Protocol for Herceptin as Adjuvant Therapy With Reduced Exposure to Chemotherapy (PHARE-C) (PHARE-C)

Protocol for Herceptin as Adjuvant Therapy With Reduced Exposure to Chemotherapy, a Randomised Comparison of Trastuzumab vs Trastuzumab+Paclitaxel in Women With HER2-positive Early Breast Cancer Receiving Neoadjuvant Treatment

RATIONALE: According to previous results from PHARE study, a subgroup of patients with low-risk cancer (< 3 cm) without axillary lymph node involvement or small (< 2 cm) with minimal lymph node involvement (1 positive node) presented low risk of recurrence. Maintaining chemotherapy in this subgroup could cause toxicity and it is not yet known whether giving trastuzumab as monotherapy in neoadjuvant setting is as effective as giving trastuzumab combined with paclitaxel in patients with low risk early breast cancer.

PURPOSE: This randomized phase III trial is studying trastuzumab as monotherapy in neoadjuvant setting to see if this treatment regimen is as efficient compared to trastuzumab combination with paclitaxel chemotherapy in treating women with low risk (tumor size< 3 cm, N0) early breast cancer.

Study Overview

• Status: Not yet recruiting
• Conditions: HER2-positive Breast Cancer
• Intervention / Treatment: Drug: Paclitaxel + Trastuzumab; Drug: Trastuzumab

Detailed Description

PHARE-C is an open-label, randomized, phase III, non-inferiority trial, that will recruit patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer to allow for comparison of neoadjuvant treatment with paclitaxel plus trastuzumab versus trastuzumab as monotherapy.

Non-inferiority between the two treatment arms will be evaluated in terms of time to progression as primary objective. Treatment tolerance and cardiac toxicity will be assessed as secondary objectives.

In case of non pCR, a rescue by Trastuzumab emtansine (T-DM1) is planned to control the survival outcome.

• Study Type: Interventional
• Enrollment (Anticipated): 800
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Histologically confirmed adenocarcinoma of the breast, nonmetastatic disease and non operated tumor
• Without suspicious axillary nodes
• Tumor size < 30 mm
• Eligibility to receive a weekly paclitaxel based chemotherapy for this cancer
• Left Ventricular Ejection Fraction (LVEF) obtained and > 50% as measured by echocardiography (Simpson method) or multigated acquisition scan (MUGA) at 3 months (-/+ 1 month)

• Overexpression of HER-2 in the invasive component of the primary tumor as indicated by one of the following:

  3+ by immunohistochemistry (IHC) 2+ by IHC and confirmation by fluorescent in situ hybridization (FISH) or chromogenic in situ hybridization (CISH)

• With signed Informed consent

Exclusion Criteria:

• Previous anti-HER2 treatment (except for HERCEPTIN)
• Cardiac disease or other medical conditions preventing trastuzumab administration
• Known allergy to trastuzumab, murine proteins or other excipients
• Pregnant or breastfeeding women
• Patients that are not able to comply to the protocol assessments for geographic, social or psychological reasons

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group A (Paclitaxel + Trastuzumab)	Drug: Paclitaxel + Trastuzumab; Regarding neoadjuvant treatment : - 9 to 12 weeks of neoadjuvant treatment Trastuzumab IV (8mg/kg loading dose followed by 6 mg/kg maintenance dose) or SubCutaneous (SC) (600mg fixed dose) every 3 weeks + weekly Paclitaxel IV : 80 to 90 mg/m2 Regarding adjuvant treatment patients will receive one of the following anti-HER2 therapy following the current standard to complete 1 year of anti-HER2 therapy in total : in case of pCR : patient will receive trastuzumab; in case of non pCR : patients will receive trastuzumab emtansine (T-DM1)
Experimental: Group B (Trastuzumab)	Drug: Trastuzumab; Regarding neoadjuvant treatment : - 9 to 12 weeks of neoadjuvant treatment Trastuzumab IV (8mg/kg loading dose followed by 6 mg/kg maintenance dose) or SC (600mg fixed dose) every 3 weeks Regarding adjuvant treatment patients will receive one of the following anti-HER2 therapy following the current standard to complete 1 year of anti-HER2 therapy in total : in case of pCR : patient will receive trastuzumab; in case of non pCR : patients will receive trastuzumab emtansine (T-DM1)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to progression	Time from the date of randomization to the date of progression	up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival		up to 5 years
Cardiac toxicity	defined by Ventricular Ejection Fraction measure according to the technique used, clinical examination or any other appropriate exams	up to 5 years
Treatment toxicity	Adverse Event and Serious Adverse Event due to trastuzumab or paclitaxel graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0	up to 5 years
Total pathological Complete Response (tpCR)	Defined by complete absence of cancerous cells in breast, axillary lymph node chain and/or axillary sentinel lymph node (ypT0/is) in excised tissues	through surgery completion, an average of 12 weeks
Breast pathological Complete Response (bpCR)	Defined by complete absence of cancerous cells in breast (ypT0/is, ypN0) in excised tissues	through surgery completion, an average of 12 weeks
Distant metastasis Free Survival	Time from the date of randomization to the date of 1st metastasis	up to 5 years

Collaborators and Investigators

• Sponsor: Institut de cancérologie Strasbourg Europe
• Investigators: Study Chair: Xavier PIVOT, MD, PhD, Institut de cancérologie Strasbourg Europe

Study record dates

Study Major Dates

• Study Start (Anticipated): December 15, 2022
• Primary Completion (Anticipated): December 15, 2030
• Study Completion (Anticipated): December 15, 2030

Study Registration Dates

• First Submitted: May 12, 2022
• First Submitted That Met QC Criteria: May 18, 2022
• First Posted (Actual): May 24, 2022

Study Record Updates

• Last Update Posted (Actual): May 27, 2022
• Last Update Submitted That Met QC Criteria: May 24, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Paclitaxel; Trastuzumab
• Other Study ID Numbers: 2022-008

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No