A Phase III Trial of Carboplatin as Adjuvant Chemotherapy in Triple Negative Breast Cancer

A Phase III Trial of Carboplatin as Adjuvant Chemotherapy Versus Observation in Triple Negative Breast Cancer With Pathologic Residual Cancer After Neoadjuvant Chemotherapy: POST-Neo Adjuvant Study

This study is designed to investigate the efficacy of carboplatin, as a post-operative adjuvant chemotherapy for triple negative breast cancer patients who have pathologic residual cancer after the preoperative chemotherapy.

Study Overview

• Status: Unknown
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: carboplatin

Detailed Description

In Neo-adjuvant period Four cycles of 60 mg/m2 doxorubicin and 600 mg/m2 cyclophosphamide therapy at 3-week intervals followed by four cycles of 100 mg/m2 docetaxel at 3-week intervals.

In POST Neo-adjuvant period

Randomization:

At the time of post neo-adjuvant period, the patients will be assigned to each treatment group in a 1:1 ratio i.e. carboplatin AUC 6 group vs. observation group. Six cycles of carboplatin (AUC=6) on the first day of every 21 days.

• Study Type: Interventional
• Enrollment (Anticipated): 587
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Byeong Woo Park, MD, PhD; Phone Number: 82-2-2228-8125; Email: nobelg@yuhs.ac

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Clinical diagnosis of breast cancer

  1. Female patients

  2. Histologically confirmed invasive breast cancer

     1. Primary tumor greater than 2cm diameter, measured by mammography and sonography
     2. Any N
  3. ER (estrogen receptor)/ PR (progesterone receptor) / HER2 (negative/ negative/ negative)(ER <1%, PR<1%, IHC 0, 1+ or FISH - in case of IHC (immuno-histochemistry) 2+)
  4. No evidence of metastasis (M0)
  5. No prior hormonal, chemotherapy or radiotherapy is allowed.
  6. No breast operation other than biopsy to make diagnosis is allowed.
  7. Age: 20-years and older, not pregnant pre-, and postmenopausal women with good performance status (ECOG 0-1)
  8. Adequate hematopoietic function: Absolute granulocyte count 1500/mm3, platelet 100,000/mm3, Hemoglobin 10 g/mm3
  9. Adequate renal function: Serum creatinine 1.5 mg/dl
  10. Adequate hepatic function: total bilirubin: 1.5 mg/dl, AST(aspartate aminotransferase)/ALT (alanine transaminase): 2 times normal, Alkaline phosphatase:2 times normal
  11. Written informed consent
  12. Normal mental function to understand and sign the consent
  13. Cardiac function: normal or nonspecific EKG taken within 1 mo of enrollment.
  14. LVEF (left ventricular ejection fraction)50% by MUGA (multiple gated acquisition scan) or Echocardiogram taken within 1 mo of enrollment

Exclusion Criteria:

1. Patients who received hormonal, chemotherapy or radiotherapy for breast cancer
2. Patients who underwent surgery for breast cancer
3. Patients with a history of uncompensated congestive heart failure
4. Patients with inflammatory breast cancer (T4d)
5. Patients without primary tumor (T0)
6. Patients who have history of cancer other than in situ uterine cervix cancer or non-melanotic skin cancer
7. Known hypersensitivity to any of the study drugs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: carboplatin chemotherapy; At the time of post neo-adjuvant period, the patients will be assigned to each treatment group in a 1:1 ratio i.e. carboplatin AUC 6 group vs. observation group. Six cycles of carboplatin (AUC=6) on the first day of every 21 days.	Drug: carboplatin; carboplatin as adjuvant chemotherapy; Other Names: Adding adjuvant arm
No Intervention: Observation arm; In this observation arm, patients should be follow up with regular interval without treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free survival (DFS)	To compare DFS between carboplatin and observation within non-pCR (complete remission) patients	up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival	To compare overall survival (OS) between carboplatin and observation within non-pCR patients.	up to 5years
pCR rate	To assess the pCR rate (no residual invasive carcinoma in primary breast and axillary lymph node) within total TNBC patients.	up to 3 years
The percentage of patients who receive breast conserving surgery.	To assess the percentage of patients who receive breast conserving surgery within total triple negative breast cancer patients	up to 3years
Number of adverse events	Number of adverse events in patients with non-pCR.	up to 3years

Other Outcome Measures

Outcome Measure	Time Frame
difference in gene expression pattern	up to 5 years

Collaborators and Investigators

• Sponsor: Severance Hospital
• Investigators: Principal Investigator: Byeong Woo Park, MD, PhD, Severance Hospital

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Anticipated): March 1, 2017
• Study Completion (Anticipated): March 1, 2018

Study Registration Dates

• First Submitted: September 26, 2012
• First Submitted That Met QC Criteria: December 16, 2012
• First Posted (Estimate): December 19, 2012

Study Record Updates

• Last Update Posted (Estimate): December 25, 2012
• Last Update Submitted That Met QC Criteria: December 21, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Keywords: adjuvant chemotherapy; Triple negative breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Antineoplastic Agents; Carboplatin
• Other Study ID Numbers: Severance_BR_01; DA-TNBC (Other Grant/Funding Number: DA-TNBC)