A Phase Ib Dose Escalation Study of the Combination of LEE011 With Letrozole and Dose Expansion of LEE011 With Hormonal Therapy for the Treatment of Pre-(With Goserelin) and Postmenopausal Women With Hormone Receptor Positive, HER2-negative, Advanced Breast Cancer

Novartis

Status and phase: Completed; Phase 1

Conditions: Hormone Receptor Positive, HER2-negative, Advanced Breast Cancer

Treatments: Drug: Fulvestrant; Drug: goserelin; Drug: Letrozole; Drug: Tamoxifen; Drug: LEE011

Study type: Interventional

Funder types: Industry

Identifiers

NCT02333370

CLEE011A2115C

Details and patient eligibility

About

The purpose of the Phase Ib is to:

1. determine the recommended dose of LEE011 in combination with a standard dose of letrozole as well as to provide additional safety and anti-tumor activity data in Asian non-Japanese patients
2. determine the recommended dose of LEE011 in combination with a standard dose of letrozole as well as to provide additional safety and activity data in Japanese patients
3. evaluate the safety and anti-tumor activity of LEE011 at the RP2D established in the dose escalation part in combination with a standard dose of letrozole, fulvestrant or tamoxifen plus goserelin in Japanese patients.

Enrollment: 88 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Women with advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative therapy (surgery and/or radiotherapy).
• Patient has a histologically and/or cytologically confirmed diagnosis of estrogen receptor positive and/or progesterone receptor positive breast cancer
• Patient has HER2-negative breast cancer
• Patient has adequate bone marrow and organ function

Exclusion criteria

• Patient who received any CDK4/6 inhibitor.
• Patient has a known hypersensitivity to any of the excipients of LEE011 or letrozole
• Patients with inflammatory breast cancer.
• Patient who received any prior systemic anti-cancer therapy (including hormonal therapy and chemotherapy) for advanced breast cancer
• Patient is currently using other anti-cancer therapy
• Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects.
• Patient who has received radiotherapy ≤ 4 weeks
• Patient has a concurrent malignancy or malignancy within 3 years
• Patient has metastases to the central nervous system (CNS).
• Patient has a known history of HIV infection

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 3 patient groups

LEE011 +Letrozole

Experimental group

Description:

LEE011 - 3 weeks on 1 week off Letrozole 2.5mg - Once daily

Treatment:

Drug: LEE011

Drug: Letrozole

LEE011 + Tamoxifen

Experimental group

Description:

LEE011 - 3 weeks on 1 week off Tamoxifen 20mg - Once daily

Treatment:

Drug: Tamoxifen

Drug: goserelin

LEE011 + Fulvestrant

Experimental group

Description:

LEE011 - 3 weeks on 1 week off Fulvestrant 500 mg - Dosed every 28 days (Day 1 for each cycle) with 1 additional dose on Day 15 of Cycle 1

Treatment:

Drug: Fulvestrant