Markers to Evaluate the Efficacy of PH-based Regimen as a Neoadjuvant Therapy for Operable HER2 Positive Breast Cancer (PHC-BC)

Gene Expression Assays and 68 Ga-Affibody HER-2 Imaging PET in Predicting Response to Treatment With Trastuzumab and Pertuzumab Before Surgery in Chinese Patients With HER2 Positive Breast Cancer

This study is to explore the markers in early prediction of the efficacy of pre-operative pertuzumab plus trastuzumab (PH) combined with chemotherapy for early stage or locally advanced human epidermal growth factor receptor-2 (HER-2) positive primary breast cancer.

Study Overview

• Status: Recruiting
• Conditions: HER2-positive Breast Cancer
• Intervention / Treatment: Diagnostic test: TCHP

Detailed Description

This study is to evaluate the correlation between early changes in multiple markers and pathological complete response in breast and lyphm nodes (tpCR) in patients with HER2-positive breast cancer receiving carboplatin, docetaxel and trastuzumab plus pertuzumab (TCHP) pre-operatively. The markers would be examined by gene expression assays, fluorodeoxyglucose positron emission tomography (18F-FDG-PET), 68 Ga-Affibody HER-2 Imaging PET, and organoid drug sensitivity test. Approximately 94 patients were treated with PH-based neoadjuvant therapy followed by surgery, and would complete 1 year of PH-based regimen in the adjuvant setting. The primary endpoint is the percent change of SUVmax from baseline to Day 15 (after the first cycle of anti HER-2 targeting drug treatment) on FDG PET and HER-2 imagining PET in correlation with pathological complete response (pCR) in patients treated with preoperative pertuzumab and trastuzumab. pCR was defined as no viable invasive cancer in breast and axilla by local pathology review.

• Study Type: Interventional
• Enrollment (Anticipated): 94
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200000
      • Recruiting
      • Shanghai Cancer Center, Fudan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Female or male, presenting for the first time with operable breast cancer, who had not received any previous treatment for an invasive malignancy.
2. Primary tumor greater than (>) 2 cm in diameter.
3. Age ≥ 18 years and < 70 years.
4. Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to (</=) 1.
5. Baseline left ventricular ejection fraction (LVEF) greater than or equal to (>/=) 55%
6. Availability of tumor tissue specimen after surgery.
7. Participants agree to undergo a core needle biopsy for genomic testing and organoid drug sensitivity assay.
8. Histologically proven diagnosis of breast cancer.
9. Patients have HER2-positive disease. HER2-positive disease was defined as follows: disease which overexpresses HER-2 by immunohistochemistry (IHC) 3+ and/or has HER2 amplification according to fluorescence in situ hybridization (FISH).
10. Had hormonal receptors (ER and PgR) assessed.
11. Signed informed consent.
12. Able to comply with the protocol.

Exclusion Criteria:

1. Metastatic disease (Stage IV) or bilateral breast cancer.
2. Any previous systemic therapy (including chemotherapy, immunotherapy, HER2 targeted agents, and antitumor vaccines) for cancer, or radiation therapy for cancer.
3. Prior breast or non-breast malignancy within 5 years prior to study entry.
4. Inadequate bone marrow, renal, or liver function
5. History or evidence of cardiovascular condition
6. Severe, uncontrolled systemic disease
7. Participants with poorly controlled diabetes or with evidence of clinically significant diabetic vascular complications.
8. Pregnancy or breast-feeding women.
9. Participants who received any investigational treatment within 4 weeks of study start.
10. Participants with known infection with human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus.
11. Current chronic daily treatment with corticosteroids (dose >10 mg methylprednisolone or equivalent [excluding inhaled steroids]).
12. Known hypersensitivity to any of the study drugs or excipients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: TCHP; Neoadjuvant Therapy (Cycles 1-7): Cycle 1: Pertuzumab (840mg loading dose, 420mg maintenance dose) + Trastuzumab (8mg/kg loading dose, 6-mg/kg maintenance dose) Cycle 2-7: Pertuzumab (840mg loading dose, 420mg maintenance dose) + Trastuzumab (8mg/kg loading dose, 6-mg/kg maintenance dose) + followed by carboplatin at target area under the plasma concentration-time curve (AUC) 6 and docetaxel at a starting dose of 75 mg/m2 then to 60mg/m2 (q3w). Adjuvant Therapy:patients would complete 1 year of PH-based regimen in the adjuvant setting. Patients are assessed by [18F]Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) and 68Ga-Affibody HER-2 Imaging PET. Besides, the changes of biomarkers would be examined by gene sequencing and organoid drug sensitivity test.

Diagnostic test: TCHP; Drug: Trastuzumab 8 mg/kg loading dose, then 6 mg/kg every 3 weeks, IV Other Name: Herceptin Drug: Pertuzumab 840 mg as a loading dose, then 420 mg every 3 weeks, IV Other Name: Perjeta Drug: carboplatin at target area under the plasma concentration-time curve (AUC) 6 Drug: docetaxel at a starting dose of 75 mg/m2 then to 60mg/m2 (q3w). All study drugs were administered intravenously. Procedure: 18-FDG-PET and 68 Ga-Affibody HER-2 Imaging PET will be performed at baseline, on day 15 and before surgery Genomic alterations (mutations/somatic rearrangements) are detected at baseline, on day 15 and before surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Standardized Uptake Value (SUV) on Positron Emission Tomography and Change in Gene Expression With Response	Change in SUVmax from baseline to Day 15 on 18-FDG PET and 68Ga-Affibody HER-2 Imaging PET in correlation with pathological complete response (pCR) in patients treated with preoperative pertuzumab/trastuzumab.	From baseline to day 15

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathologic complete response in the breast and lymph nodes (ypT0/Tis ypN0)	To determine whether the composite markers can predict pathologic complete response in the breast and lymph nodes in HER-2 positive breast cancer with PH combination with chemotherapy adjuvant therapy. Defined as the absence of any invasive component in the resected breast specimen and all resected lymph nodes following completion of neoadjuvant therapy (ypT0/Tis ypN0).	Immediately after the surgery
Invasive disease-free survival (iDFS) (excluding Second Primary Non-Breast Cancer [SPNBC])	To determine the correlation between the composite markers and invasive disease free survival in HER-2 positive breast cancer patients receiving docetaxel, carboplatin, and trastuzumab plus pertuzumab pre-operatively. iDFS event was defined as the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence; ipsilateral local-regional invasive breast cancer recurrence; distant recurrence; death attributable to any cause; contralateral invasive breast cancer. All SPNBCs and in situ carcinomas (including ductal carcinoma in situ [DCIS] and lobular carcinoma in situ [LCIS]) and non-melanoma skin cancer were excluded as an event.	Following surgery until Year 5
iDFS (including SPNBC)	The iDFS event was defined as the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence; ipsilateral local-regional invasive breast cancer recurrence; distant recurrence; death attributable to any cause; contralateral invasive breast cancer; SPNBC (with the exception of non-melanoma skin cancers and in situ carcinoma of any site).	Following surgery until Year 5
Overall survival (OS)	To determine the correlation between the composite markers and overall survival in HER-2 positive breast cancer patients receiving docetaxel, carboplatin, and trastuzumab plus pertuzumab pre-operatively. Percentage of participants who died due to any cause is reported.	Following surgery until Year 5

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): April 21, 2020
• Primary Completion (Anticipated): April 30, 2025
• Study Completion (Anticipated): April 30, 2030

Study Registration Dates

• First Submitted: February 12, 2020
• First Submitted That Met QC Criteria: February 21, 2020
• First Posted (Actual): February 24, 2020

Study Record Updates

• Last Update Posted (Actual): May 4, 2020
• Last Update Submitted That Met QC Criteria: April 30, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: SCHBCC-NO28

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No