Presence of measurable disease according to RECIST criteria.
3. Staging with chest X-ray, abdominal ultrasound and bone scintigraphy Without evidence of metastatic disease. Capture in bone scintigraphy should be Evaluated by simple radiographs.
4. Performance Status (PS) of Eastern Cooperative Oncology Group (ECOG) ≤ 2.
5. Adequate haematological function, evidenced by higher hemoglobin level Than 9 g / dl, neutrophil count greater than 1,500 / mm 3 and platelet count greater than 100,000 / mm 3.
6. Adequate liver function, evidenced by bilirubin levels below 1.5 of normal values and liver enzyme levels less than 2.5 times normal.
7. Adequate renal function, evidenced by creatinine levels lower than 1.5 times normal value and / or estimated creatinine clearance (Cockroft) greater than 50 ml / min.
8. Preserved cardiac function assessed by Doppler echocardiography.
9. Socio-cultural ability to understand a clinical study and the need to Attend regularly for medical examinations and appointments.

Exclusion Criteria:

1. Patients with a history of previous neoplasia, except non melanoma skin cancer.
2. Previously treatment of breast cancer with surgery, chemotherapy or Hormone therapy.
3. Presence of metastatic disease
4. Concomitant malignant neoplasm (including contralateral breast).
5. Presence of uncontrolled heart, kidney or lung disease.
6. Presence of uncontrolled diabetes mellitus.
7. Pregnancy

Primary outcomes:
measure: Pathological complete response (pCR)
timeFrame: 6 months
Secondary outcomes:
measure: Safety assessed according to NCI CTCAE
timeFrame: 5 years follow-up
measure: Disease-free survival (DFS)
timeFrame: 5 years follow-up
measure: Overall survival (OS)
timeFrame: 5 years follow-up
Other outcomes:
Locations:
Study officials:
affiliation: Instituto Nacional de Cancer
name: José Bines, Doctorate
role: STUDY_CHAIR
affiliation: Medical oncologist in Boston, and affiliated with Dana-Farber Cancer Institute
name: Otto Metzger, Oncologist
role: STUDY_DIRECTOR
affiliation: Instituto Nacional de Cancer
name: José Bines, Doctorate
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ferreira AR, Metzger-Filho O, Sarmento RMB, Bines J. Neoadjuvant Treatment of Stage IIB/III Triple Negative Breast Cancer with Cyclophosphamide, Doxorubicin, and Cisplatin (CAP Regimen): A Single Arm, Single Center Phase II Study (GBECAM 2008/02). Front Oncol. 2018 Jan 24;7:329. doi: 10.3389/fonc.2017.00329. eCollection 2017.