Clinical Trials /

Neoadjuvant Carbo/Paclitaxel Followed by Doxorubicin/Cyclophosphamide in Breast Cancer

NCT03301350

Description:

This is a phase II single-arm, open-label, prospective study to evaluate the efficacy of the low dose weekly Carboplatin/Paclitaxel followed by dose-dense Doxorubicin/Cyclophosphamide in subjects with triple-negative breast cancer in neoadjuvant settings.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Suspended

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Neoadjuvant Carbo/Paclitaxel Followed by Doxorubicin/Cyclophosphamide in Breast Cancer
  • Official Title: A Phase II Study of Neoadjuvant Carboplatin/Paclitaxel Followed by Dose-Dense Doxorubicin/Cyclophosphamide in Patients With Hormone Receptor Negative, HER2 Receptor Negative Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: UW16112
  • SECONDARY ID: P30CA014520
  • SECONDARY ID: NCI-2017-01705
  • SECONDARY ID: 2017-0547
  • NCT ID: NCT03301350

Conditions

  • Breast Cancer
  • Triple Negative Breast Cancer

Interventions

DrugSynonymsArms
CarboplatinNeoadjuvant Chemotherapy
PaclitaxelNeoadjuvant Chemotherapy
DoxorubicinAdriamycin, Doxil, Caelyx, MyocetNeoadjuvant Chemotherapy
CyclophosphamidecytophosphaneNeoadjuvant Chemotherapy

Purpose

This is a phase II single-arm, open-label, prospective study to evaluate the efficacy of the low dose weekly Carboplatin/Paclitaxel followed by dose-dense Doxorubicin/Cyclophosphamide in subjects with triple-negative breast cancer in neoadjuvant settings.

Trial Arms

NameTypeDescriptionInterventions
Neoadjuvant ChemotherapyExperimentalPaclitaxel 80 mg/m2; administer intravenously on day 1, 8, 15 of cycles 1, 2, 3, 4 (every 3 weeks) Carboplatin AUC=2; administer intravenously on day 1, 8, 15 of cycles 1, 2, 3, 4 (every 3 weeks) Doxorubicin 60 mg/m2; administer intravenously on day 1 of cycles 5, 6, 7, 8 (every 2 weeks) Cyclophosphamide 600 mg/m2; administer intravenously on day 1 of cycles 5, 6, 7, 8 (every 2 weeks) Pegfilgrastim, filgrastim, or biosimilar support on day 2 - 3 of cycles 5, 6, 7, 8 (every 2 weeks) Surgical intervention for management of breast cancer diagnosis; procedure and timing as determined by surgical team.
  • Carboplatin
  • Paclitaxel
  • Doxorubicin
  • Cyclophosphamide

Eligibility Criteria

        Inclusion Criteria:

          1. Subjects must have histologically or cytologically confirmed invasive breast cancer
             which meets the following criteria:

               1. Estrogen Receptor (ER) and Progesterone Receptor (PR)-negative as defined by
                  local standard clinical immunohistochemistry (IHC) < 1%.

               2. HER2-negative using local standard testing. Negative is defined as IHC 0 or 1+
                  (if 2+, must reflex to ISH method). If ISH method is used, ratio < 2 is
                  considered negative.

               3. Clinical tumor size of at least 2.1 cm regardless the ipsilateral regional lymph
                  node status, or any tumor size but with ipsilateral regional lymph nodes involved
                  by the tumor. Subjects with inflammatory breast cancer are eligible. If bilateral
                  breast cancer is present, the subject is eligible if the contralateral tumor is
                  DCIS only (without any invasive disease on biopsy) or another invasive breast
                  cancer of any size that is also ER, PR and HER2 negative.

               4. Any radiographic abnormal ipsilateral regional lymph nodes or any palpable
                  ipsilateral regional lymph nodes should be biopsied. No sentinel ipsilateral
                  axillary lymph node biopsy is allowed. If clinically node negative (cNO),,
                  sentinel ipsilateral axillary lymph node biopsy is not allowed.

          2. Candidate for neoadjuvant chemotherapy.

          3. Age > 18 years.

          4. ECOG Performance Status < 1.

          5. Left ventricular ejection fraction (LVEF) ≥ LLN (per institutional normal) determined
             by

          6. Adequate organ and marrow function as determined by study protocol

          7. Non Pregnant. Women of childbearing potential must have a negative pregnancy test (HCG
             serum or urine) within 30 days prior to study registration and to be repeated if not
             done within 7 days of starting chemotherapy.

               1. Female subjects must meet one of the following:

                    -  Natural postmenopausal before the screening visit defined as no menses at
                       any time in the preceding 12 consecutive months, or

                    -  Prior bilateral oophorectomy or bilateral tubal ligation, or

                    -  If they are of childbearing potential, agree to practice two effective
                       methods of contraception per discussion with the treating physicians from

               2. Male subjects, even if surgically sterilized (i.e., status post vasectomy) must
                  agree to one of the following:

                    -  Practice effective barrier contraception during the entire study treatment
                       period and through 90 days after the last study drug dose, or

                    -  Agree to practice true abstinence when this is in line with the preferred
                       and usual lifestyle of the subject. (Periodic abstinence (e.g., calendar,
                       ovulation, symptothermal, postovulation methods] and withdrawal are not
                       acceptable methods of contraception.)

          8. Ability to understand a written informed consent document, and the willingness to sign
             it.

        Exclusion Criteria:

          1. Prior chemotherapy or radiation therapy for invasive breast cancer within 6 months
             before registration.

          2. Prior investigational drugs for invasive breast cancer within 6 months before
             registration.

          3. Stage IV metastatic breast cancer

          4. History of allergic reactions attributed to compounds of similar chemical composition
             to chemotherapy to be used in this study.

          5. Breastfeeding women. Cytotoxic chemotherapy is drug with the potential for teratogenic
             or abortifacient effects. Due to unknown but potential risk for adverse events in
             nursing infants secondary to treatment of the mother with cytotoxic chemotherapy,
             breastfeeding should be discontinued.

          6. Baseline peripheral neuropathy of severity > grade 1

          7. Other invasive cancer diagnosis within the past 5 years other than non-melanoma skin
             cancer.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Pathologic Complete Response (pCR) rate
Time Frame:Up to 2 years
Safety Issue:
Description:pCR is defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy. pCR will be assessed according to RECIST 1.1 criteria. The point estimate of the primary efficacy endpoint pCR and its exact 95% confidence intervals (CI) will be calculated. In evaluating pCR, subjects with missing data will be considered non-responders.

Secondary Outcome Measures

Measure:Number of cycles, doses, and delays of chemotherapy administered
Time Frame:Up to week 12
Safety Issue:
Description:To evaluate the number of cycles, doses and delays of low dose weekly Carboplatin/Paclitaxel regimen administered. Simple descriptive statistics will be used to describe the number of cycles, doses, and delays of chemotherapy administered.
Measure:Number of treatment-related toxicities experienced by participants
Time Frame:Up to week 12
Safety Issue:
Description:Count of any treatment-related toxicities from the low dose weekly Carboplatin/Paclitaxel regimen. Will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Measure:Recurrence-free survival (RFS)
Time Frame:Up to 2 years
Safety Issue:
Description:To evaluate two-year RFS after treatment with this neoadjuvant regimen. Disease-free/recurrence-free survival is defined as the duration for which the participant is without evidence for local-regional or distant relapse, second primary, or death. The median RFS will be obtained by the Kaplan-Meier technique. The 95% confidence interval will be calculated.
Measure:Overall survival (OS)
Time Frame:Up to 2 years
Safety Issue:
Description:To evaluate the two-year overall survival after treatment with this neoadjuvant regimen. OS is defined as the time from initiation of study until death from any cause. The median OS will be obtained by the Kaplan-Meier technique. The 95% confidence interval will be calculated.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Wisconsin, Madison

Last Updated

October 3, 2017