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

Phase 3

Not yet recruiting

• Conditions: HER2-positive Breast Cancer
• Interventions: Drug: Paclitaxel + Trastuzumab; Drug: Trastuzumab

• Registration Number: NCT05388500
• Lead Sponsor: Institut de cancérologie Strasbourg Europe

Brief Summary

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.

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 Timeline

• Status Verified: 2022-05
• Study First Submitted: 2022-05-12
• Study First Submitted QC: 2022-05-18
• Study First Posted: 2022-05-24
• Last Update Submitted: 2022-05-24
• Last Update Posted: 2022-05-27
• Study Start: 2022-12-15
• Primary Completion: 2030-12-15
• Study Completion: 2030-12-15

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 800

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group A (Paclitaxel + Trastuzumab)	Paclitaxel + Trastuzumab	-
Group B (Trastuzumab)	Trastuzumab	-

Primary Outcome Measures

Name	Time	Method
Time to progression	up to 5 years	Time from the date of randomization to the date of progression

Secondary Outcome Measures

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