A clinical study of EVERolimus (RAD001)in combination with EXemestane in post-menopausal women with EStrogen receptor positive, human epidermal growth factor receptor 2 negative locally advanced or metastatic breast cancer

• Register: CTRI
• Last refreshed on: 24 November 2021
• Main ID: CTRI/2014/03/004443
• Date of registration: 05-03-2014
• Prospective Registration: Yes
• Primary sponsor: Novartis Healthcare Pvt Ltd
• Public title: A clinical study of EVERolimus (RAD001)in combination with EXemestane in post-menopausal women with EStrogen receptor positive, human epidermal growth factor receptor 2 negative locally advanced or metastatic breast cancer
• Scientific title: A phase IIIb, multi-center, open-label, expanded access study of EVERolimus (RAD001)in combination with EXemestane in post-menopausal women with EStrogen receptor positive, human epidermal growth factor receptor 2 negative locally advanced or metastatic breast cancer - EVEREXES
• Date of first enrolment: 07-03-2014
• Target sample size: 400
• Recruitment status: Closed to Recruitment of Participants
• URL: http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=6521
• Study type: Interventional
• Study design: Single Arm Trial; Method of generating randomization sequence:Not Applicable Method of allocation concealment:Not Applicable Blinding and masking:Open Label
• Phase: Phase 3/ Phase 4

Countries of recruitment

Algeria, Australia, Egypt, India, Indonesia, Jordan, Malaysia, Morocco, Oman, Republic of Korea, South Africa, Taiwan, Thailand, Tunisia, Turkey, Viet Nam

Contacts

• Name: Dr Manish Mistry
• Affiliation: Novartis India Ltd.

• Name: Dr Manish Mistry
• Affiliation: Novartis India Ltd.

Key inclusion & exclusion criteria

Inclusion criteria: 1. Adult women (greater than or equal to 18 years of age) with metastatic, recurrent or locally advanced breast cancer not amenable to curative treatment by surgery or radiotherapy.

2. Histological or cytological confirmation of estrogen receptor positive (ER positive) breast cancer.

3. Postmenopausal women. Ovarian radiation or treatment with a luteinizing hormonereleasing

hormone (LHRH) agonist (goserelin acetate or leuprolide acetate) does not

satisfy this inclusion criterion. Postmenopausal status is defined by one of the following:

• Age greater than or equal to 55 years and one year or more of amenorrhea

• Age greater than 55 years and one year or more of amenorrhea, with estradiol assay less than 20 pg per ml

and/or post-menopausal levels of FSH and LH per local institutional standards

• Prior hysterectomy, with estradiol assay less than 20 pg per ml and/or post-menopausal levels of

FSH and LH per local institutional standards

• Surgical menopause with bilateral oophorectomy.

4. Disease refractory to non-steroidal aromatase inhibitors (NSAI), defined as:

• Recurrence while on, or within 12 months (365 days) of completion of adjuvant

therapy with letrozole or anastrozole,

or

• Progression while on, or within one month (30 days) of completion of letrozole or

anastrozole treatment for ABC.

• Notes: Letrozole or anastrozole do not have to be the last treatment prior to study

baseline. Patients may have received one prior chemotherapy line for ABC, or

have received other endocrine treatments such as tamoxifen, or fulvestrant.

5. Radiological or objective evidence of recurrence or progression on or after the last

systemic therapy prior to enrolment.

• Notes: The last line of therapy may be any other treatment than exemestane and

mTOR inhibitors. Patients must have recovered to grade 1 or better from any adverse

events related to previous therapy (except alopecia) prior to enrolment.

6. Patients must have:

• Measurable disease defined as at least one lesion that can be accurately measured in

at least one dimension greater than or equal to 20 mm with conventional imaging techniques or greater than or equal to 10 mm

with spiral CT or MRI,

or

• Bone lesions: lytic or mixed (lytic + blastic) in the absence of measurable disease as

defined above.

Note: Lymph nodes must be greater than or equal to 15 mm in the short axis to be considered measurable

Patients with bone lesions and at least one measurable lesion are considered as having

measurable disease

If bone lesions have been previously irradiated, at least one lesion must have clearly

progressed since the radiotherapy by CT, MRI or X-ray for trial entry (in the absence

of measurable disease).

7. Adequate bone marrow and coagulation function as shown by:

• Absolute neutrophil count (ANC) greater than or equal to 1.5 x 10 raised to 9 per L

• Platelets greater than or equal to 100 Ã? 10 raised to 9 per L

• Hemoglobin (Hgb) greater than or equal to 9.0 g per dL

• INR less than or equal to 2.

8. Adequate liver function as shown by:

• Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 2.5

ULN (or less than or equ
Exclusion criteria: 1. Patients overexpressing HER2 by local laboratory testing (IHC 3 positive staining or in situ

hybridization positive), based on the most recent test. Patients with IHC 2 positive must have a

negative in situ hybridization test.

2. Patients with only non-measurable lesions other than bone metastasis (e.g. pleural effusion,

ascites).

3. Patients with more than one prior chemotherapy line for treating metastatic breast cancer.

A chemotherapy line is an anticancer regimen(s) that contains at least 1 cytotoxic

chemotherapy agent, given for a minimum of 21 days. A cytotoxic chemotherapy regimen

that lasted less than 21 days and was discontinued for a reason other than disease

progression is not accounted as a "prior line of chemotherapy".

4. Previous treatment with exemestane or mTOR inhibitors.

5. Known hypersensitivity to mTOR inhibitors, e.g. Sirolimus (rapamycin).

6. Any other malignancy within 5 years prior to enrolment, with the exception of adequately

treated in-situ carcinoma of the cervix uteri, basal or squamous skin cell carcinoma, or

non-melanoma skin cancer.

7. Radiotherapy within four weeks prior to enrolment, except radiotherapy to the bone for

analgesic purpose or for lytic lesions at risk of fracture. Patients must have recovered from

radiotherapy toxicities prior to enrolment.

8. Patient receiving hormone replacement therapy (HRT). Patient may be enrolled after

discontinuation of HRT.

9. History of brain or other CNS metastases.

10. Treatment with immunosuppressive agents or chronic corticosteroids, with the following

exceptions:

• Patients on stable low dose of systemic corticosteroids for at least two weeks before

enrolment

• Corticosteroids used in topical applications (e.g. cream), inhaled sprays, eye drops or

local (e.g. intra-articular) injections.

11. Bilateral diffuse lymphangitic carcinomatosis.

12. Patients with a known history of HIV seropositivity. Screening for HIV infection at

baseline is not required.

13. Active, bleeding diathesis. Patients treated with anti-vitamin K medication, LMWH, or

anti-platelet medication must have an INR <= 2.0.

14. Any severe and / or uncontrolled medical conditions such as:

a. Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction

less than or equal to 6 months prior to enrolment, serious uncontrolled cardiac arrhythmia

b. Uncontrolled diabetes as defined by fasting serum glucose more than 1.5 times ULN

c. Acute and chronic, active infectious disorders (except for Hep B and Hep C positive

patients) and non-malignant medical illnesses that are uncontrolled or whose control

may be jeopardized by the complications of this study therapy

d. Impairment of gastrointestinal function or who have gastrointestinal disease that may

significantly alter the absorption of study drugs (e.g., ulcerative disease, uncontrolled

nausea, vomiting, diarrhea, malabsorption syndrome)

e. Active skin, mucosa, ocular or gastro-intestinal disorders of Grade greater than 1

f. Significant symptomatic deterioration of lung function. If clinically indicated,

pulmonary function tests including measures of predicted lung volumes, DLco, O2

saturation at rest on room air

Age minimum:
Age maximum:
Gender:

Health Condition(s) or Problem(s) studied

Health Condition 1: null- Locally Advanced or Metastatic Breast Cancer

Intervention(s)

Intervention1: Everolimus (RAD001)and exemestane: All patients will receive everolimus 10 mg per day and exemestane 25 mg per day once daily by oral route.
Patients will continue to be treated per protocol until documentation of disease progression, unacceptable toxicity, death, discontinuation due to ant other reasons.
Control Intervention1: NIL: NIL

Primary Outcome(s)

To evaluate the safety and tolerability profile of everolimus in post-menopausal women with

ER positive, HER2 negative locally advanced or metastatic breast cancer after documented

recurrence or progression following a non-steroidal aromatase inhibitor therapy in Novartis

Oncology EGM countries.Timepoint: safety and tolerability will be based mainly on the frequency of adverse

events, including the laboratory values that qualify as adverse events.

Secondary Outcome(s)

To provide early access & To evaluate the efficacy of everolimus in postmenopausal

women with ER positive, HER2 negative

locally advanced or metastatic breast cancer after

documented recurrence or progression following a nonsteroidal

aromatase inhibitor therapy in EGM countries.

-To assess changes from baseline in Eastern

Cooperative Oncology Group (ECOG) performance

status over the study period.Timepoint: Efficacy endpoints will be analyzed on the Full Analysis Set (primary analysis) and on the Per

Protocol Set (supportive analysis).

Secondary ID(s)

CRAD001JIC06 version no.00 Release Date 26 Oct 2012

Source(s) of Monetary Support

Novartis Healthcare Private Limited, Sandoz house, Shivsagar Estate, Worli, Mumbai - 400012

Ethics review

Status: Approved
Approval date: 31/05/2013
Contact:

Noble Hospital Institutional Ethics Committee

Status: Approved
Approval date: 01/07/2013
Contact:

Human Research Ethics Committee

Status: Approved
Approval date: 05/09/2013
Contact:

Bombay Hospital Ethics Committee

Status: Approved
Approval date: 01/02/2014
Contact:

GCRI/GCS Ethics Committee

Status: Approved
Approval date: 24/02/2014
Contact:

Acharya Harihar Regional Cancer Centre Institutional Ethics Committee

Status: Approved
Approval date: 17/07/2014
Contact:

Manavata Clinical Research Institute Ethics Committee

Status: Not Approved
Approval date:
Contact:

Drug Trial Ethics Committee