An Open Label Study of Postmenopausal Women With Oestrogen Receptor Positive Locally Advanced or Metastatic Breast Cancer Treated With Everolimus (RAD001) With Exemestane, With Exploratory Epigenetic Marker Analysis

NCT01743560 | Completed Phase 4 Results

• 2 other identifiers: CRAD001YGB112012-003689-41
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 11

Brief Summary

Determine the overall response rate (ORR) at 48 weeks to everolimus (RAD001, 10mg daily p.o.) and exemestane (25mg daily p.o.) treatment in postmenopausal women with oestrogen receptor positive breast cancer who have previous experienced recurrence or progression on non-steroidal aromatase inhibitor (NSAI) therapy.

Conditions

Oestrogen Receptor Positive Advanced Breast Cancer

Keywords

Breast Neoplasms; Neoplasms; Breast diseases; Skin diseases; Exemestane; Antibiotics, Antineoplastic; Everolimus; Antineoplastic Agents; Therapeutic Uses; Pharmacologic Actions; Immunosuppressive Agents; Physiological Effects of Drugs; Aromatase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action

Outcome Measures

Primary Outcomes (2)

• Best Overall Response of Everolimus and Exemestane Treatment in Postmenopausal Women With Hormone Receptor Positive Locally Advanced or Metastatic Breast Cancer

  The best Overall Response (OR) for each patient is determined from the sequence of investigator overall lesion responses according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1.). To be assigned a best OR of Complete Responese (CR) at least two determinations of CR at least 4 weeks apart before progression are required. To be assigned a best OR of Partial Response (PR) at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) are required.The Overall Response Rate (ORR) was defined as the proportion of patients with a best OR of confirmed CR or PR by week 48.

  At 48 weeks

• Overall Response Rate of Everolimus and Exemestane Treatment in Postmenopausal Women With Hormone Receptor Positive Locally Advanced or Metastatic Breast Cancer

  The Overall Response Rate (ORR) was defined as the proportion of patients with a best OR of confirmed CR or PR by week 48. Treatment success is defined as: The best Overall Response (OR) for each patient is determined from the sequence of investigator overall lesion responses according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1.). To be assigned a best OR of Complete Responese (CR) at least two determinations of CR at least 4 weeks apart before progression are required. To be assigned a best OR of Partial Response (PR) at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) are required.

  At 48 weeks

Secondary Outcomes (8)

• Progression-free Survival (PFS) Events as Per Investigators - FAS

  Start of treatment to the date of event defined as first documented progression due to any cause up to approximately 48 weeks

• Progression-free Survival (PFS) by Median Time in Weeks as Per Investigators - FAS

  Start of treatment to the date of event defined as first documented progression due to any cause up to approximately 48 weeks

• Progression-free Survival (PFS) - % Event-free Probability Estimate - FAS

  Start of treatment to the date of event defined as first documented progression due to any cause up to approximately 48 weeks

• Overall Survival (OS) Events (Number of Deaths) - FAS

  Start of treatment to the date of death up to approximately 48 weeks

• Overall Survival (OS) - % Event-free Probability Estimate - FAS

  Start of treatment to the date of death up to approximately 48 weeks

Study Arms (1)

Everolimus and Exemestane

EXPERIMENTAL

Postmenopausal women diagnosed with oestrogen receptor positive locally advanced or metastatic breast cancer will receive RAD001 at a dose of 10mg daily p.o. and exemestane 25mg daily p.o. for 48 weeks.

Drug: RAD001; Drug: Exemestane

Interventions

RAD001 DRUG

All postmenopausal women with oestrogen receptor positive locally advanced or metastatic breast cancer were treated with oral tablet RAD001 at a dose of 10mg daily and oral tablet exemestane 25mg daily. The study treatment for an individual patient was to begin on Study Day 1 and continue until the last patient enrolled completed the study at day 336 or until disease progression; unacceptable toxicity, death or early discontinuation from the study for any other reason, whichever occurs first.

Also known as: Everolimus

Everolimus and Exemestane

Exemestane DRUG

All postmenopausal women with oestrogen receptor positive locally advanced or metastatic breast cancer were to be treated with oral tablet RAD001 at a dose of 10mg daily and oral tablet exemestane 25mg daily. The study treatment for an individual patient was to begin on Study Day 1 and continue until the last patient enrolled completed the study at day 336 or until disease progression; unacceptable toxicity, death or early discontinuation from the study for any other reason, whichever occurs first.

Everolimus and Exemestane

Eligibility Criteria

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

You may qualify if:

• Histological or cytological confirmation of oestrogen receptor positive (ER+) and/or progesterone receptor positive (PgR+), human epidermal growth factor receptor 2 (HER2) negative breast cancer.
• Availability of archival tumour tissue (the tissue block or slides will be sent to the central laboratory for analysis).
• Postmenopausal women. The investigator must confirm postmenopausal status. Postmenopausal status is defined either by:
• Age ≥ 55 years and one year or more of amenorrhea
• Age \< 55 years and one year or more of amenorrhea and postmenopausal levels of FSH and LH per local institutional standards
• Prior hysterectomy and has postmenopausal levels of Follicle stimulating hormone (FSH) and Luteinizing Hormone (LH) per local institutional standards Surgical menopause with bilateral oophorectomy
• Disease progression following prior therapy with NSAI, defined as:
• Recurrence while on or after completion of an adjuvant treatment including letrozole or anastrozole, or
• Progression while on or following the completion of letrozole or anastrozole treatment for locally advanced or metastatic breast cancer
• Note: Non-steroidal aromatase inhibitors (i.e. letrozole or anastrozole) do not have to be the last treatment prior to enrollment. Other prior anticancer therapy, e.g. tamoxifen, fulvestrant, exemestane are also allowed. Patients must have recovered to grade 1 or better from any adverse events (except alopecia) related to previous therapy prior to enrollment.
• \- Radiological evidence of recurrence or progression on last systemic therapy prior to enrollment.
• Patients must have:
• At least one lesion that can be accurately measured or
• Bone lesions: lytic or mixed (lytic + sclerotic) in the absence of measurable disease
• \- Adequate bone marrow and coagulation function as shown by:

You may not qualify if:

• HER2-overexpressing patients by local laboratory testing (IHC 3+ staining or in situ hybridization positive).
• Pre-menopausal, pregnant, lactating women.
• Known hypersensitivity to mammilian target of Rapamycin (mTOR) inhibitors, e.g. sirolimus (rapamycin) or to their excipients.
• Known hypersensitivity to exemestane, to the active substance or to any of the excipients.
• Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose galactose malabsorption.
• Radiotherapy within four weeks prior to enrollment except in case of localized radiotherapy for analgesic purpose or for lytic lesions at risk of fracture which can then be completed within two weeks prior to enrollment. Patients must have recovered from radiotherapy toxicities prior to enrollment.
• Currently receiving hormone replacement therapy, unless discontinued prior to enrollment.
• Patients receiving concomitant immunosuppressive agents or chronic corticosteroids use, at the time of study entry except in cases outlined below:
• Prolonged systemic corticosteroid treatment during study, except for topical applications (e.g. rash),inhaled sprays (e.g. obstructive airways diseases), eye drops or local injections (e.g. intra-articular) should not be given. However:
• short duration (\<2 weeks) of systemic corticosteroids is allowed (e.g. chronic obstructive pulmonary disease, anti-emetic)
• low doses of corticosteroids for brain metastasis treatment is allowed
• Patients with symptomatic visceral metastasis (e.g. significant dyspnoea related to pulmonary lymphangitic carcinomatosis and lung metastases or clinically meaningful symptomatic liver metastasis)
• Symptomatic brain or other Central Nervous system (CNS) metastases.
• Active, bleeding diathesis, or on oral anti-vitamin K medication (except low dose warfarin, low molecular weight heparin (LMWH) and acetylsalicylic acid or equivalent, as long as the INR is 2.0)
• Any severe and / or uncontrolled medical conditions such as:

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (11)

Novartis Investigative Site

Epping, Essex, CM16 6TN, United Kingdom

Location

Novartis Investigative Site

Inverness, Invernesshire, IV2 3RE, United Kingdom

Location

Novartis Investigative Site

Ipswich, Suffolk, IP4 5PD, United Kingdom

Location

Novartis Investigative Site

Sutton, Surrey, SM2 5PT, United Kingdom

Location

Novartis Investigative Site

Cardiff, CF14 2TL, United Kingdom

Location

Novartis Investigative Site

Denbighshire, LL18 5UJ, United Kingdom

Location

Novartis Investigative Site

East Kilbride, G75 8RG, United Kingdom

Location

Novartis Investigative Site

East Yorkshire, HU16 5JQ, United Kingdom

Location

Novartis Investigative Site

Edinburgh, EH4 2XU, United Kingdom

Location

Novartis Investigative Site

London, SW3 6JJ, United Kingdom

Location

Novartis Investigative Site

Portsmouth, PO6 3LY, United Kingdom

Location

MeSH Terms

Conditions

Breast Neoplasms; Neoplasms; Breast Diseases; Skin Diseases

Interventions

Everolimus; exemestane

Condition Hierarchy (Ancestors)

Neoplasms by Site; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 24, 2012
• First Posted: December 6, 2012
• Study Start: January 31, 2013
• Primary Completion: August 15, 2016
• Study Completion: August 15, 2016
• Last Updated: July 18, 2019
• Results First Posted: April 1, 2019

Record last verified: 2019-07

Locations

GB (11)