Carboplatin in EARLY Triple Negative Breast Cancer Trial (PEARLY Trial)

Breast Cancer Clinical 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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02441933
• Other study ID #: 4-2015-0074
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: September 1, 2015
• Est. completion date: June 30, 2025

Study information

• Verified date: May 2024
• Source: Yonsei University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 878
• Est. completion date: June 30, 2025
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 19 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Triple Negative Breast Neoplasms

Intervention

Drug:
• taxane plus carboplatin
Doxorubicin (60 mg/m2) IV + cyclophosphamide (600 mg/m2) IV every 3 weeks for 4 cycles followed by taxane plus carboplatin for 4 cycles The taxane plus carboplatin regimen can be selected based on the investigator's discretion from among the following two regimens. Docetaxel (75 mg/m2) IV plus carboplatin (AUC 5) IV every 3 weeks for 4 cycles Paclitaxel (80 mg/m2) IV weekly for 12 doses plus carboplatin (AUC 5) IV every 3 weeks for 4 cycles
• Taxane
Doxorubicin (60 mg/m2) IV + cyclophosphamide (600 mg/m2) IV every 3 weeks for 4 cycles followed by taxane for 4 cycles The taxane regimen can be selected at the investigator's discretion from among the following two regimens. Docetaxel (75 mg/m2) IV every 3 weeks for 4 cycles Paclitaxel (80 mg/m2) IV weekly for 12 doses

Locations

Country	Name	City	State
Korea, Republic of	Inje University Haeundae Paik Hospital	Busan
Korea, Republic of	Soonchunhyang university Cheonan hospital	Cheonan	Gyungkido
Korea, Republic of	Chungbuk university hospital	Cheonju	Chungchung Do
Korea, Republic of	Keimyung University Dongsan Medical Center	Daegu
Korea, Republic of	National Cancer Center	Goyang	Gyeonggido
Korea, Republic of	National Health Insurance Service Ilsan Hospital	Ilsan	Gyeonggido
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Bundang Cha Hospital	Seongnam	Gyeonggido
Korea, Republic of	Seoul national university Bundang Hospital	Seongnam
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Boramae Medical Center	Seoul
Korea, Republic of	Catholic university of Korea, Seoul St. Mary's Hospital	Seoul
Korea, Republic of	Chung Ang University Heaelthcare System	Seoul
Korea, Republic of	Gangnam Severance hospital	Seoul
Korea, Republic of	Korea University Anam hospital	Seoul
Korea, Republic of	Kyunghee University Healthcare System	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Yonsei Cancer Center at Yonsei University Medical Center	Seoul
Korea, Republic of	Ajou universwity Medical Center	Suwon	Gyeonggido
Korea, Republic of	Ulsan University Hospital	Ulsan
Korea, Republic of	Wonju Severance Christian Hospital	Wonju

Sponsors (1)

Lead Sponsor	Collaborator
Yonsei University

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	5-year event-free survival (EFS)	time from Cycle1 Day1 to the occurrence of the following events; : loco-regional recurrence, distant recurrence, death from any cause, contralateral invasive breast cancer, second primary cancer, and cancer after surgery (not R0 resection), definitive disease progression during neoadjuvant chemotherapy, inoperable status after neoadjuvant chemotherapy	5 year
Secondary	overall survival	Time from C1D1 until death from any cause	5 year
Secondary	Distant recurrence free survival	Time from C1D1 until distant recurrence	5 year
Secondary	loco-regional recurrence free survival	Time from C1D1 until locoregional recurrence	5 year
Secondary	pathologic complete response rate	no evidence of invasive carcinoma in both breast and axillary lymph nodes, regardless of ductal carcinoma in situ (ypT0isN0)	5 year