RIBOCICLIB for Advanced hormone receptor-positive (HR+) breast cancer

Inclusion criteria

• {"criterion_text":"- Adult women (age ≥18 years) with advanced (metastatic or locally advanced) breast cancer not amenable to curative treatment by surgery or radiotherapy."}
• {"criterion_text":"- Histologic or cytologic confirmation of hormone-receptor positive (ER+ and/or PR+) breast cancer"}
• {"criterion_text":"- Postmenopausal women"}
• {"criterion_text":"- Dose Escalation: Any number of prior lines of endocrine therapy is allowed with up to one prior cytotoxic regimen in the advanced (metastatic or locally advanced) setting."}
• {"criterion_text":"- Dose Expansion Arm 1, 2 and 3: No prior systemic treatment in the advanced (metastatic or locally advanced) setting with the exception of treatment with letrozole or anastrozole for a maximum duration of one month."}
• {"criterion_text":"- Dose Expansion Arms 2 and 3 and Dose Escalation Arm 4: Patient has known PIK3CA status (mutated or non-mutated)"}
• {"criterion_text":"- Dose Escalation: Presence of measurable or non-measurable disease (as defined by RECIST 1.1 criteria)."}
• {"criterion_text":"- Dose Expansion: At least one measurable lesion, or lytic or mixed bone lesions in the absence of measurable disease (as defined by RECIST 1.1) for Arm 1 to Arm 3"}

Exclusion criteria

• {"criterion_text":"- HER2-overexpression in the patient’s tumor tissue by local laboratory testing (IHC 3+ or in situ hybridization positive)."}
• {"criterion_text":"- Patients with active CNS or other brain metastases. Patients with asymptomatic brain metastases that have been adequately treated and do not require corticosteroid therapy and /or enzyme inducing anti–epileptic medication for brain metastases are eligible."}
• {"criterion_text":"- Major surgery within 2 weeks"}
• {"criterion_text":"- Acute or chronic pancreatitis"}
• {"criterion_text":"- Bilateral diffuse lymphangitic carcinomatosis"}
• {"criterion_text":"- Another malignancy within 3 years"}
• {"criterion_text":"- Receiving hormone replacement therapy that cannot be discontinued"}
• {"criterion_text":"- Impaired cardiac function"}
• {"criterion_text":"- Patients with clinically manifest diabetes mellitus (treated and/or clinical signs or with fasting glucose ≥ 126 mg/dL / 7.0 mmol/L or hemoglobin A1c >6.5%), history of gestational diabetes mellitus or documented steroid-induced diabetes mellitus."}

Primary endpoints

• {"endpoint_text":"- Incidence of Dose Limiting Toxicities (DLTs) in Cycle 1 - Phase lb only [Time Frame: 28 days]","definition_or_measurement_approach":"Incidence of Dose Limiting Toxicities occurring during Cycle 1 (28-day period) assessed as DLT events during first cycle (Phase Ib)."}
• {"endpoint_text":"- Adverse Events (AEs), serious AEs (SAEs), changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs), dose interruptions, reductions and dose intensity.","definition_or_measurement_approach":"Safety monitoring including collection and assessment of AEs/SAEs, laboratory hematology and chemistry changes, vital signs, ECGs, and recording of dose interruptions/reductions and dose intensity."}
• {"endpoint_text":"- Plasma concentration-time profiles of LEE011, letrozole. PK parameters, including but not limited to AUC0-24h, Cmin, Cmax, Tmax, accumulation ratio (Racc).","definition_or_measurement_approach":"Pharmacokinetic profiling via plasma concentration-time measurements and calculation of PK parameters (AUC0-24h, Cmin, Cmax, Tmax, Racc, etc.)."}

Secondary endpoints

• {"endpoint_text":"- Plasma concentration-time profiles of LEE011, BYL719 and letrozole. PK parameters, including but not limited to AUC0-24h, Cmin, Cmax, Tmax, accumulation ratio (Racc).","definition_or_measurement_approach":"Pharmacokinetic plasma profiling and calculation of PK parameters for LEE011, BYL719 (alpelisib) and letrozole."}
• {"endpoint_text":"- Tumor response per RECIST v1.1 (by local investigator assessment): Overall Response Rate (ORR), Disease Control Rate (DCR), Clinical benefit Rate (CBR), Duration of Response (DOR) and Progression Free Survival (PFS) CBR is defined as CR, PR, or SD lasting 24 weeks or longer.","definition_or_measurement_approach":"Tumor assessments per RECIST v1.1 by local investigator to derive ORR, DCR, CBR (CR/PR/SD ≥24 weeks), DOR and PFS."}
• {"endpoint_text":"- Incidence of grade 3 or 4 hyperglycemia","definition_or_measurement_approach":"Incidence of laboratory-confirmed grade 3 or 4 hyperglycemia assessed per toxicity grading criteria (e.g., CTCAE)."}
• {"endpoint_text":"- Incidence of grade 3 or 4 AST/ALT elevations","definition_or_measurement_approach":"Incidence of grade 3 or 4 elevations in AST/ALT measured by laboratory tests and graded per toxicity criteria."}

France

Earliest CTIS Part Ii Submission Date

18-03-2024

Latest Decision Or Authorization Date

03-05-2024

Processing Time Days

46

Number Of Sites

1

Number Of Participants

37

Spain

Earliest CTIS Part Ii Submission Date

18-03-2024

Latest Decision Or Authorization Date

02-12-2025

Processing Time Days

624

Number Of Sites

3

Number Of Participants

46

Primary sponsor

Full Name

Novartis Pharma AG

Organisation Type

Pharmaceutical company

Country Of Registered Address

Switzerland

Contract research organisations

Name

Rps Research Iberica S.L.

Responsibilities

code 1

Name

IQVIA RDS Spain S.L.

Responsibilities

code 1

Name

Syneos Health Clinical Spain S.L.

Responsibilities

code 1

Name

Veeda Clinical Research Limited

Responsibilities

code 4

Third parties

• {"country":"China","full_name":"Wuxi Apptec Co. Ltd.","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"Kit supplier and sample management","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Rps Research Iberica S.L.","duties_or_roles":"code 1","organisation_type":"Pharmaceutical company"}
• {"country":"India","full_name":"Veeda Clinical Research Limited","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"IQVIA RDS Spain S.L.","duties_or_roles":"code 1","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Syneos Health Clinical Spain S.L.","duties_or_roles":"code 1","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Creapharm Clinical Supplies","duties_or_roles":"Study Drugs distribution, storage, relabeling, return and destruction","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"Cardiac safety (ECG central read)","organisation_type":"Pharmaceutical company"}