Adjuvant Platinum and Taxane in Triple-negative Breast Cancer (PATTERN)

Triple Negative Breast Cancer Clinical Trial

Official title:

A Prospective， Randomized， Open-label， Multicentric，phaseIII Clinical Trial Compared With PC and CEF100 Followed by Docetaxel as Adjuvant Chemotherapy Regimen for Chinese Primary Triple Negative Breast Cancer Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01216111
• Other study ID #: Fudan TNBC Adjuvant CT
• Status: Completed
• Phase: Phase 3
• Start date: January 1, 2011
• Est. completion date: April 20, 2016

Study information

• Verified date: May 2020
• Source: Fudan University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Previous studies in Western country show that triple-negative breast cancer has aggressive clinical and pathological features compared with non-triple negative breast cancer, including onset at a young age, advanced clinical stage, high histologic and nuclear grade and more distant recurrence.

According to the characteristics of triple negative breast tumor, the TNBC patients can benefit neither from hormonal therapies nor from target therapies against Her2 receptors. The only systemic therapy currently available is chemotherapy, and prognosis remains poor. It becomes more and more important to investigate the sensitive chemotherapy regimen for triple negative patients.

Cisplatin-based regimen was active for the patients of lung cancer, colorectal cancer and ect. Triple negative breast cancer patients were more sensitive to platinum-based chemotherapy regimens according to the results of some retrospective studies.

The investigators hypothesized that paclitaxel combined with cisplatin is more sensitive to triple negative breast cancer compared with CEF followed by docetaxel.

Description:

Eligibility Female adults(18-70 years old) are eligible if they had histologically confirmed primary breast cancer. Patients also had Eastern Cooperative Oncology Group(ECOG) Performance status of 0 or 1, absolute neutrophil count (ANC)>1500/mm3,hemoglobin >90g/dL, and platelet count >100,000/mm3,creatinine<2.5 times the upper limit of normal(ULN)）, transaminases<3 times ULN or alkaline phosphatase<4 times ULN if transaminases was normal, and total bilirubin <1.5 times ULN. Exclusion criteria were active infection, pregnancy, other primary malignancy (except in situ carcinoma of cervix or adequately treated nonmelanomatous carcinoma of the skin), any documented distant metastasis and uncontrolled systemic diseases.

This study protocol was approved by institutional ethic review boards and conducted according to guidelines for good clinical practice and the Helsinki Declaration.All patients provided written informed consent.

Outcome Measures Primary Endpoint：5 year Disease Free Survival（DFS） Second Endpoints：5 year distant disease free survival （DDFS） 5 year event free survival （EFS） 5 year overall survival （OS） 5 year DFS in gBRCA1 mutation carriers and homologous recombination repair (HRR)-related gene mutation carriers

Recruitment information / eligibility

• Status: Completed
• Enrollment: 647
• Est. completion date: April 20, 2016
• Est. primary completion date: April 20, 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Women aged from 18 to 70 years;

2. Histologically proven invasive unilateral breast cancer (regardless of the type);

3. Initial clinical condition compatible with complete initial resection;

4. No residual macro or microscopic tumor after surgical excision;

5. Beginning of chemotherapeutic treatment no later than day 42 after the initial surgery;

6. positive lymph node or negative lymph node with tumor size > 1.0cm

7. Patient presenting one of the following criteria (reviewed before randomization by referent pathologist):

Triple negative (ER-PR-Her-2-) Hormone receptor negativity is defined as ER<1%, PR<1% (IHC), HER2 negativity is defined as IHC 0-1+, or [IHC 2+ and FISH or CISH negative].

8. No clinically or radiologically detectable metastases (M0);

9. No peripheral neuropathy > 1;

10. WHO Performance status (ECOG) of 0 or 1;

11. Adequate recovery from recent surgery (at least one week must have elapsed from the time of a minor surgery (excluding breast biopsy); at least three weeks for major surgery);

12. Adequate hematological function (neutrophil count ³ 2x109/l, platelet count ³ 100x 109/l, Hemoglobin > 9 g/dl);

13. Adequate hepatic function: ASAT and ALAT = 3 ULN alkaline phosphatases = 2.5 ULN,total bilirubin = 1,5 ULN;

14. Adequate renal function: serum creatinine = 1 ULN;

15. Patients accepting contraception intake during the overall length of treatment if of childbearing potential;

16. Adequate cardiac function, LEVF value > 50% by Muga scan or echocardiography;

17. Signed written informed consent.

Exclusion Criteria:

1. Bilateral breast cancer or patient with controlateral DCIS;

2. Any metastatic impairment, including homolateral sub-clavicular node involvement,regardless of its type;

3. Any T4 lesion (UICC1987) (cutaneous invasion, deep adherence, inflammatory breast cancer);

4. ER+ or PR+ or Her-2 overexpression

5. Any clinically or radiologically suspect and non-explored damage to the controlateral breast;

6. Any chemotherapy, hormonal therapy or radiotherapy before surgery;

7. Previous cancer (excepted cutaneous baso-cellular epithelioma or uterin peripheral ephitelioma) in the preceding 5 years, including invasive controlateral breast cancer;

8. Patients already included in another therapeutic trial involving an experimental drug;

9. Patients with other concurrent severe and/or uncontrolled medical disease or infection which could compromise participation in the study;

10. LEVF < 50% (MUGA scan or echocardiography);

11. Clinically significant cardiovascular disease (e.g. unstable angina, congestive heart failure, uncontrolled hypertension (>150/90), myocardial infarction or cerebral vascular accidents) within 6 months prior to randomization;

12. Known prior severe hypersensitivity reactions to agents containing Cremophor EL;

13. Women of childbearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and up to 8 weeks after treatment completion;

14. Women who are pregnant or breastfeeding. Adequate birth control measures should be taken during study treatment phase;

15. Women with a positive pregnancy test en enrollment or prior to study drug administration;

16. Patients with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial;

17. Individual deprived of liberty or placed under the authority of a tutor.

Related Conditions & MeSH terms

• Breast Neoplasms
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

Drug:
• Paclitaxel Cisplatin
Paclitaxel 80 mg/m2 D1,8,15 Cisplatin AUC=2 D1,8,15 1 cycle = 28days PC*6
• fluorouracil epirubicin cyclophosphamide and docetaxel (FEC-T)
fluorouracil 500 mg/m2, epirubicin 100 mg/m2, and cyclophosphamide 500 mg/m2 intravenously on day 1 every 21 days for three cycles followed by docetaxel 100 mg/m2 intravenously

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Fudan University	Chinese Anti-Cancer Association

References & Publications (7)

Carey LA, Dees EC, Sawyer L, Gatti L, Moore DT, Collichio F, Ollila DW, Sartor CI, Graham ML, Perou CM. The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res. 2007 Apr 15;13(8):2329-34. — View Citation

Cleator S, Heller W, Coombes RC. Triple-negative breast cancer: therapeutic options. Lancet Oncol. 2007 Mar;8(3):235-44. Review. — View Citation

Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA, Lickley LA, Rawlinson E, Sun P, Narod SA. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res. 2007 Aug 1;13(15 Pt 1):4429-34. — View Citation

Hayes DF, Ethier S, Lippman ME. New guidelines for reporting of tumor marker studies in breast cancer research and treatment: REMARK. Breast Cancer Res Treat. 2006 Nov;100(2):237-8. Epub 2006 Jun 14. — View Citation

Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lønning PE, Børresen-Dale AL, Brown PO, Botstein D. Molecular portraits of human breast tumours. Nature. 2000 Aug 17;406(6797):747-52. — View Citation

Reis-Filho JS, Tutt AN. Triple negative tumours: a critical review. Histopathology. 2008 Jan;52(1):108-18. doi: 10.1111/j.1365-2559.2007.02889.x. Review. — View Citation

Yehiely F, Moyano JV, Evans JR, Nielsen TO, Cryns VL. Deconstructing the molecular portrait of basal-like breast cancer. Trends Mol Med. 2006 Nov;12(11):537-44. Epub 2006 Sep 29. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	disease-free survival	time from random assignment to first relapse (local, regional and distant), contralateral breast cancer	5 year
Secondary	distant disease-free survival	time from random assignment to distant recurrence or death	5 year
Secondary	relapse-free survival	time from the date of randomization to local, regional, distant relapse or death	5 year
Secondary	disease-free survival gBRCA1 mutation carriers and homologous recombination repair (HRR)-related gene mutation carriers		5 year
Secondary	overall survival	time from randomization until death with any cause	5 year