Cyclin dEpendent Kinase in tRiple nEGatIVe brEast canceR - a "Window of Opportunity" Study

Обзор

CAREGIVER is a prospective, randomized, multicenter, open, five-arm study with unequal allocation ratios of 1:1:2:1:2 (palbociclib : paclitaxel : palbociclib + paclitaxel : carboplatin : carboplatin + paclitaxel). Study will be performed in untreated patients with triple-negative breast cancer (TNBC). Potential candidates without previously established diagnosis of TNBC will be included in a Pre-screening Phase, when a biopsy of breast tumor will be taken to confirm the diagnosis of cancer, select patients with TNBC and collect tissue for translational research.

Вмешательства

• Препарат Palbociclib
  CDK4/6 inhibitor
• Препарат Paclitaxel
  Chemotherapy
• Препарат Carboplatin
  Chemotherapy

Первичные конечные точки

• Early metabolic response [Срок оценки: Day 27 (± 3 days)]

Вторичные конечные точки (6)

• SUVmax change [Срок оценки: Day 27 (± 3 days)]
• Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) [Срок оценки: Day 27 (± 3 days)]
• Metabolic tumor volume (MTV) difference [Срок оценки: Day 27 (± 3 days)]
• Tumor diameter change [Срок оценки: Day 27 (± 3 days)]
• Change in tumor characteristic [Срок оценки: Day 27 (± 3 days)]
• Treatment toxicity [Срок оценки: Day 27 (± 3 days)]

Критерии участия

Критерии включения

• females or males >18 years old at the time of informed consent signature;
• diagnosis of potentially resectable or de novo metastatic (stage II-IV) invasive carcinoma of the breast;
• eligible for standard neoadjuvant or palliative paclitaxel and/or carboplatin-based chemotherapy as determined by Investigator;
• triple negative tumor defined as:

• hormone receptor-negative (<1% ER/PgR expression);
• HER2-negative (Immunohistochemistry (IHC) score ≤1 or IHC score =2 and negative for the amplification by in situ hybridization);
• multicentric/multifocal disease is allowed, provided that all lesions have been biopsied and their phenotype has been confirmed pathologically as TNBC;
• no previous anticancer therapy for this malignancy;
• clinically or radiographically measurable disease (discrete lesion only, enhancement is not included) within the breast, that can be biopsied, defined as longest diameter >2 cm;
• multicentric or multifocal disease is allowed if at least 1 lesion is >2 cm;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
• adequate bone marrow and organ function as defined by the following local laboratory values:
• hemoglobin ≥9 g/dL;
• absolute neutrophil count (ANC) ≥1500/μL;
• platelets ≥100,000/μL;
• total bilirubin ≤ institutional upper limit of normal (ULN), unless diagnosis of Gilbert syndrome;
• aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5x ULN;
• creatinine ≤ ULN OR creatinine clearance ≥50 mL/min per Cockcroft-Gault equation for patients with creatinine levels greater than ULN.
• blood glucose level <120 mg/dL after at least 6 hours of fasting;
• standard 12-lead electrocardiogram (ECG) without clinically significant abnormalities;
• ability to undergo contrast-enhanced MRI;
• ability to swallow and retain oral medication;
• all study participants of child-bearing potential must agree to use adequate contraceptive methods prior to study entry, during the study and for the following 3 weeks (females) or 14 weeks (males);
• prior chemotherapy, other targeted anticancer therapies, or prior radiation therapy (outside of treated breast) for other malignancy treated with radical intent is allowed, provided the treatment was completed ≥1 year before informed consent signature;
• prior bisphosphonate therapy is allowed;
• willing and able to undergo all the procedures required by the study protocol;
• provision of written informed consent form prior to receiving any study related procedure.

Критерии исключения

• inflammatory breast cancer;
• prior systemic treatment for this malignancy;
• prior treatment with CDK4/6 inhibitor;
• known hypersensitivity to study medications or any of their excipients;
• major surgery or radiotherapy (apart from limited field radiotherapy for symptom control) within 14 days prior to randomization;
• concurrent invasive malignancy;
• known HIV, active HBV or HCV infection;
• active autoimmune disease requiring ongoing immunosuppressive therapy;
• history of allotransplantation;
• concurrent treatment with systemic immunosuppressive agents, including steroids, within 3 weeks of enrolment;
• presence of implants or devices not compatible with MRI;
• pregnant or nursing female participants;
• receiving strong inhibitors or inducers of CYP3A4/5 or medications with narrow therapeutic window that are predominantly metabolized through CYP3A4/5;
• impairment of GI function that may significantly alter the absorption of the oral trial treatments;
• unwilling or unable to follow protocol requirements, including obligatory biopsies;
• any condition which in the Investigator's opinion deems the participant an unsuitable candidate to receive study drugs;
• any other concurrent severe and/or uncontrolled medical condition that would, in the Investigator's judgment, contraindicate patient participation in the clinical trial or compromise compliance with the protocol.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Польша · 6 центров

• Wielkopolskie Centrum Onkologii im. Marii Skłodowskiej-Curie, Oddział Onkologii Klinicznej — Poznan
• Dolnośląskie Centrum Onkologii we Wrocławiu, Oddział Onkologii Klinicznej/Chemioterapii, P — Wroclaw
• Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie — Warsaw
• SP ZOZ Opolskie Centrum Onkologii im. Prof. Tadeusza Koszarowskiego — Opole
• Uniwersyteckie Centrum Kliniczne, Klinika Onkologii i Radioterapii — Gdansk
• Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie, Państwowy Instytut Badawczy, Odd — Gliwice

Идентификаторы

NCT: NCT05067530 · NBK 171/1/2021 · 2021-001556-33

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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