Clinical Trials /

Phase 2 Trial of Neoadjuvant Weekly Carboplatin Plus Paclitaxel in Triple Negative Breast Cancer

NCT04083963

Description:

Nonrandomized, open label, single arm study of neoadjuvant weekly carboplatin plus paclitaxel, followed by doxorubicin and cyclophosphamide in patients with operable Triple Negative Breast Cancer (TNBC)

Related Conditions:
  • Invasive Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase 2 Trial of Neoadjuvant Weekly Carboplatin Plus Paclitaxel in Triple Negative Breast Cancer
  • Official Title: BRE-01: Phase 2 Trial of Neoadjuvant Weekly Carboplatin Plus Paclitaxel Followed by Doxorubicin and Cyclophosphamide in Triple Negative Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: 2019-0550
  • NCT ID: NCT04083963

Conditions

  • Triple Negative Breast Cancer

Interventions

DrugSynonymsArms
CarboplatinParaplatinSingle arm
PaclitaxelTaxolSingle arm
DoxorubicinAdriamycinSingle arm
CyclophosphamideCytoxanSingle arm

Purpose

Nonrandomized, open label, single arm study of neoadjuvant weekly carboplatin plus paclitaxel, followed by doxorubicin and cyclophosphamide in patients with operable Triple Negative Breast Cancer (TNBC)

Detailed Description

      This is a single arm, Phase 2, open label, study to evaluate the safety and efficacy of
      weekly carboplatin in combination with standard neoadjuvant chemotherapy in subjects with
      previously untreated triple negative breast cancers who are candidates for potentially
      curative surgery.

      Subjects will receive carboplatin (Area Under the Curve (AUC) 2 mg/mL/min) + paclitaxel (80
      mg/m2) Carboplantin plus Paclitaxel (CbP) followed by doxorubicin and cyclophosphamide (AC).
      All subjects will receive CbP on Day 1 of 12 weekly cycles (Visits CbP1 - CbP12) via infusion
      during Chemotherapy Segment 1 as indicated in the Study Schema. Dose interruptions and dose
      modifications are allowed based upon tolerability and may extend Chemotherapy Segment 1
      duration to a maximum of 16 weeks. Beginning with Chemotherapy Segment 2 all subjects will
      receive doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) on Day 1 of four 14-day
      cycles (Visits AC1 - AC4). For subjects who experience toxicities due to carboplatin,
      paclitaxel, doxorubicin or cyclophosphamide, the appropriate dose modifications or dosing
      delays should be managed according to Section 11.2. Dose modifications may result in the
      total duration of therapy being greater than the planned 24 weeks. The objective of this
      study is to determine efficacy and tolerability of low dose, weekly carboplatin in
      combination with weekly paclitaxel followed by standard doxorubicin/cyclophosphamide as
      neoadjuvant therapy for triple-negative breast cancer.
    

Trial Arms

NameTypeDescriptionInterventions
Single armOtherLow dose weekly carboplatin in combination with standard neoadjuvant chemotherapy
  • Carboplatin
  • Paclitaxel
  • Doxorubicin
  • Cyclophosphamide

Eligibility Criteria

        Inclusion Criteria:

          1. Female ≥ 18 years of age at time of consent.

          2. Histologically confirmed invasive breast carcinoma documented by core needle biopsy or
             incisional biopsy (excisional biopsy is not allowed). AJCC 8th edition clinical stage
             cT2-4, N0-3 or cT1, N1-3 by physical exam or radiologic studies. Suspected involvement
             of regional lymph nodes based on physical exam or imaging studies must be confirmed
             cytologically/histologically.

          3. Surgical excision of the primary breast tumor (partial mastectomy or total mastectomy)
             and ipsilateral axillary lymph node sampling (sentinel lymph node biopsy or axillary
             dissection) are planned following neoadjuvant chemotherapy.

          4. Estrogen Receptor (ER)- and Progesterone Receptor (PR)-negative, and Human Epidermal
             Growth Factor Receptor (HER)2-negative (triple-negative) cancer of the breast.

             Triple-negative tumors are defined as:

               -  ER- and PR-negative: less than or equal to 10% tumor staining by
                  immunohistochemistry (IHC) according to local pathology assessment.

               -  HER2-negative disease, defined as defined by ASCO/CAP guidelines [24]. Eastern
                  Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 within 28 days
                  prior to study registration.

          5. Life expectancy of 6 months or greater as determined by the treating physician.

          6. Demonstrate adequate organ function as defined in the table below; all screening labs
             to be obtained within 28 days prior to registration.

             System Hematological Leukocytes

               -  2,500/mm3 Platelet count

               -  100,000/mm3 Absolute Neutrophil Count (ANC)

               -  1,500/mm3 Hemoglobin (Hgb)

               -  9.5 g/dL Renal Creatinine/Calculated creatinine clearance (CrCl) Cr < 1.5 x upper
                  limit of normal (ULN) or CrCl ≥ 50 mL/min using the Cockcroft-Gault formula
                  Hepatic Bilirubin Bilirubin ≤ 1.5 × ULN. Subjects with Gilbert's syndrome may
                  have a bilirubin > 1.5 × ULN, if no evidence of biliary obstruction exists
                  Aspartate aminotransferase (AST)

                    -  2.5 × ULN Alanine aminotransferase (ALT)

                    -  2.5 × ULN

          7. No evidence of distant metastases (M0 as per AJCC staging guidelines) Weekly
             Carboplatin for TNBC Confidential Protocol v.1.0, dated February 10, 2019 Page 19 of
             64

          8. Provided written informed consent and HIPAA authorization for release of personal
             health information, approved by an Institutional Review Board (IRB).

          9. NOTE: HIPAA authorization may be included in the informed consent or obtained
             separately.

         10. Women of childbearing potential (WOCP) must not be pregnant or breast-feeding. A
             negative serum or urine pregnancy test is required within 14 days of study
             registration. If the urine test cannot be confirmed as negative, a serum pregnancy
             test will be required.

         11. Women of childbearing potential (WOCP) must be willing to use two effective methods of
             birth control such as an oral, implantable, injectable, or transdermal hormonal
             contraceptive, an intrauterine device (IUD), use of a double barrier method (condoms,
             sponge, diaphragm, or vaginal ring with spermicidal jellies or cream), or total
             abstinence for the course of the study until 90 days after the last dose of study
             drug.

             NOTE: Women are considered to be of childbearing potential unless they are
             postmenopausal (≥45 years of age and has not had menses for greater than 12
             consecutive months or bilateral oophorectomy) or surgically sterile (bilateral tubal
             ligation or hysterectomy) or not heterosexually active for the duration of the study
             and at least 60 days after the last dose of study drug.

         12. As determined by the enrolling physician or protocol designee, ability of the subject
             to understand and comply with study procedures for the entire length of the study.

        Exclusion Criteria:

          1. Active infection requiring systemic therapy.

          2. Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the
             mother is being treated on study).

          3. Previous anti-cancer treatment (cytotoxic chemotherapy, immunotherapy, biologic
             therapy, radiotherapy directed towards the primary breast tumor and/or ipsilateral
             axillary lymph nodes or investigational agents) with therapeutic intent for the
             current breast cancer.

          4. Previous treatment with carboplatin, paclitaxel, doxorubicin, or cyclophosphamide
             within the past 3 years.

          5. Concurrent treatment with an ovarian hormonal replacement therapy or with hormonal
             agents such as raloxifene, tamoxifen or other selective estrogen receptor modulator
             (SERM). Subjects must have discontinued use of such agents prior to beginning study
             treatment.

          6. A history of seizure within 6 months prior to study entry.

          7. Pre-existing neuropathy from any cause in excess of Grade 1.

          8. Treatment with any investigational drug within 14 days prior to registration or within
             5 half-lives of the investigational product, whichever is longer.

          9. Major surgery within 14 days prior to registration or has not recovered from major
             side effects

         10. Any prior or concurrent malignancy whose natural history or treatment has the
             potential to interfere with the safety or efficacy assessment of this investigational
             regimen, as determined by the treating Medical Oncologist.

         11. Known history of AIDS (HIV testing is not mandatory). HIV-positive individuals on
             active HARRT therapy with virologic suppression (defined as an HIV-1 RNA level below
             the lower limit of detection of the assay used) within 90 days of study enrollment and
             a CD4 cell count >500 cells/mm3 on the most recent determination are eligible for the
             study.

         12. History of myelodysplastic syndrome or acute myeloid leukemia.

         13. Subjects with any of the following conditions:

               -  History of abdominal fistula, gastrointestinal perforation, or intra- abdominal
                  abscess within 28 days prior to registration.

               -  History of cerebrovascular accident (CVA) or transient ischemic attack within 6
                  months prior to registration.

               -  History of acute coronary syndromes (including myocardial infarction, unstable
                  angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or
                  symptomatic pericarditis within 6 months prior to registration.

               -  Symptomatic congestive heart failure (New York Heart Association III-IV) or
                  documented current left ventricular (LV) systolic dysfunction with left
                  ventricular ejection fraction (LVEF) <50% on most recent assessment of LV
                  function.

               -  Clinically significant cardiac ventricular arrhythmias (e.g. sustained
                  ventricular tachycardia/ventricular fibrillation) or high-grade AV block (e.g.
                  bifascicular block, Mobitz type II and third-degree AV block) unless a pacemaker
                  is in place.

               -  Any concurrent severe and/or uncontrolled medical condition that would, in the
                  investigator's judgment, cause unacceptable safety risks, contraindicate subject
                  participation in the clinical study or compromise compliance with the protocol.

         14. Any condition that, in the opinion of the investigator, might jeopardize the safety of
             the patient or interfere with protocol compliance.

         15. Any mental or medical condition that prevents the patient from giving informed
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Pathological complete response (pCR) rate
Time Frame:30 months
Safety Issue:
Description:Defined as the absence of residual invasive carcinoma in the resected breast specimen and ipsilateral axillary lymph nodes following completion of neoadjuvant therapy (i.e., ypT0/Tis, ypN0 per the American joint Committee on Cancer staging system) in all subjects completing at least 1 cycle of study treatment (modified intent-to-treat population)

Secondary Outcome Measures

Measure:Pathologic complete response rate in subjects completing protocol therapy.
Time Frame:30 months
Safety Issue:
Description:Pathologic complete response rate Defined as the absence of residual invasive carcinoma in the resected breast specimen and ipsilateral axillary lymph nodes following completion of neoadjuvant therapy (i.e., ypT0/Tis, ypN0 per the American joint Committee on Cancer staging system) will be determined in the sub-group of subjects completing at least 75% of planned treatment cycles.
Measure:Residual Cancer Burden
Time Frame:30 months
Safety Issue:
Description:The Residual Cancer Burden (RCB) class will be estimated from routine pathologic sections of the resected primary breast tumor and the regional lymph nodes after the completion of neoadjuvant therapy. RCB class 0 represents pCR, and class I represents minimal residual invasive disease. Class II and III represent significant residual disease. We will report the rate of achieving RCB class 0/1 vs. II/III.
Measure:Event-free survival (EFS)
Time Frame:30 months
Safety Issue:
Description:Time from enrollment to any of the following: failure to undergo potentially curative surgery; onset of local, regional, or distant invasive recurrence of breast cancer following curative surgery; second primary invasive cancer in the breast or in another organ; or death from any cause.
Measure:Invasive disease-free survival (iDFS)
Time Frame:30 months
Safety Issue:
Description:Time from enrollment to any of the following: development of invasive cancer in the ipsilateral breast or regional nodes, contralateral breast or regional nodes, distant metastases, or death from any cause
Measure:Distant disease-free survival (DDFS)
Time Frame:30 months
Safety Issue:
Description:Time from enrollment to documentation of distant metastases or death from any cause
Measure:Overall survival (OS)
Time Frame:30 months
Safety Issue:
Description:Time from enrollment to death from any cause
Measure:Clinical response to neoadjuvant chemotherapy
Time Frame:30 months
Safety Issue:
Description:Defined as progressive disease, stable disease, partial response and complete response according to RECIST 1.1 criteria in the modified intent-to-treat population and participants completing at least 75% of protocol therapy
Measure:Breast conservation rate
Time Frame:30 months
Safety Issue:
Description:The percentage of women undergoing adequate partial mastectomy as determined by treating physicians and achieving negative pathological surgical margins (no ink on tumor).
Measure:Treatment tolerability
Time Frame:30 months
Safety Issue:
Description:Number of cycles delayed, deleted or requiring dose reduction; number of participants who fail to complete all planned courses of protocol therapy; number of participants with treatment-related adverse events as assessed by CTCAE v5.0.
Measure:Quality of life Measurement
Time Frame:30 months
Safety Issue:
Description:Change in score on the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 quality of life survey. This 30-item survey uses a Likert scale with total scores ranging from 30-126, with increasing scores indicating worse quality of life. We will compare mean baseline scores to scores at the end of protocol therapy, and 3 and 12 months after completing all protocol therapy.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Illinois at Chicago

Last Updated

February 10, 2020