Back to resultsFeasibility of Chemotherapy De-escalation in Early-Stage HER2 Positive Breast Cancer
Primary Purpose
HER2-positive Breast Cancer
Status
Suspended
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Docetaxel
Carboplatin
Trastuzumab
Pertuzumab
Trastuzumab emtansine
Sponsored by
About this trial
This is an interventional treatment trial for HER2-positive Breast Cancer focused on measuring HER2-positive Breast Cancer, De-escalation
Eligibility Criteria
Inclusion Criteria:
- Women ≥18 years of age
- Biopsy proven HER2+ early breast cancer
- ECOG performance status 0-1
- Should be a candidate for neoadjuvant chemotherapy using standard guidelines of tumor size of 2cm or more and /or axillary lymph node-positive disease.
- Adequate cardiac, bone marrow, kidney, and liver functions per treating physician's discretion.
- Women of childbearing potential who are sexually active must agree to use highly effective methods of contraception during treatment and for three weeks after the last dose of chemotherapy or anti-HER2 therapy. The women currently using hormonal contraceptives must agree to change to an alternative highly effective method of contraception
- Willingness and ability to comply with study and follow-up procedures and give written informed consent.
Exclusion Criteria:
- Any evidence of stage IV breast cancer
- Participant deemed unsuitable for clinical trial enrolment by treating physician based on the participants' compliance, location and commute requirements, or tolerance of therapies involved
- Any invasive malignancy within the last two years of study enrollment except for adequately treated basal cell carcinoma, squamous cell carcinoma, or non-melanoma skin cancer.
- Women who are pregnant or breastfeeding.
Sites / Locations
- University of Rochester Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Pathologic complete response (pCR)
Residual Disease
Arm Description
Participants will receive four cycles of TCHP [docetaxel (Taxotere®), carboplatin, trastuzumab (Herceptin®), pertuzumab], followed by surgery. Participants who achieve pathologic complete response will receive infusions of trastuzumab every 3 weeks for a total of 12 cycles/infusions.
Participants will receive four cycles of TCHP [docetaxel (Taxotere®, carboplatin, trastuzumab (Herceptin®), pertuzumab], followed by surgery. Participants who have residual disease may be offered two more cycles of TCHP in the adjuvant settings (optional) per treating oncologist's discretion and then will receive infusion of Trastuzumab Emtansine (TDM1) plus pertuzumab every three weeks for a total of 12 cycles/infusions.
Outcomes
Primary Outcome Measures
One Year Invasive Disease-Free Survival
The study will be considered feasible if the researchers observe the invasive disease free survival (IDFS) estimate at one year to be 90% or more among those who achieved a pCR, or if the researchers observe the IDFS estimate at one year to be 85% or more among those who had residual disease.
Secondary Outcome Measures
Pathologic Complete Response rate
Assess the pCR rate after four cycles (12 weeks) of TCHP.
Toxicity of chemo and HER2 therapies
Evaluate toxicity associated with neoadjuvant and adjuvant chemo and/or HER2 directed therapies. Percentage of grade 1 to grade 5 toxicities will be assessed during the neo-adjuvant TCHP therapy for all participants. Percentage of grade 1 to grade 5 toxicities will be assessed with adjuvant trastuzumab therapy for the cohort with pathological complete response, and with optional adjuvant TCHP therapy and adjuvant TDM1 + pertuzumab therapy for the residual disease cohort. Toxicity data will be obtained based on the clinical assessment of the participants by the investigators and based on laboratory data.
Two Year Invasive Disease-Free Survival
Two year invasive disease-free survival (IDFS) of participants with pCR and participants with residual disease
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04419181
Brief Title
Feasibility of Chemotherapy De-escalation in Early-Stage HER2 Positive Breast Cancer
Official Title
A Feasibility Study of De-escalation of Chemotherapy in Patients With Early-Stage HER2 Positive Breast Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Suspended
Why Stopped
Change in the landscape of current treatment of early stage breast cancer. Larger clinical trials answering similar questions are expected to result in the next few years.
Study Start Date
August 11, 2024 (Anticipated)
Primary Completion Date
June 1, 2025 (Anticipated)
Study Completion Date
June 1, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Rochester
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The main purpose of this research study is to find out if de-escalation of chemotherapy before surgery followed by a selective escalation of adjuvant targeted therapies are efficacious and tolerable in early-stage HER2 positive breast cancer.
Detailed Description
Assess the feasibility of four cycles of neoadjuvant Docetaxel Carboplatin Trastuzumab and Pertuzumab (TCHP) in women with early-stage (local/locally advanced) HER2+ breast cancer with a selective escalation of targeted HER2 directed therapy in the high risk group in the adjuvant setting. Participants with any residual disease after four cycles of TCHP will receive Trastuzumab Emtansine (TDM1) plus Pertuzumab while those with complete pathological response will receive Trastuzumab in the adjuvant settings.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HER2-positive Breast Cancer
Keywords
HER2-positive Breast Cancer, De-escalation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Participants will be assigned to an arm of the trial based on their outcomes after surgery.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Pathologic complete response (pCR)
Arm Type
Experimental
Arm Description
Participants will receive four cycles of TCHP [docetaxel (Taxotere®), carboplatin, trastuzumab (Herceptin®), pertuzumab], followed by surgery. Participants who achieve pathologic complete response will receive infusions of trastuzumab every 3 weeks for a total of 12 cycles/infusions.
Arm Title
Residual Disease
Arm Type
Experimental
Arm Description
Participants will receive four cycles of TCHP [docetaxel (Taxotere®, carboplatin, trastuzumab (Herceptin®), pertuzumab], followed by surgery. Participants who have residual disease may be offered two more cycles of TCHP in the adjuvant settings (optional) per treating oncologist's discretion and then will receive infusion of Trastuzumab Emtansine (TDM1) plus pertuzumab every three weeks for a total of 12 cycles/infusions.
Intervention Type
Drug
Intervention Name(s)
Docetaxel
Other Intervention Name(s)
Taxotere
Intervention Description
Dose: 75 mg/m2 q3w
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Other Intervention Name(s)
Paraplatin
Intervention Description
Dose: area under the concentration-time curve [AUC] 6 q3w
Intervention Type
Drug
Intervention Name(s)
Trastuzumab
Other Intervention Name(s)
Herceptin
Intervention Description
Dose: 8-mg/kg loading dose, 6-mg/kg maintenance dose q3w
Intervention Type
Drug
Intervention Name(s)
Pertuzumab
Other Intervention Name(s)
Perjeta
Intervention Description
Dose: 840-mg loading dose, 420-mg maintenance dose q3w
Intervention Type
Drug
Intervention Name(s)
Trastuzumab emtansine
Other Intervention Name(s)
TDM1
Intervention Description
Dose: 3.6mg/kg q3w
Primary Outcome Measure Information:
Title
One Year Invasive Disease-Free Survival
Description
The study will be considered feasible if the researchers observe the invasive disease free survival (IDFS) estimate at one year to be 90% or more among those who achieved a pCR, or if the researchers observe the IDFS estimate at one year to be 85% or more among those who had residual disease.
Time Frame
One year from the breast cancer surgery
Secondary Outcome Measure Information:
Title
Pathologic Complete Response rate
Description
Assess the pCR rate after four cycles (12 weeks) of TCHP.
Time Frame
12 weeks from start of treatment
Title
Toxicity of chemo and HER2 therapies
Description
Evaluate toxicity associated with neoadjuvant and adjuvant chemo and/or HER2 directed therapies. Percentage of grade 1 to grade 5 toxicities will be assessed during the neo-adjuvant TCHP therapy for all participants. Percentage of grade 1 to grade 5 toxicities will be assessed with adjuvant trastuzumab therapy for the cohort with pathological complete response, and with optional adjuvant TCHP therapy and adjuvant TDM1 + pertuzumab therapy for the residual disease cohort. Toxicity data will be obtained based on the clinical assessment of the participants by the investigators and based on laboratory data.
Time Frame
One year from the start of treatment
Title
Two Year Invasive Disease-Free Survival
Description
Two year invasive disease-free survival (IDFS) of participants with pCR and participants with residual disease
Time Frame
Two years from the breast cancer surgery
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Women ≥18 years of age
Biopsy proven HER2+ early breast cancer
ECOG performance status 0-1
Should be a candidate for neoadjuvant chemotherapy using standard guidelines of tumor size of 2cm or more and /or axillary lymph node-positive disease.
Adequate cardiac, bone marrow, kidney, and liver functions per treating physician's discretion.
Women of childbearing potential who are sexually active must agree to use highly effective methods of contraception during treatment and for three weeks after the last dose of chemotherapy or anti-HER2 therapy. The women currently using hormonal contraceptives must agree to change to an alternative highly effective method of contraception
Willingness and ability to comply with study and follow-up procedures and give written informed consent.
Exclusion Criteria:
Any evidence of stage IV breast cancer
Participant deemed unsuitable for clinical trial enrolment by treating physician based on the participants' compliance, location and commute requirements, or tolerance of therapies involved
Any invasive malignancy within the last two years of study enrollment except for adequately treated basal cell carcinoma, squamous cell carcinoma, or non-melanoma skin cancer.
Women who are pregnant or breastfeeding.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ajay Dhakal, MBBS
Organizational Affiliation
University of Rochester
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Rochester Medical Center
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Feasibility of Chemotherapy De-escalation in Early-Stage HER2 Positive Breast Cancer
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