Everolimus in Treating Patients WIth Recurrent or Metastatic Breast Cancer

NCIC Clinical Trials Group

Status and phase

Completed

Phase 2

Conditions

Breast Cancer

Treatments

Drug: everolimus

Study type

Interventional

Funder types

NETWORK

Identifiers

NCT00255788

CDR0000450849 (Other Identifier)

I163

NOVARTIS-CAN-NCIC-IND163 (Other Identifier)

CAN-NCIC-IND163 (Other Identifier)

Details and patient eligibility

About

RATIONALE: Everolimus may stop the growth of tumor cells by blocking blood flow to the tumor.

PURPOSE: This randomized phase II trial is studying two different schedules of everolimus to see how well they work in treating patients with recurrent or metastatic breast cancer.

Full description

OBJECTIVES:

Primary

Determine the efficacy of 2 different treatment schedules of everolimus, in terms of clinical/radiological response and early progression, in patients with recurrent or metastatic breast cancer.

Secondary

Determine the time to progression and response duration in patients treated with these regimens.
Determine the toxic effects of these regimens in these patients.
Correlate molecular markers of mTOR activity in tumor tissue with objective tumor response in patients treated with these regimens.

OUTLINE: This is a randomized, open label, multicenter study. Patients are stratified according to presence of visceral metastases (yes vs no) and prior chemotherapy regimens for recurrent disease (0 vs 1). Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive oral everolimus once daily on days 1-28.
Arm II: Patients receive oral everolimus on days 1, 8, 15, and 22. In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 4 weeks and then periodically until disease progression.

PROJECTED ACCRUAL: A total of 60 patients (30 per treatment arm) will be accrued for this study.

Enrollment

49 patients

Sex

All

Ages

16 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Histologically confirmed breast cancer
- Metastatic or recurrent disease
- Considered incurable
Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan
Two primary breast cancers allowed
Paraffin-embedded primary or metastatic tumor sample available
No known brain metastases
Hormone receptor status:
- Not specified

PATIENT CHARACTERISTICS:

Sex

Male or female

Menopausal status

Not specified

Performance status

ECOG 0-2

Life expectancy

Not specified

Hematopoietic

Absolute granulocyte count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3

Hepatic

Bilirubin ≤ 1.5 times upper limit of normal (ULN)
AST and ALT ≤ 2.5 times ULN

Renal

Creatinine ≤ 1.5 times ULN

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No active uncontrolled infection
No upper gastrointestinal condition or other condition that would preclude ability to take oral medication
No other serious medical condition that would preclude study participation
No psychiatric illness or neurologic disorder that would preclude study compliance
No other malignancy within the past 5 years except curatively treated nonmelanoma skin cancer or carcinoma in situ of the cervix or bladder

PRIOR CONCURRENT THERAPY:

Chemotherapy

At least 4 weeks since prior chemotherapy
Prior adjuvant chemotherapy allowed
No more than 1 prior chemotherapy regimen for metastatic or recurrent disease

Endocrine therapy

At least 5 days since prior hormonal therapy

Radiotherapy

At least 4 weeks since prior radiotherapy except for low-dose, limited-fraction, palliative, nonmyelosuppressive radiotherapy, defined as radiotherapy to < 20% of functioning bone marrow
If prior radiotherapy was to sole site of disease, must have subsequent documented disease progression at that site

Surgery

At least 3 weeks since prior major surgery

Other

Concurrent prophylactic bisphosphonates allowed, if started prior to study entry
No concurrent potent inhibitors of cytochrome 3A4, such as erythromycin, diltiazem, or ketoconazole and similar antifungals
No other concurrent anticancer therapy
No other concurrent investigational agents
No concurrent grapefruit juice