Clinical trial NCT02441933: Carboplatin in EARLY Triple Negative Breast Cancer Trial (PEARLY Trial)
Official title: A Randomized, Multicenter, Open-label, Phase III Trial Comparing Anthracyclines Followed by Taxane Versus Anthracyclines Followed by Taxane Plus Carboplatin as (Neo) Adjuvant Therapy in Patients With Triple-negative Breast Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Breast Cancer
Lead sponsor: Yonsei University
Sponsor class: OTHER
First posted: 2015-05-12
Enrollment: 878
Sex: FEMALE
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized, open-label, multicenter, phase III study comparing anthracyclines followed by taxane to anthracyclines followed by taxane plus carboplatin as (neo)adjuvant therapy in patients with triple-negative breast cancer.

Patients with stage II/III operable triple-negative breast cancer are eligible. Patients who need adjuvant chemotherapy after breast surgery as well as patients who need neoadjuvant chemotherapy for TNBC are eligible.


Eligibility criteria: Inclusion Criteria:

1. Female patients who are \>18 years of age
2. ECOG 0 or 1
3. The tumor must be invasive carcinoma of the breast on histologic examination
4. The tumor must have been determined to be HER2-negative, as follows:

   * IHC 0 or 1+; or
   * IHC 2+ and ISH non-amplified, with a ratio of \<2.0, and if reported, an average HER2 gene copy number of \<6 signals/cell; or
   * ISH non-amplified without IHC
5. The tumor must have been determined to be ER- and PR-negative, as assessed by the current ASCO/CAP guidelines.
6. All of the following staging criteria (AJCC 7th edition) must be met:

   * Lymph node-positive disease: cytologically positive in the neoadjuvant group\* and pathologically positive in the adjuvant group
   * If the lymph node is cytologically or pathologically negative, the tumor size must be \>2.0 cm (\* In the neoadjuvant group, if there is evidence of suspicious axillary lymph nodes at the baseline imaging study or physical examination, then FNA or core biopsy is required to confirm the nodal status)
7. The patient must have undergone either a mastectomy or lumpectomy in the adjuvant group
8. The patient must have completed one of the nodal surgery procedures listed below in the adjuvant group:

   * Sentinel lymph node biopsy (SLNB) alone:

V If pathologic nodal staging based on SLNB is pN0 V If pathologic nodal staging based on SLNB is 1 or 2 positive nodes, the primary tumor must be T1 or T2 by pathologic evaluation and lumpectomy and the nodal involvement must be limited to 1 or 2 positive nodes

* SLNB followed by removal of additional non-sentinel LNs if the SLN is positive; or
* Axillary lymphadenectomy with or without SLNB (In the neoadjuvant group, if baseline LN NAB or core biopsy is positive, ALND should be performed) 9) LVEF assessment by echocardiography or MUGA scan must be \>50%, regardless of the cardiac imaging facility's lower limit of normal 10) The patient must have adequate hepatic, renal, and bone marrow function;
* Bone marrow function Hb: ≥ 10.0 g/dL ANC: ≥ 1,500/µL Platelet count: ≥ 10 × 10⁴/µL
* Renal function Creatinine: ≤ 1.5 × UNL or Creatine clearance (Ccr) \>50 ml/min by the Cockcroft formula
* Hepatic function Total Bilirubin: ≤ 1.5 × UNL AST/ALT: ≤ 2.5 × UNL 10) Ability and willingness to comply with the study visits, treatment, testing, and with the protocol, as per investigator's judgment

Exclusion Criteria:

1. Any prior systemic treatment for primary invasive breast cancer
2. cT4 or pT4 tumors including inflammatory breast cancer
3. Occult breast cancer
4. Evidence of metastatic breast cancer
5. Patients with second primary cancer; EXCEPTIONS: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, DCIS of the breast, thyroid cancer with a size of \<2 cm (papillary, follicular, and medullary type), and other solid tumors curatively treated with no evidence of disease for \>5 years prior to randomization.
6. Simultaneous bilateral breast cancer
7. Patients considered a poor medical risk due to a serious, uncontrolled medical disorder or uncontrolled infection.
8. Pregnant or breastfeeding women

Primary outcomes:
measure: 5-year event-free survival (EFS)
timeFrame: 5 year
Secondary outcomes:
measure: overall survival
timeFrame: 5 year
measure: Distant recurrence free survival
timeFrame: 5 year
measure: loco-regional recurrence free survival
timeFrame: 5 year
measure: pathologic complete response rate
timeFrame: 5 year
Other outcomes:
Locations:
city: Cheonju
country: Korea, Republic of
facility: Chungbuk university hospital
state: Chungchung Do
city: Goyang
country: Korea, Republic of
facility: National Cancer Center
state: Gyeonggido
city: Ilsan
country: Korea, Republic of
facility: National Health Insurance Service Ilsan Hospital
state: Gyeonggido
city: Seongnam
country: Korea, Republic of
facility: Bundang Cha Hospital
state: Gyeonggido
city: Suwon
country: Korea, Republic of
facility: Ajou universwity Medical Center
state: Gyeonggido
city: Cheonan
country: Korea, Republic of
facility: Soonchunhyang university Cheonan hospital
state: Gyungkido
city: Busan
country: Korea, Republic of
facility: Inje University Haeundae Paik Hospital
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Medical Center
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seongnam
country: Korea, Republic of
facility: Seoul national university Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Boramae Medical Center
city: Seoul
country: Korea, Republic of
facility: Catholic university of Korea, Seoul St. Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Chung Ang University Heaelthcare System
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam hospital
city: Seoul
country: Korea, Republic of
facility: Kyunghee University Healthcare System
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Yonsei Cancer Center at Yonsei University Medical Center
city: Ulsan
country: Korea, Republic of
facility: Ulsan University Hospital
city: Wonju
country: Korea, Republic of
facility: Wonju Severance Christian Hospital
Study officials:
References: