A Phase II Study of Everolimus in Combination With Exemestane Versus Everolimus Alone Versus Capecitabine in Advance Breast Cancer

Phase 2

Completed

• Conditions: Health Condition 1: null- locally advanced, recurrent, or metastatic breast cancer

• Registration Number: CTRI/2014/03/004444
• Lead Sponsor: ovartis Healthcare Pvt Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 27 May 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 0

Inclusion Criteria

1. Women with locally advanced, recurrent, or metastatic breast cancer. Locally advanced

breast cancer is 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. Postmenopausal status is defined either by:

• Age greater than or equal to 18 with prior bilateral oophorectomy

• Age greater than or equal to 60 years

• Age less than 60 years with amenorrhea for at least 12 months and both follicle-stimulating

hormone (FSH) and estradiol levels are in postmenopausal range (according to the

local laboratory)

Note: Ovarian radiation or treatment with a luteinizing hormone-releasing hormone

(LHRH) agonist (goserelin acetate or leuprolide acetate) does not satisfy this

inclusion criterion.

4. Recurrence or progression on prior NSAIs is defined as:

• Recurrence while on, or within one year (365 days) of end of adjuvant treatment with

an aromatase inhibitor

OR

• Progression while on, or within one month (30 days) of the end of, prior treatment

with an aromatase inhibitor for ABC

Notes:

• Letrozole or anastrozole do not have to be the last treatment prior to randomization

• Patients must have recovered to grade 1 or better from any adverse events (except

alopecia) related to previous therapy prior to randomization

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

systemic therapy prior to randomization

6. Patients must have either:

• Measurable disease defined as at least one lesion = 10 mm by CT or MRI that can be

accurately measured in at least one dimension (CT scan slice thickness less than or equal to 5 mm)

OR

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

defined above

Notes:

• Lymph nodes have to be gretaer than or equal to 15 mm in short axis to be considered measurable

• 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 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 10raised to 9 per L

• Platelets greater than or equal to 100 × 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 equal to 5 if hepatic metastases are present).

• Total serum bilirubin less than or equal to 1.5 × ULN (less than or equal to 3 × ULN for patients known to have Gilbert

Syndrome)

9. Adequate renal function as shown by serum creatinine less than or equal to 1.5 × ULN

10. Fasting serum cholesterol less than or equal to 300 mg per dl and fasting triglycerides less than or equal to 2.5 x ULN

11. ECOG Performance Status less than or equal to 2

12. Left ventricular ejection fraction assessment (echocardiogram or MUGA scan) performed

within 4 weeks prior to randomization, showing a LVEF value gre

Exclusion Criteria

Patients eligible for this study must not meet any of the following criteria:

1. HER2-overexpressing patients by local laboratory testing (IHC 3+ staining or in situ

hybridization positive), based on the most recent test. Note: Patients with IHC 2+ must

have a negative in situ hybridization test

2. Patients who received more than one chemotherapy line for ABC

Note: A chemotherapy line in advanced disease is an anticancer regimen that contains at

least one chemotherapy agent and is given for 21 days or longer. If a cytotoxic

chemotherapy regimen was discontinued for a reason other than disease progression and

lasted less than 21 days, then this regimen does not count as a prior line of

chemotherapy. Chemotherapy regimens composed of more than one drug are considered

as one line of therapy.

3. Patients with only non-measurable lesions other than lytic or mixed (lytic and blastic)

bone metastasis (e.g. pleural effusion, ascites etc.)

4. Previous treatment with exemestane, mTOR inhibitors, PI3K inhibitors or AKT inhibitors.

5. Patients who received a fluoropyrimidine-containing regimen as a prior chemotherapy

treatment within 24 weeks prior to randomization

6. Known hypersensitivity to mTOR inhibitors, e.g. sirolimus (rapamycin) or known

hypersensitivity to capecitabine or to any of its components or to 5-fluorouracil

7. Patients with known rare hereditary problems of galactose intolerance, the lapp lactase

deficiency, glucose-galactose malabsorption or dihydropyrimidine dehydrogenase (DPD)

deficiency.

8. Another malignancy within 5 years prior to randomization, with the exception of

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

non-melanomatous cancer of skin or history of stage IA melanoma that has been cured.

9. Radiotherapy within four weeks prior to randomization except in case of localized

palliative radiotherapy (for analgesic purpose) or for lytic lesions at risk of fracture which

was completed at least two weeks prior to randomization. Patients must have recovered

from radiotherapy toxicities.

Note: Lesions in previously irradiated areas should not be considered measurable, unless

they have clearly progressed since the radiotherapy. If lesions in previously irradiated

areas have not progressed since the radiotherapy, they should be considered nonmeasurable

and followed as non-target lesions

10. Currently receiving any hormone replacement therapy, unless discontinued prior to

randomization.

11. Current or history of CNS metastases. Patients with symptoms suggestive of CNS

metastases should have a CT/MRI to rule out CNS metastasis prior to randomization to be

eligible.

12. Patients receiving concomitant immunosuppressive agents or chronic corticosteroids use

at the time of study entry except topical applications, inhaled sprays, eye drops or local

injections.

13. Bilateral diffuse lymphangitic carcinomatosis

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

baseline is not required.

15. Active, bleeding diathesis, or on oral anti-vitamin K medication (except low dose warfarin,

LMWH and acetylsalicylic acid or equivalent, as long as the INR is =2)

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To estimate the hazard ratio of PFS for everolimus <br/ ><br>plus exemestane versus everolimus alone in <br/ ><br>postmenopausal women with ER positive, HER2 <br/ ><br>negative, advanced breast cancer after recurrence or <br/ ><br>progression on letrozole or anastrozole.Timepoint: Progression free survival (PFS) based on the local radiologist/investigators tumor assessment (RECIST 1.1)