Efficacy and Safety of Everolimus in Combination Therapy, in Patients With HER2-overexpressing Metastatic Breast Cancer

Novartis

Status and phase: Completed; Phase 1

Conditions: Metastatic Breast Cancer

Treatments: Drug: Everolimus; Drug: Paclitaxel; Drug: Trastuzumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT00426556

CRAD001J2101

2006-001596-37 (EudraCT Number)

Details and patient eligibility

About

Phase I: will look at different dose levels and regimens of everolimus combined with weekly trastuzumab and paclitaxel therapy in patients with HER-2 overexpressing metastatic breast cancer.

Phase II: will assess the efficacy and safety of the 10mg daily dose of everolimus combined with weekly trastuzumab and paclitaxel therapy in patients with HER-2 overexpressing metastatic breast cancer.

Enrollment: 88 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Female or male patients ≥ 18 years old with WHO performance status ≤ 1
• HER-2 over-expressing metastatic breast cancer cells confirmed by histology
• Progressive disease on prior trastuzumab alone/or in combination with other anticancer agents, or relapsed any time after completion of this therapy (phase l)
• Patient resistance to trastuzumab and taxanes (Phase ll)
• Measurable disease according to RECIST (Phase ll)
• Patients neurologically stable with adequate bone marrow, liver and renal function

Exclusion criteria

• Patients receiving endocrine therapy for breast cancer ≤ 2 weeks prior to study treatment start
• Patients currently receiving chemotherapy, immunotherapy or radiotherapy or who have received these ≤ 4 weeks prior to study treatment start or patients who have received lapatinib ≤ 2 weeks prior to study treatment start
• Patients who have previously received mTOR inhibitors

Other protocol-defined inclusion/exclusion criteria may apply

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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88 participants in 4 patient groups

Phase I - RAD001 5mg + PT, daily

Experimental group

Description:

Daily dosing schedule of EPT = Paclitaxel \& Trastuzumab verolimus 5mg plus Paclitaxel plus Trastuzumab.

Treatment:

Drug: Paclitaxel

Drug: Trastuzumab

Drug: Everolimus

Phase I - RAD001 10mg + PT, daily

Experimental group

Description:

Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab

Treatment:

Drug: Paclitaxel

Drug: Trastuzumab

Drug: Everolimus

Phase I - RAD001 30mg + PT, weekly

Experimental group

Description:

Weekly dosing schedule of Everolimus 30mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab.

Treatment:

Drug: Paclitaxel

Drug: Trastuzumab

Drug: Everolimus

Phase II - RAD001 10mg + PT, daily

Experimental group

Description:

Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab

Treatment:

Drug: Paclitaxel

Drug: Trastuzumab

Drug: Everolimus