Clinical trial NCT03301350: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Triple Negative Breast Cancer
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
First posted: 2017-10-04
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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 (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.

Primary outcomes:
measure: Number and Percentage of Participants With Pathologic Complete Response (pCR) Rate
timeFrame: Up to 2 years
Secondary outcomes:
measure: Number of Cycles of Chemotherapy Administered
timeFrame: Week 12 to week 18 to account for possible delays
measure: Total Dose of Chemotherapy Administered
timeFrame: Week 12 to week 18 to account for possible delays
measure: Delays of Administered Chemotherapy
timeFrame: Week 12 to week 18 to account for possible delays
measure: Number of Treatment-related Toxicities Experienced by Participants
timeFrame: Up to week 12
measure: Recurrence-free Survival (RFS)
timeFrame: Up to 2 years
measure: Overall Survival (OS)
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Rockford
country: United States
facility: Swedish American Hospital
state: Illinois
city: Madison
country: United States
facility: University of Wisconsin Carbone Cancer Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Columbia St. Mary's Cancer Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Waukesha
country: United States
facility: ProHealth Care
state: Wisconsin
city: Wausau
country: United States
facility: Aspirus Regional Cancer Center Wausau
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: Kari Wisinski, MD
role: PRINCIPAL_INVESTIGATOR
References: