Clinical trial NCT05388500: Protocol for Herceptin as Adjuvant Therapy With Reduced Exposure to Chemotherapy (PHARE-C)
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: HER2-positive Breast Cancer
Lead sponsor: Institut de cancérologie Strasbourg Europe
Sponsor class: OTHER
First posted: 2022-05-24
Enrollment: 800
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Time to progression
timeFrame: up to 5 years
Secondary outcomes:
measure: Cardiac toxicity
timeFrame: up to 5 years
measure: Treatment toxicity
timeFrame: up to 5 years
measure: Total pathological Complete Response (tpCR)
timeFrame: through surgery completion, an average of 12 weeks
measure: Breast pathological Complete Response (bpCR)
timeFrame: through surgery completion, an average of 12 weeks
measure: Distant metastasis Free Survival
timeFrame: up to 5 years
measure: Overall Survival
timeFrame: up to 5 years
Other outcomes:
Locations:
Study officials:
affiliation: Institut de cancérologie Strasbourg Europe
name: Xavier PIVOT, MD, PhD
role: STUDY_CHAIR
References: