Neoadjuvant Treatment of Triple Negative Breast Cancer Patients With Docetaxel and Carboplatin to Assess Anti-tumor Activity

A Co-clinical Trial in Triple Negative Breast Cancer Patients With Genoproteomic Discovery

This is a single arm open label phase II study in women with clinical stage 2 or 3 triple negative breast cancer to assess the anti-tumor activity (in terms of pathologic complete response rate) of neoadjuvant docetaxel in combination with carboplatin. Patient derived xenografts will also be developed simultaneously for the purposes of genoproteomic analysis.

Please note that Baylor College of Medicine (BCM) has a parallel study the same as this study. Baylor is expected to enroll approximately 19 participants that have complied with the inclusion and exclusion criteria for this study (excluded participants from BCM will include male participants or participants with inflammatory breast cancer). The investigators will pool participants and data from the BCM study and the study at Washington University School of Medicine. Pooling the data will potentially improve statistical power.

Study Overview

• Status: Terminated
• Conditions: Triple Negative Breast Neoplasms
• Intervention / Treatment: Drug: Docetaxel; Drug: Carboplatin; Procedure: FDG-PET/MR

• Study Type: Interventional
• Enrollment (Actual): 148
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Newly diagnosed AJCC7 clinical stage II or III breast cancer with complete surgical excision of the breast cancer after neoadjuvant chemotherapy as the treatment goal.
• Patients with PR+ tumors are allowed.
• HER2 negative by FISH or IHC staining 0 or 1+.
• ER less than Allred score of 3 or less than 1% positive staining cells in the invasive component of the tumor
• Tumor size at least 2cm in one dimension by clinical or radiographic exam (WHO criteria). Patients with palpable lymph nodes may be enrolled regardless of tumor size.
• At least 18 years of age.
• ECOG performance status ≤ 2

• Normal bone marrow and organ function as defined below:

  • Leukocytes ≥ 3,000/mcL
  • Absolute neutrophil count ≥ 1,500/mcl
  • Platelets ≥ 100,000/mcl
  • Serum bilirubin within (or under ) normal limits (OR total bilirubin ≤ 3.0 x IULN with direct bilirubin within normal range in patients with well documented Gilbert Syndrome)
  • AST(SGOT)/ALT(SGPT) within (or under ) normal limits
  • Creatinine clearance ≥ 60 mL/min/1.73 m2
• Patients may be pre- or post-menopausal. Women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
• Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
• Able to tolerate PET/MRI with intravenous contrast administration and must complete the applicable MRI screening evaluation form

Exclusion Criteria:

• Prior systemic therapy for the indexed breast cancer.
• A history of other malignancy ≤ 5 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix.
• Patients with bilateral or inflammatory breast cancer.
• Currently receiving any other investigational agents.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to docetaxel or carboplatin.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant and/or breastfeeding. Patient must have a negative serum pregnancy test within 7 days of study entry if premenopausal.
• Known HIV-positivity.
• Sentinel lymph node biopsy
• Renal insufficiency (glomerular filtration rate (GFR) < 30 mL/min/1.73 m2) measured within the past 60 days which precludes safe administration of the contrast agent
• On dialysis
• Prior allergic reaction to gadolinium-based MR contrast agents

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Washington University: Neoadjuvant docetaxel and carboplatin; Docetaxel will be administered intravenously at a dose of 75mg/m2 over 60 minutes on Day 1 of each 21-day cycle. Carboplatin AUC 6 will be administered intravenously over 30 minutes on Day 1 of each 21-day cycle immediately following docetaxel infusion. A total of 6 cycles will be given.	Drug: Docetaxel; Other Names: Docefrez®, Taxotere®; Drug: Carboplatin; Other Names: Paraplatin, Paraplatin-AQ; Procedure: FDG-PET/MR; Prior to initialization of Cycle 1 and completion of cycle 1 (preferably on cycle 2 day 1); This is not optional for final 30 participants enrolled on the study
EXPERIMENTAL: Baylor: Neoadjuvant docetaxel and carboplatin; Docetaxel will be administered intravenously at a dose of 75mg/m2 over 60 minutes on Day 1 of each 21-day cycle. Carboplatin AUC 6 will be administered intravenously over 30 minutes on Day 1 of each 21-day cycle immediately following docetaxel infusion.	Drug: Docetaxel; Other Names: Docefrez®, Taxotere®; Drug: Carboplatin; Other Names: Paraplatin, Paraplatin-AQ; Procedure: FDG-PET/MR; Prior to initialization of Cycle 1 and completion of cycle 1 (preferably on cycle 2 day 1); This is not optional for final 30 participants enrolled on the study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological Complete Response (pCR) Rate	-A patient is considered to not to have a pCR if any of the following are true: There is histologic evidence of invasive tumor cells in the surgical breast specimen or the axillary lymph nodes.; The patient has discontinued neoadjuvant treatment early due to refusal, toxicity, or radiographic evidence of progression and then goes straight to surgery where there is histologic evidence of invasive tumor cells in the surgical breast specimen and the axillary lymph nodes; The patient has discontinued neoadjuvant treatment early due to refusal, toxicity or radiographic evidence of progression and then receives alternative treatment.; The patient discontinues study treatment, refuses surgery, or is unable to undergo surgery due to a co-morbid condition. Thus, any patient who does not receive alternative treatment prior to surgery and has no histologic evidence of invasive tumor cells in the surgical breast specimen and the axillary lymph nodes is considered to have a pCR.	At the time of surgery (surgery will take place 3-5 weeks after completion of treatment and estimated treatment length is 18 weeks)

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: National Cancer Institute (NCI); National Institutes of Health (NIH); Breast Cancer Research Foundation; NeoImmune Tech
• Investigators: Principal Investigator: Foluso Ademuyiwa, M.D., MPH, Washington University School of Medicine

Publications and helpful links

General Publications

• Ademuyiwa FO, Chen I, Luo J, Rimawi MF, Hagemann IS, Fisk B, Jeffers G, Skidmore ZL, Basu A, Richters M, Ma CX, Weilbaecher K, Davis J, Suresh R, Peterson LL, Bose R, Bagegni N, Rigden CE, Frith A, Rearden TP, Hernandez-Aya LF, Roshal A, Clifton K, Opyrchal M, Akintola-Ogunremi O, Lee BH, Ferrando-Martinez S, Church SE, Anurag M, Ellis MJ, Gao F, Gillanders W, Griffith OL, Griffith M. Immunogenomic profiling and pathological response results from a clinical trial of docetaxel and carboplatin in triple-negative breast cancer. Breast Cancer Res Treat. 2021 Aug;189(1):187-202. doi: 10.1007/s10549-021-06307-3. Epub 2021 Jun 26.

Helpful Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 7, 2014
• Primary Completion (ACTUAL): November 10, 2021
• Study Completion (ACTUAL): December 31, 2021

Study Registration Dates

• First Submitted: April 24, 2014
• First Submitted That Met QC Criteria: April 24, 2014
• First Posted (ESTIMATE): April 28, 2014

Study Record Updates

• Last Update Posted (ACTUAL): November 7, 2022
• Last Update Submitted That Met QC Criteria: October 12, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel; Carboplatin
• Other Study ID Numbers: 201404107; 1U24CA209837-01A1 (NIH)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No