Triple Negative Breast Neoplasms
Conditions
Brief 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.
Interventions
DRUGPalbociclib
CDK4/6 inhibitor
DRUGPaclitaxel
Chemotherapy
DRUGCarboplatin
Chemotherapy
Sponsors
Medical University of Gdansk
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This 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)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Early metabolic response | Day 27 (± 3 days) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) | Day 27 (± 3 days) | 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. |
| Metabolic tumor volume (MTV) difference | Day 27 (± 3 days) | Difference in metabolic tumor volume (MTV) regression between chemotherapy + palbociclib vs chemotherapy alone arms. |
| SUVmax change | Day 27 (± 3 days) | Difference in proportion of patients with SUVmax change above the predefined cut-off of 30% between chemotherapy + palbociclib vs chemotherapy alone arms. |
| Change in tumor characteristic | Day 27 (± 3 days) | Change in tumor characteristic in Day 27 biopsy (presence of viable cancer cells). |
| Treatment toxicity | Day 27 (± 3 days) | 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). |
| Tumor diameter change | Day 27 (± 3 days) | Maximum tumor diameter change in largest continuous tumor mass based on MR imaging. |
Countries
Poland
Contacts
Primary ContactElżbieta Senkus-Konefka, MD, PhD
Backup ContactMonika Puchowska, MSc
Outcome results
None listed