Neoadj ph 2 AI Plus Everolimus in Postmenopausal Women w/ ER Pos/HER2 Neg, Low Risk Score

NCT02236572 | Terminated Phase 2 Results DMC

• 1 other identifier: 1405013982
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to see whether adding everolimus to hormone treatment before breast surgery will increase the chances of shrinking the breast cancer in those patients with hormone-responsive breast cancer and a lower Oncotype DX® Recurrence Score ( 25 or less), compared to prior experience with hormone therapy alone. Everolimus is a drug currently approved for use by the United States Food and Drug administration (FDA) for the treatment of patients with advanced or metastatic kidney or breast cancer. Everolimus is considered investigational for non-metastatic breast cancer patients.

Conditions

Breast Cancer

Keywords

Postmenopausal; ER-positive, PR-positive, HER2-negative; Low and intermediate risk

Outcome Measures

Primary Outcomes (1)

• Achievement of a PEPI Score of 0 Following Neoadjuvant Treatment With Everolimus and an Aromatase Inhibitor

  (PEPI) preoperative endocrine prognostic index. The total PEPI score assigned to each patient is the sum of the risk points derived from the pT stage, pN stage, Ki67 level, and estrogen receptor status of the surgical specimen. An HR in the range of 1-2 receives one risk point; a HR in the 2-2.5 range, two risk points; a HR greater than 2.5, three risk points. The total risk point score for each patient is the sum of all the risk points accumulated from the four factors in the model. A lower PEPI score indicates lower risk for recurrence. A score of 0 is lowest risk for recurrence.

  up to 26 weeks

Secondary Outcomes (2)

• PEPI Score

  up to 26 weeks

• Participant Ability to Tolerate Study Treatment With Minimal Side Effects

  Up to 26 weeks

Study Arms (1)

Aromatase Inhibitor plus Everolimus

EXPERIMENTAL

Aromatase inhibitor plus everolimus by mouth daily for 26 weeks

Drug: Everolimus

Interventions

Everolimus DRUG

Aromatase inhibitor plus everolimus by mouth daily for 26 weeks. All patients will begin treatment on Cycle 1 Day 1 with both the standard dose of one of the following 3 aromatase inhibitors ( physician's choice) plus everolimus 10 mg by mouth daily: * Anastrozole 1 mg * Letrozole 2.5 mg * Exemestane 25 mg

Aromatase Inhibitor plus Everolimus

Eligibility Criteria

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

You may qualify if:

• Patients must have a histologically confirmed diagnosis of hormone receptor positive, HER2 negative invasive breast carcinoma.
• Tumors must be estrogen and/or progesterone receptor positive according to ASCO/CAP 2010 guidelines as either ER or PR ≥ 1% positive nuclear staining by immunohistochemistry. Estrogen and/or progesterone receptor results by Oncotype Dx will not be accepted.
• Tumors must be HER2 negative as defined according to ASCO/CAP 2013, as HER2 0 - 1+ by IHC or non-amplified FISH or CISH. If HER2 IHC is 2+, FISH/CISH must be performed and must not be positive (must be a ratio of \< 2), but otherwise FISH/CISH is not required if IHC is 0 or 1+ by institutional standards.
• Patients must not have had prior ipsilateral breast-conserving surgery or total mastectomy and be eligible for neoadjuvant treatment.
• Clinical Stage II-IIIC (T2-4 N0-3 M0) by mammogram, ultrasound or MRI
• Baseline Oncotpye Dx recurrence score \< 25.
• Staging studies with a CT scan of the chest and abdomen and bone scan, or a PET/CT is required for clinical stage III, and are considered optional for stage II breast cancers.
• Patients with multifocal, multicentric and synchronous bilateral breast cancers are allowed:
• Multifocal disease is defined as more than one invasive cancer \< 2 cm from the largest lesion within the same breast quadrant.
• Multicentric disease is defined as more than one invasive cancer ≥ 2 cm from the largest lesion within the same breast quadrant or more than one lesion in different quadrants.
• Synchronous bilateral disease is defined as invasive breast cancer in both breasts, diagnosed within 30 days of each other.
• In patients with multicentric or bilateral invasive breast cancers, all sampled lesions must be hormone receptor-positive and HER2-negative. Any lesion measuring \> 1 cm must have an Oncotype Dx and the score must be \< 25. Lesions less than 1 cm in size are not required to have an Oncotype Dx. One lesion (typically the largest) should be designated as the target lesion for which clinical and radiographic response to the neoadjuvant therapy will be judged.
• Patients with a hormone receptor-positive, HER2-negative invasive cancer that meets study criteria may have ductal carcinoma in situ in another quadrant of the same breast or in the contralateral breast even if the DCIS is hormone receptor-negative.
• Patients must have adequate bone marrow function, as defined by peripheral granulocyte count of ≥ 1,500/mL, hemoglobin ≥ 9 g/dL and a platelet count ≥ 100,000/ mL within 28 days prior to registration.
• Patients must have adequate hepatic function obtained within 28 days prior to registration and documented by all of the following:

You may not qualify if:

• Patients must not have inflammatory breast cancer (T4d) and must not have metastatic breast cancer (Stage IV disease).
• Patients must not have prior exposure to mTOR inhibitors (e.g. rapamycin, everolimus, sirolimus, temsirolimus, deforolimus).
• Patients must not have prior treatment with any investigational drug within the preceding 28 days and must not be planning to receive any other investigational drug for the duration of the study.
• Patient may not have any impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of the drug (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection).
• Uncontrolled diabetes mellitus as defined by HbA1c \>8% within 28 days prior to registration despite adequate therapy.
• Patients who have any severe and/or uncontrolled cardiac disease within ≤ 6 months prior to start of everolimus, including: unstable angina pectoris, Symptomatic congestive heart failure of New York heart Association Class III or IV, myocardial infarction, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease
• Patients must not have an organ allograft or other history of immune compromise.
• Patients must not be receiving chronic, systemic treatment with corticosteroids or other immunosuppressive agent. Topical or inhaled corticosteroids are allowed.
• Patients must not have a known history of HIV seropositivity
• Patients must not have a known diagnosis of hepatitis B or C. Patients with the following risk factors must have hepatitis screening pre-treatment:
• Blood transfusions prior to 1990
• Current or prior IV drug users
• Current or prior dialysis
• Household contact with a hepatitis B or C patient
• Current or prior high-risk sexual activity

Sponsors & Collaborators

• Yale University: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

Yale University

New Haven, Connecticut, 06520, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Everolimus

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Lajos Pusztai, MD, DPhil
• Organization: Yale Cancer Center

lajos.pusztai@yale.edu

(203) 200-2328

Study Officials

• Lajos Pusztai, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2014
• First Posted: September 10, 2014
• Study Start: November 29, 2014
• Primary Completion: March 1, 2021
• Study Completion: March 1, 2021
• Last Updated: February 1, 2022
• Results First Posted: February 1, 2022

Record last verified: 2022-01

Locations

US (1)