Neoadjuvant Study of Two Platinum Regimens in Triple Negative Breast Cancer (NeoSTOP)

May 6, 2021 updated by: Priyanka Sharma

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

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.

Study Overview

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.

Study Type

Interventional

Enrollment (Actual)

101

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Kansas
      • Fairway, Kansas, United States, 66205
        • University of Kansas Cancer Center - CRC
      • Hays, Kansas, United States, 67601
        • Hays Medical Center
      • Overland Park, Kansas, United States, 66210
        • University of Kansas Cancer Center - Overland Park
      • Salina, Kansas, United States, 67401
        • Salina Regional Health Center
      • Westwood, Kansas, United States, 66205
        • University of Kansas Cancer Center - Westwood
    • Missouri
      • Kansas City, Missouri, United States, 64154
        • University of Kansas Cancer Center - North
      • Kansas City, Missouri, United States, 64108
        • Truman Medical Center
      • Kansas City, Missouri, United States, 64131
        • University of Kansas Cancer Center - South
      • Lee's Summit, Missouri, United States, 64064
        • University of Kansas Cancer Center - Lee's Summit

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Carboplatin + Paclitaxel then Doxorubicin + Cyclophosphamide
Paclitaxel (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
Other Names:
  • cytoxin, procytox
Other Names:
  • adriamycin
Other Names:
  • paraplatin
Other Names:
  • taxol
Active Comparator: Carboplatin + Docetaxel
Carboplatin (AUC 6) given IV and Docetaxel (75mg/m2) given IV every 21 days x 6 cycles
Other Names:
  • taxotere
Other Names:
  • paraplatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Pathological Complete Response
Time Frame: 20 weeks
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.
20 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Minimal Residual Disease
Time Frame: 20 weeks
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.
20 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Principal Investigator: Priyanka Sharma, MD, University of Kansas Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2015

Primary Completion (Actual)

February 1, 2019

Study Completion (Actual)

February 1, 2020

Study Registration Dates

First Submitted

April 6, 2015

First Submitted That Met QC Criteria

April 8, 2015

First Posted (Estimate)

April 9, 2015

Study Record Updates

Last Update Posted (Actual)

May 10, 2021

Last Update Submitted That Met QC Criteria

May 6, 2021

Last Verified

May 1, 2021

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Triple-negative Breast Cancer

Clinical Trials on Docetaxel

3
Subscribe