Omission of Surgery and Sentinel Lymph Node Dissection in Clinically Low-risk HER2positive Breast Cancer With High HER2 Addiction and a Complete Response Following Standard Anti- HER2-based Neoadjuvant Therapy (ELPIS Trial)

NCT04301375 | Not Yet Recruiting Phase 2

• 1 other identifier: 2019-004559-35
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, single arm, open-label, exploratory study in women with primary operable HER2-positive, HER2-enriched(HER2-E)/ERBB2-high breast cancer according to PAM50 intrinsic subtype and a ERBB2 pre-defined cutoff (high vs low ERBB2 expression), to evaluate the omission of surgery and sentinel lymph node dissection in patients with HER2-E and ERBB2 high breast cancer who achieving a complete response following standard anti-HER2-based neoadjuvant therapy with paclitaxel/trastuzumab/pertuzumab.

Conditions

Mammary Cancer

Outcome Measures

Primary Outcomes (1)

• To estimate the loco-regional invasive disease-free survival of patients who achieve a complete response

  To estimate the loco-regional invasive disease-free survival at 3-year of patients who achieve a complete response based on imaging and a stereotactic-guided vacuum-assisted breast biopsy, and omit loco-regional surgery. 3-years loco-regional invasive disease-free survival rate is defined as time from the first date of no disease (i.e., date of stereotaxic guided biopsy) to loco-regional recurrence. Loco-regional recurrence is defined as recurrence of breast cancer in the same breast parenchyma as the original primary lesion, the axilla, regional lymph nodes, chest wall and/or skin of the ipsilateral breast.

  3 years

Secondary Outcomes (7)

• To estimate the disease-free survival at 3years of patients who achieve a complete response based on imaging and a stereotaxic guided biopsy and omit loco-regional surgery following neoadjuvant chemotherapy and dual HER2 blockade.

  3 years

• To estimate the disease-free survival at 5 years of patients who achieve a complete response based on imaging and a stereotaxic guided biopsy and omit loco-regional surgery following neoadjuvant chemotherapy and dual HER2 blockade.

  5 years

• To estimate the disease-free survival at 3years of patients who do not achieve a complete response based on imaging following neoadjuvant chemotherapy and dual HER2 blockade

  3 years

• To estimate the disease-free survival at 5 years of patients who do not achieve a complete response based on imaging following neoadjuvant chemotherapy and dual HER2 blockade

  5 years

• To compare the cost in patients with and without breast cancer surgery, not only direct cost for hospitals/public health system, but also indirect cost for public system

  5 years

Study Arms (1)

Study treatment

EXPERIMENTAL

Drug: Pertuzumab and trastuzumab FDC subcutaneous; Drug: Paclitaxel; Drug: TDM1; Drug: Endocrine therapy; Procedure: Omission surgery

Interventions

Pertuzumab and trastuzumab FDC subcutaneous DRUG

Pertuzumab and trastuzumab FDC subcutaneous, A loading dose of 1200 mg pertuzumab and 600 mg trastuzumab followed by a maintenance dose of 600 mg pertuzumab and 600 mg; day 1 of each 3 week cycle during 5 neoadjuvant cycles and 13 adjuvant cycles if complete response

Study treatment

Paclitaxel DRUG

80 mg/m2, day 1,8,15 of each 3 week cycle during 4 cycles

Study treatment

TDM1 DRUG

3,6 mg/kg, 14 adjuvant cycles if not complete response

Study treatment

Endocrine therapy DRUG

Adjuvant endocrine therapy will be administered as per local practice and according to recognized clinical practice guidelines

Study treatment

Omission surgery PROCEDURE

Omission of surgery and sentinel lymph node dissection in patients with HER2-E and ERBB2 high breast cancer who achieving a complete response following standard anti-HER2-based neoadjuvant therapy with paclitaxel/trastuzumab/pertuzumab

Study treatment

Eligibility Criteria

• Age: 40 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female participants who are at least 40 years of age on the day of signing the informed consent form with histologically confirmed diagnosis of breast cancer.
• A participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential as defined in protocol OR
• A woman of childbearing potential who agrees to follow the contraceptive guidance in protocol during the treatment period and for at least 7 months after the last dose of study treatment
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
• Histologically confirmed invasive adenocarcinoma of the breast, with all of the following characteristics:
• HER2-positive status by local determination according to 2018 American Society of Clinical Oncology //College of American Pathologists guidelines.
• PAM50 HER2-enriched subtype and ERBB2-high as predefined cutoff as per central determination.
• Unifocal invasive carcinoma: only 1 invasive focus can be observed (the tumor focus containing or not containing an in situ component)
• Tumor largest diameter ≤2 cm as defined by breast Magnetic resonance imaging.
• No nodal involvement (i.e. cN0). Any suspicious axillary node by ultrasound must be biopsied. If the biopsy or the fine-needle aspiration is negative of tumor cells, patient is eligible.
• No evidence of distant metastasis (M0) by routine clinical assessment.
• Patient must have known estrogen receptor and progesterone receptor status locally determined prior to study entry
• Eligible for taxane therapy
• Willingness of the patient to omit surgery if all criteria are met following neoadjuvant therapy

You may not qualify if:

• A woman of childbearing potential who has a positive urine pregnancy test within 72 hours prior to allocation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Has received prior anti-cancer therapy, including investigational agents, or treatment for primary invasive breast cancer.
• Known hypersensitivity to any of the excipients of trastuzumab, pertuzumab, TDM1 or paclitaxel.
• Clinical stage II, III or IV
• History of radiotherapy in the ipsilateral breast or axilla
• History of surgery of the ipsilateral axilla
• Bilateral invasive breast cancer
• Infiltrating lobular carcinoma.
• Multicentric or multifocal breast cancer, defined as the presence of two or more foci of cancer in the same or different quadrants of the same breast.
• Patients who have undergone sentinel lymph node biopsy prior to study treatment.
• Patient has active cardiac disease or a history of cardiac dysfunction including any of the following:
• History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty or stenting) or symptomatic pericarditis within 12 months prior to screening.
• History of documented congestive heart failure (New York Heart Association functional classification III-IV).
• Documented cardiomyopathy.
• Patient has a Left Ventricular Ejection Fraction \< 55% at baseline as determined by Multiple Gated acquisition scan or echocardiogram.

Sponsors & Collaborators

• David Garcia Cinca: lead
• Fundacion Clinic per a la Recerca Biomédica: collaborator

Study Sites (1)

Hospital Clínic de Barcelona

Barcelona, 08036, Spain

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

pertuzumab; Paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Central Study Contacts

Nuria Chic, MD

CONTACT

CHIC@clinic.cat

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Trial Manager

Study Record Dates

• First Submitted: February 14, 2020
• First Posted: March 10, 2020
• Study Start: June 15, 2020
• Primary Completion (Estimated): July 15, 2027
• Study Completion (Estimated): July 15, 2027
• Last Updated: March 10, 2020

Record last verified: 2020-03

Locations

ES (1)