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

Launched by MEDICAL UNIVERSITY OF GDANSK · Oct 4, 2021

Keywords

ClinConnect Summary

The "CARE" clinical trial is studying different treatment options for people with triple-negative breast cancer (TNBC), a type of breast cancer that does not respond to some common hormonal therapies. This trial will look at how well various combinations of medications, including palbociclib and paclitaxel, work in treating TNBC before surgery. Patients who might be eligible for this study are adults over 18 years old who have a confirmed diagnosis of TNBC and have not received any previous treatment for this cancer. They should also have measurable tumors that can be biopsied.

If you join this study, you will be randomly assigned to one of five treatment groups. The trial will involve some tests and procedures, including biopsies to confirm your diagnosis and monitor your health. You will need to agree to follow specific guidelines, including using birth control if you are of child-bearing potential. It's important to know that the trial is not yet recruiting participants, but it aims to gather valuable information about potential treatments for TNBC.

Gender

ALL

Eligibility criteria

• 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.