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

Medical University of Gdansk

Status and phase: Not yet enrolling; Phase 2

Conditions: Triple Negative Breast Neoplasms

Treatments: Drug: Paclitaxel; Drug: Palbociclib; Drug: Carboplatin

Study type: Interventional

Funder types: Other

Identifiers

NCT05067530

2021-001556-33 (EudraCT Number)

NBK 171/1/2021

Details and patient eligibility

About

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.

Enrollment: 126 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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126 participants in 5 patient groups

CDK4/6 inhibitor alone: Palbociclib (IMP)

Experimental group

Description:

Palbociclib alone (125 mg orally (PO) per day, days 1-14)

Treatment:

Drug: Palbociclib

Chemotherapy alone: Paclitaxel

Active Comparator group

Description:

Paclitaxel alone (80 mg/m\^2 intravenously (IV), day 1, 8, 15 and 22)

Treatment:

Drug: Paclitaxel

CDK4/6 inhibitor + chemotherapy: Paclitaxel + Palbociclib

Experimental group

Description:

Paclitaxel (80 mg/m\^2 IV, day 1, 8, 15 and 22) + Palbociclib (125 mg PO per day, days 1-21)

Treatment:

Drug: Palbociclib

Drug: Paclitaxel

Chemotherapy alone: Carboplatin

Active Comparator group

Description:

Carboplatin alone (area under the curve (AUC) 2 IV, day 1, 8, 15 and 22)

Treatment:

Drug: Carboplatin

CDK4/6 inhibitor + chemotherapy: Carboplatin + Palbociclib

Experimental group

Description:

Carboplatin (AUC 2 IV, day 1, 8, 15 and 22) + Palbociclib (125 mg PO per day, days 1-21)

Treatment:

Drug: Palbociclib

Drug: Carboplatin