Feasibility of Chemotherapy De-escalation in Early-Stage HER2 Positive Breast Cancer

Sponsor

University of Rochester (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04419181

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
HER2-positive Breast Cancer	Drug: Docetaxel Drug: Carboplatin Drug: Trastuzumab Drug: Pertuzumab Drug: Trastuzumab emtansine	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Participants will be assigned to an arm of the trial based on their outcomes after surgery.Participants will be assigned to an arm of the trial based on their outcomes after surgery.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Feasibility Study of De-escalation of Chemotherapy in Patients With Early-Stage HER2 Positive Breast Cancer

Anticipated Study Start Date :

Jun 1, 2022

Anticipated Primary Completion Date :

Jun 1, 2022

Anticipated Study Completion Date :

Jun 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pathologic complete response (pCR) 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.	Drug: Docetaxel Dose: 75 mg/m2 q3w Other Names: Taxotere Drug: Carboplatin Dose: area under the concentration-time curve [AUC] 6 q3w Other Names: Paraplatin Drug: Trastuzumab Dose: 8-mg/kg loading dose, 6-mg/kg maintenance dose q3w Other Names: Herceptin Drug: Pertuzumab Dose: 840-mg loading dose, 420-mg maintenance dose q3w Other Names: Perjeta
Experimental: Residual Disease 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.	Drug: Docetaxel Dose: 75 mg/m2 q3w Other Names: Taxotere Drug: Carboplatin Dose: area under the concentration-time curve [AUC] 6 q3w Other Names: Paraplatin Drug: Trastuzumab Dose: 8-mg/kg loading dose, 6-mg/kg maintenance dose q3w Other Names: Herceptin Drug: Pertuzumab Dose: 840-mg loading dose, 420-mg maintenance dose q3w Other Names: Perjeta Drug: Trastuzumab emtansine Dose: 3.6mg/kg q3w Other Names: TDM1

Arm

Intervention/Treatment

Experimental: Pathologic complete response (pCR)

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.

Drug: Docetaxel

Dose: 75 mg/m2 q3w

Other Names:

Taxotere

Drug: Carboplatin

Dose: area under the concentration-time curve [AUC] 6 q3w

Other Names:

Paraplatin

Drug: Trastuzumab

Dose: 8-mg/kg loading dose, 6-mg/kg maintenance dose q3w

Other Names:

Herceptin

Drug: Pertuzumab

Dose: 840-mg loading dose, 420-mg maintenance dose q3w

Other Names:

Perjeta

Experimental: Residual Disease

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.

Drug: Docetaxel

Dose: 75 mg/m2 q3w

Other Names:

Taxotere

Drug: Carboplatin

Dose: area under the concentration-time curve [AUC] 6 q3w

Other Names:

Paraplatin

Drug: Trastuzumab

Dose: 8-mg/kg loading dose, 6-mg/kg maintenance dose q3w

Other Names:

Herceptin

Drug: Pertuzumab

Dose: 840-mg loading dose, 420-mg maintenance dose q3w

Other Names:

Perjeta

Drug: Trastuzumab emtansine

Dose: 3.6mg/kg q3w

Other Names:

TDM1

Outcome Measures

Primary Outcome Measures

One Year Invasive Disease-Free Survival [One year from the breast cancer surgery]
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 [12 weeks from start of treatment]
Assess the pCR rate after four cycles (12 weeks) of TCHP.
Toxicity of chemo and HER2 therapies [One year from the start of treatment]
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 years from the breast cancer surgery]
Two year invasive disease-free survival (IDFS) of participants with pCR and participants with residual disease

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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.