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.
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:
NCI-2017-01705
- SECONDARY ID:
2017-0547
- SECONDARY ID:
A534260
- SECONDARY ID:
SMPH\MEDICINE\HEM-ONC
- SECONDARY ID:
Protocol Version 11/26/2019
- NCT ID:
NCT03301350
Conditions
- Breast Cancer
- Triple Negative Breast Cancer
Interventions
Drug | Synonyms | Arms |
---|
Carboplatin | | Neoadjuvant Chemotherapy |
Paclitaxel | | Neoadjuvant Chemotherapy |
Doxorubicin | Adriamycin, Doxil, Caelyx, Myocet | Neoadjuvant Chemotherapy |
Cyclophosphamide | cytophosphane | Neoadjuvant Chemotherapy |
Pegfilgrastim | | Neoadjuvant Chemotherapy |
Filgrastim | | Neoadjuvant 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
Name | Type | Description | Interventions |
---|
Neoadjuvant Chemotherapy | Experimental | Regimen A (cycles 1-4):
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)
Regimen B (cycles 5-8):
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.
Regimen C:
Surgical intervention for management of breast cancer diagnosis; procedure and timing as determined by surgical team. | - Carboplatin
- Paclitaxel
- Doxorubicin
- Cyclophosphamide
- Pegfilgrastim
- Filgrastim
|
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.
Maximum Eligible Age: | 74 Years |
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 of chemotherapy administered |
Time Frame: | Week 12 to week 18 to account for possible delays |
Safety Issue: | |
Description: | 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. |
Measure: | Total dose of chemotherapy administered |
Time Frame: | Week 12 to week 18 to account for possible delays |
Safety Issue: | |
Description: | 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. |
Measure: | Delays of administered chemotherapy |
Time Frame: | Week 12 to week 18 to account for possible delays |
Safety Issue: | |
Description: | 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. |
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: | Active, not recruiting |
Lead Sponsor: | University of Wisconsin, Madison |
Last Updated
April 1, 2021