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

Triple Negative Breast Neoplasms Clinical Trial

— CAREGIVER  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05067530
• Other study ID #: NBK 171/1/2021
• Secondary ID: 2021-001556-33
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: January 1, 2022
• Est. completion date: December 6, 2026

Study information

• Verified date: October 2021
• Source: Medical University of Gdansk
• Contact: Elzbieta Senkus-Konefka, MD, PhD
• Phone: 58 584 4482
• Email: elzbieta.senkus-konefka[@]gumed.edu.pl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 126
• Est. completion date: December 6, 2026
• Est. primary completion date: January 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Neoplasms
• Triple Negative Breast Neoplasms

Intervention

Drug:
• Palbociclib
CDK4/6 inhibitor
• Paclitaxel
Chemotherapy
• Carboplatin
Chemotherapy

Locations

Country	Name	City	State
Poland	Uniwersyteckie Centrum Kliniczne, Klinika Onkologii i Radioterapii	Gdansk	Pomorskie
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie, Panstwowy Instytut Badawczy, Oddzial w Gliwicach	Gliwice	Slaskie
Poland	SP ZOZ Opolskie Centrum Onkologii im. Prof. Tadeusza Koszarowskiego	Opole	Opolskie
Poland	Wielkopolskie Centrum Onkologii im. Marii Sklodowskiej-Curie, Oddzial Onkologii Klinicznej i Immunoonkologii z Pododdzialem Dziennym	Poznan	Wielkopolskie
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie	Warsaw	Mazowieckie
Poland	Dolnoslaskie Centrum Onkologii we Wroclawiu, Oddzial Onkologii Klinicznej/Chemioterapii, Poradnia Chemioterapii; Leczenie Nowotworów Piersi	Wroclaw	Dolnoslaskie

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Gdansk

Country where clinical trial is conducted

Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Early metabolic response	Difference in early (i.e., after three weeks of therapy, 1 cycle) metabolic response to treatment in chemotherapy-containing arms (chemotherapy ± palbociclib), as assessed by Blinded Central Review comparison of decrease in SUVmax between baseline and Day 27 (± 3 days) 18-fluoro-2-deoxy-d-glucose (18FDG) positron emission tomography - computed tomography (PET-CT). Primary analysis will include comparison between chemotherapy + palbociclib vs chemotherapy alone arms.	Day 27 (± 3 days)
Secondary	SUVmax change	Difference in proportion of patients with SUVmax change above the predefined cut-off of 30% between chemotherapy + palbociclib vs chemotherapy alone arms.	Day 27 (± 3 days)
Secondary	Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST)	Difference in Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST)-based peak standardized uptake value corrected for lean body mass in a spherical 1 cm3 volume of interest (SULpeak) decrease in PET-CT between chemotherapy + palbociclib vs chemotherapy alone arms.	Day 27 (± 3 days)
Secondary	Metabolic tumor volume (MTV) difference	Difference in metabolic tumor volume (MTV) regression between chemotherapy + palbociclib vs chemotherapy alone arms.	Day 27 (± 3 days)
Secondary	Tumor diameter change	Maximum tumor diameter change in largest continuous tumor mass based on MR imaging.	Day 27 (± 3 days)
Secondary	Change in tumor characteristic	Change in tumor characteristic in Day 27 biopsy (presence of viable cancer cells).	Day 27 (± 3 days)
Secondary	Treatment toxicity	Treatment toxicity (with special attention to myeloid toxicity to explore potential myeloprotective activity): number and severity of adverse events (AEs); toxicity will be described according to ICD-10 codes and graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0).	Day 27 (± 3 days)