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

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ClinicalTrials.gov Identifier: NCT03301350
Recruitment Status : Recruiting
First Posted : October 4, 2017
Last Update Posted : July 11, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Wisconsin, Madison

Tracking Information
First Submitted Date  ICMJE September 29, 2017
First Posted Date  ICMJE October 4, 2017
Last Update Posted Date July 11, 2019
Actual Study Start Date  ICMJE November 7, 2017
Estimated Primary Completion Date October 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 3, 2017)
Pathologic Complete Response (pCR) rate [ Time Frame: Up to 2 years ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03301350 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 9, 2018)
  • Number of cycles of chemotherapy administered [ Time Frame: Week 12 to week 18 to account for possible delays ]
    To evaluate the number of cycles low dose weekly Carboplatin/Paclitaxel regimen administered. Simple descriptive statistics will be used to describe the number of cycles of chemotherapy administered.
  • Total dose of chemotherapy administered [ Time Frame: Week 12 to week 18 to account for possible delays ]
    To evaluate the total dose of weekly Carboplatin/Paclitaxel regimen administered. Simple descriptive statistics will be used to describe the dose amount of chemotherapy administered.
  • Delays of administered chemotherapy [ Time Frame: Week 12 to week 18 to account for possible delays ]
    To evaluate the delays of low dose weekly Carboplatin/Paclitaxel regimen administered. Simple descriptive statistics will be used to describe the delays of chemotherapy administered.
  • Number of treatment-related toxicities experienced by participants [ Time Frame: Up to week 12 ]
    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
  • Recurrence-free survival (RFS) [ Time Frame: Up to 2 years ]
    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.
  • Overall survival (OS) [ Time Frame: Up to 2 years ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 3, 2017)
  • Number of cycles, doses, and delays of chemotherapy administered [ Time Frame: Up to week 12 ]
    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.
  • Number of treatment-related toxicities experienced by participants [ Time Frame: Up to week 12 ]
    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
  • Recurrence-free survival (RFS) [ Time Frame: Up to 2 years ]
    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.
  • Overall survival (OS) [ Time Frame: Up to 2 years ]
    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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Neoadjuvant Carbo/Paclitaxel Followed by Doxorubicin/Cyclophosphamide in Breast Cancer
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Breast Cancer
  • Triple Negative Breast Cancer
Intervention  ICMJE
  • Drug: Carboplatin
    Carboplatin is a platinum compound alkylating agent which covalently binds to DNA; interferes with the function of DNA by producing interstrand DNA cross-links.
  • Drug: Paclitaxel
    Paclitaxel promotes microtubule assembly by enhancing the action of tubulin dimers, stabilizing existing microtubules, and inhibiting their disassembly, interfering with the late G2 mitotic phase, and inhibiting cell replication. In addition, the drug can distort mitotic spindles, resulting in the breakage of chromosomes. Paclitaxel may also suppress cell proliferation and modulate immune response.
  • Drug: Doxorubicin
    Inhibition of DNA and RNA synthesis by intercalation between DNA base pairs by inhibition of topoisomerase II and by steric obstruction. Doxorubicin intercalates at points of local uncoiling of the double helix. Although the exact mechanism is unclear, it appears that direct binding to DNA (intercalation) and inhibition of DNA repair (topoisomerase II inhibition) result in blockade of DNA and RNA synthesis and fragmentation of DNA. Doxorubicin is also a powerful iron chelator; the iron-doxorubicin complex can bind DNA and cell membranes and produce free radicals that immediately cleave the DNA and cell membranes.
    Other Names:
    • Adriamycin
    • Doxil
    • Caelyx
    • Myocet
  • Drug: Cyclophosphamide
    Cyclophosphamide is an alkylating agent that prevents cell division by cross-linking DNA strands and decreasing DNA synthesis. It is a cell cycle phase nonspecific agent. Cyclophosphamide also possesses potent immunosuppressive activity. Cyclophosphamide is a prodrug that must be metabolized to active metabolites in the liver.
    Other Name: cytophosphane
  • Drug: Pegfilgrastim
    Pegfilgrastim provides growth factor support in a single dose. It stimulates bone marrow to create neutrophils for patients undergoing chemotherapy.
  • Drug: Filgrastim
    Filgrastim provides growth factor support in multiple doses. It stimulates bone marrow to create neutrophils for patients undergoing chemotherapy.
Study Arms  ICMJE Experimental: Neoadjuvant Chemotherapy

Paclitaxel 80 mg/m2; administer intravenously on day 1, 8, 15 of cycles 1, 2, 3, 4 (every 3 weeks) Carboplatin AUC=2 (dose calculation by determining creatine clearance with Cockroft Gault using adjusted body weight); 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 (for use on Doxorubicin/Cyclophosphamide cycles only), filgrastim, or biosimilar support on day 2 - 3 of cycles 5, 6, 7, 8 (every 2 weeks)

There is a one week break between the end of cycle 4 and the beginning of cycle 5.

Surgical intervention for management of breast cancer diagnosis; procedure and timing as determined by surgical team.

Interventions:
  • Drug: Carboplatin
  • Drug: Paclitaxel
  • Drug: Doxorubicin
  • Drug: Cyclophosphamide
  • Drug: Pegfilgrastim
  • Drug: Filgrastim
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 3, 2017)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2022
Estimated Primary Completion Date October 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 (T2) by palpation or imaging, regardless of the ipsilateral regional lymph node status, or any tumor size but with ipsilateral regional lymph nodes involved by the tumor (any T if ipsilateral regional node positive). 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 clinically concerning ipsilateral regional lymph nodes with the exception of internal mammary nodes should be sampled with percutaneous biopsy, but no sentinel axillary lymph node mapping/biopsy is allowed before chemotherapy. If clinically node negative (cNO), pre-chemotherapy ipsilateral sentinel axillary lymph node mapping/biopsy is not allowed.
  2. Candidate for neoadjuvant chemotherapy.
  3. Age > 18 years and < 75 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 or interventions for invasive breast cancer within 6 months before registration are not allowed. Prior participation in window-of-opportunity trials without therapeutic intent is allowed if intervention is no more than 3 weeks duration.
  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.
  8. Prior axillary lymph node dissection that preclude patient from surgical evaluation of axillary lymph node status.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 74 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Cancer Connect 800-622-8922 skotila@wisc.edu
Contact: WON Wisconsin Oncology Network 608-265-5676 affiliatecoordinators@uwcarbone.wisc.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03301350
Other Study ID Numbers  ICMJE UW16112
P30CA014520 ( U.S. NIH Grant/Contract )
NCI-2017-01705 ( Registry Identifier: NCI CTRP )
2017-0547 ( Other Identifier: UW IRB )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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.: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Wisconsin, Madison
Study Sponsor  ICMJE University of Wisconsin, Madison
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Kari Wisinski, MD University of Wisconsin, Madison
PRS Account University of Wisconsin, Madison
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP