Clinical Trials /

Neoadjuvant Study of Two Platinum Regimens in Triple Negative Breast Cancer

NCT02413320

Description:

Evaluate if the two carboplatin containing chemotherapy regimens will reduce the growth of breast cancer cells in women with Stage I, II, or III triple negative breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Neoadjuvant Study of Two Platinum Regimens in Triple Negative Breast Cancer
  • Official Title: Randomized Open Label Phase II Trial of Neoadjuvant Carboplatin Plus Docetaxel or Carboplatin Plus Paclitaxel Followed by Doxorubicin Plus Cyclophosphamide in Stage I-III Triple-negative Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: 2015-IIT-Neoadjuvant-BRST-TNBC
  • NCT ID: NCT02413320

Conditions

  • Triple-negative Breast Cancer

Interventions

DrugSynonymsArms
PaclitaxeltaxolCarboplatin + Paclitaxel then Doxorubicin + Cyclophosphamide
CarboplatinparaplatinCarboplatin + Docetaxel
DoxorubicinadriamycinCarboplatin + Paclitaxel then Doxorubicin + Cyclophosphamide
Cyclophosphamidecytoxin, procytoxCarboplatin + Paclitaxel then Doxorubicin + Cyclophosphamide
DocetaxeltaxotereCarboplatin + Docetaxel

Purpose

Evaluate if the two carboplatin containing chemotherapy regimens will reduce the growth of breast cancer cells in women with Stage I, II, or III triple negative breast cancer.

Detailed Description

      Sporadic and germline BRCA mutation associated triple-negative breast cancer share several
      pathological and molecular similarities which have led to the exploration of DNA damaging
      agents like platinum compounds in patients with triple-negative breast cancer. Recent studies
      demonstrate that addition of neoadjuvant carboplatin to
      doxorubicin/cyclophosphamide/taxane-based chemotherapy improves pathological complete
      response in patients with stage I-III triple-negative breast cancer but also increase
      toxicity.

      A recent study reported encouraging pathological complete response rates with a
      non-anthracycline carboplatin plus docetaxel neoadjuvant chemotherapy regimen in a cohort of
      49 triple negative breast cancer patients. This chemotherapy regimen of carboplatin plus
      docetaxel yielded an overall pathological complete response rate of 65% in unselected
      triple-negative breast cancer with pathological complete response rates of 61% in sporadic
      and 77% in germline BRCA-associated triple-negative breast cancer. The chemotherapy regimen
      of carboplatin/docetaxel is well tolerated and should be studied further and compared with
      regimens that add carboplatin to the standard anthracycline/taxane containing regimens.

      This is the basis for the proposed randomized neoadjuvant phase II study to further estimate
      and compare pathological complete response rates of carboplatin plus docetaxel x 6 cycles to
      carboplatin plus paclitaxel x 4 cycles followed by doxorubicin plus cyclophosphamide x 4
      cycles in stage I-III triple negative-breast cancer.
    

Trial Arms

NameTypeDescriptionInterventions
Carboplatin + Paclitaxel then Doxorubicin + CyclophosphamideActive ComparatorPaclitaxel (80mg/m2) given IV every week x12 weeks and Carboplatin (AUC 6) given IV every 21 days x 4 cycles, followed by Doxorubicin (60mg/m2) given IV and Cyclophosphamide (600mg/m2) given IV every 14 days X 4 cycles
  • Paclitaxel
  • Carboplatin
  • Doxorubicin
  • Cyclophosphamide
Carboplatin + DocetaxelActive ComparatorCarboplatin (AUC 6) given IV and Docetaxel (75mg/m2) given IV every 21 days x 6 cycles
  • Carboplatin
  • Docetaxel

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with newly diagnosed stage I (T>1cm), II or III triple negative breast cancer
             who have not had definitive breast surgery or received systemic chemotherapy

          -  The invasive tumor must be hormone receptor-poor, defined as both estrogen receptor
             and progesterone receptor staining present in ≤ 10% of invasive cancer cells by
             Immunohistochemistry.

          -  HER- 2 negativity will be based on the current ASCO-CAP guidelines for HER testing

          -  No prior chemotherapy, endocrine therapy or radiation therapy with therapeutic intent
             for this cancer

          -  Female subjects age 18 - 70 years

          -  ECOG Performance Status of 0-1

          -  Adequate organ and marrow function as defined below:

               -  Leukocytes ≥ 3,000/uL

               -  Absolute neutrophil count ≥ 1500/uL

               -  Platelets ≥ 100,000/uL

               -  Total bilirubin ≤ 1.5mg/dL

               -  AST(SGOT)/ALT(SPGT) ≤ 2 x institutional upper limit of normal

               -  Creatinine ≤ 1.5mg/dl and/or Creatinine Clearance ≥ 60mL/min

               -  Serum albumin ≥ 3.0 g/dL

          -  Women of child-bearing potential must agree to use adequate contraception

          -  Pretreatment lab values must be performed within 14 days of treatment initiation, and
             other baseline studies performed within 30 days prior to registration

          -  Subjects should have LVEF ≥ 50% by echocardiogram or MUGA scan performed within 4
             weeks prior to treatment initiation

          -  Subjects should have breast and axillary imaging with breast MRI or breast and
             axillary ultrasound within 4 weeks prior to treatment initiation

          -  Subjects with clinically/radiologically abnormal axillary lymph nodes should have
             pathological confirmation of disease with image guided biopsy/fine needle aspiration.

          -  Subjects must be already enrolled in P.R.O.G.E.C.T observational registry

          -  Staging to rule out metastatic disease is recommended for subjects with clinical stage
             III disease

          -  Subjects with bilateral disease are eligible if they meet other eligibility criteria.

          -  Neuropathy: No baseline neuropathy grade > 2

        Exclusion Criteria:

          -  Current or anticipated use of other investigational agents

          -  Subject has received chemotherapy, radiotherapy or surgery for the treatment of breast
             cancer

          -  Subject with metastatic disease

          -  History of allergic reactions to compounds of similar chemical or biologic composition
             to carboplatin, docetaxel, doxorubicin, cyclophosphamide, paclitaxel, or other agents
             used in the study

          -  Subjects with inflammatory breast cancer

          -  Uncontrolled intercurrent illness including, but not limited to ongoing or active
             infection or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  Subject is pregnant or nursing

          -  Subjects with concomitant or previous malignancies within the last 5 years. Exceptions
             include: adequately treated basal or squamous cell carcinoma of the skin, carcinoma in
             situ of the cervix, and ductal carcinoma in situ (DCIS).

          -  Ejection Fraction <50% on ECHO or MUGA

          -  Cardiac function: Subjects with congestive heart failure, myocardial infarction,
             unstable angina pectoris, an arterial thrombotic event, stroke or transient ischemia
             attack within the past 12 months, uncontrolled hypertension (Systolic BP>160 or
             Diastolic BP>90), uncontrolled or symptomatic arrhythmia, or grade ≥ 2 peripheral
             vascular disease
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants With Pathological Complete Response
Time Frame:20 weeks
Safety Issue:
Description:To evaluate the pathological complete response rates with neoadjuvant chemotherapy regimens of carboplatin plus paclitaxel x 4 cycles followed by doxorubicin plus cyclophosphamide X 4 cycles and carboplatin plus docetaxel X 6 cycles in subjects with stage I-III triple-negative breast cancer. Pathological complete response is defined as no evidence of disease in the breast and axilla at the time of pathology review except for DCIS.

Secondary Outcome Measures

Measure:Number of Participants With Minimal Residual Disease
Time Frame:20 weeks
Safety Issue:
Description:To evaluate minimal residual disease rates (residual cancer burden 0+1) with two neoadjuvant chemotherapy regimens in subjects with stage I-III triple-negative breast cancer.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Priyanka Sharma

Trial Keywords

  • TNBC, breast cancer, neoadjuvant, carboplatin, docetaxel, paclitaxel, doxorubicin, cyclophosphamide

Last Updated

May 10, 2021