CAREGIVER: Cyclin dEpendent Kinase in tRiple nEGatIVe brEast canceR - a "Window of Opportunity" Study
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: CDK4/6 inhibitor alone: Palbociclib (IMP) Palbociclib alone (125 mg orally (PO) per day, days 1-14) |
Drug: Palbociclib
CDK4/6 inhibitor
Other Names:
|
| Active Comparator: Chemotherapy alone: Paclitaxel Paclitaxel alone (80 mg/m^2 intravenously (IV), day 1, 8, 15 and 22) |
Drug: Paclitaxel
Chemotherapy
|
| Experimental: CDK4/6 inhibitor + chemotherapy: Paclitaxel + Palbociclib Paclitaxel (80 mg/m^2 IV, day 1, 8, 15 and 22) + Palbociclib (125 mg PO per day, days 1-21) |
Drug: Palbociclib
CDK4/6 inhibitor
Other Names:
Drug: Paclitaxel
Chemotherapy
|
| Active Comparator: Chemotherapy alone: Carboplatin Carboplatin alone (area under the curve (AUC) 2 IV, day 1, 8, 15 and 22) |
Drug: Carboplatin
Chemotherapy
|
| Experimental: CDK4/6 inhibitor + chemotherapy: Carboplatin + Palbociclib Carboplatin (AUC 2 IV, day 1, 8, 15 and 22) + Palbociclib (125 mg PO per day, days 1-21) |
Drug: Palbociclib
CDK4/6 inhibitor
Other Names:
Drug: Carboplatin
Chemotherapy
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
- 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.
- Tumor diameter change [Day 27 (± 3 days)]
Maximum tumor diameter change in largest continuous tumor mass based on MR imaging.
- 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).
Eligibility Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Dolnośląskie Centrum Onkologii we Wrocławiu, Oddział Onkologii Klinicznej/Chemioterapii, Poradnia Chemioterapii; Leczenie Nowotworów Piersi | Wrocław | Dolnośląskie | Poland | 53-413 |
| 2 | Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie | Warsaw | Mazowieckie | Poland | 22 546 20 00 |
| 3 | SP ZOZ Opolskie Centrum Onkologii im. Prof. Tadeusza Koszarowskiego | Opole | Opolskie | Poland | 45-061 |
| 4 | Uniwersyteckie Centrum Kliniczne, Klinika Onkologii i Radioterapii | Gdańsk | Pomorskie | Poland | 80-952 |
| 5 | Wielkopolskie Centrum Onkologii im. Marii Skłodowskiej-Curie, Oddział Onkologii Klinicznej i Immunoonkologii z Pododdziałem Dziennym | Poznań | Wielkopolskie | Poland | 61 885 05 57 |
| 6 | Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie, Państwowy Instytut Badawczy, Oddział w Gliwicach | Gliwice | Śląskie | Poland | 44-102 |
Sponsors and Collaborators
- Medical University of Gdansk
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NBK 171/1/2021
- 2021-001556-33