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

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ClinicalTrials.gov Identifier: NCT05067530
Recruitment Status : Not yet recruiting
First Posted : October 5, 2021
Last Update Posted : October 5, 2021
Sponsor:
Information provided by (Responsible Party):
Medical University of Gdansk

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
Triple Negative Breast Neoplasms Drug: Palbociclib Drug: Paclitaxel Drug: Carboplatin Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 126 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
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)
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Cyclin dEpendent Kinase in tRiple nEGatIVe brEast canceR - a "Window of Opportunity" Study
Estimated Study Start Date : January 1, 2022
Estimated Primary Completion Date : January 1, 2025
Estimated Study Completion Date : December 6, 2026

Resource links provided by the National Library of Medicine

Drug Information available for: Palbociclib

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 Name: Ibrance

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 Name: Ibrance

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 Name: Ibrance

Drug: Carboplatin
Chemotherapy




Primary Outcome Measures :
  1. Early metabolic response [ Time Frame: 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 :
  1. SUVmax change [ Time Frame: 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.

  2. Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) [ Time Frame: 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.

  3. Metabolic tumor volume (MTV) difference [ Time Frame: Day 27 (± 3 days) ]
    Difference in metabolic tumor volume (MTV) regression between chemotherapy + palbociclib vs chemotherapy alone arms.

  4. Tumor diameter change [ Time Frame: Day 27 (± 3 days) ]
    Maximum tumor diameter change in largest continuous tumor mass based on MR imaging.

  5. Change in tumor characteristic [ Time Frame: Day 27 (± 3 days) ]
    Change in tumor characteristic in Day 27 biopsy (presence of viable cancer cells).

  6. Treatment toxicity [ Time Frame: 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).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05067530


Contacts
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Contact: Elżbieta Senkus-Konefka, MD, PhD 58 584 4482 ext 0048 elzbieta.senkus-konefka@gumed.edu.pl
Contact: Monika Puchowska, MSc 58 349 1885 ext 0048 monika.puchowska@gumed.edu.pl

Locations
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Poland
Dolnośląskie Centrum Onkologii we Wrocławiu, Oddział Onkologii Klinicznej/Chemioterapii, Poradnia Chemioterapii; Leczenie Nowotworów Piersi
Wrocław, Dolnośląskie, Poland, 53-413
Contact: Aleksandra Łacko, MD, PhD    71 368 94 83 ext 0048    aleksandra.lacko@umed.wroc.pl   
Principal Investigator: Aleksandra Łacko, MD, PhD         
Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie
Warsaw, Mazowieckie, Poland, 22 546 20 00
Contact: Agnieszka Jagiełło-Gruszfeld, MD, PhD    22 546 20 00 ext 0048    agnieszka.jagiello-gruszfeld@gmail.com   
Principal Investigator: Agnieszka Jagiełło-Gruszfeld, MD, PhD         
SP ZOZ Opolskie Centrum Onkologii im. Prof. Tadeusza Koszarowskiego
Opole, Opolskie, Poland, 45-061
Contact: Barbara Stefania Radecka, MD, PhD    77 441 60 01 ext 0048    brad@onkologia.opole.pl   
Principal Investigator: Barbara Stefania Radecka, MD, PhD         
Uniwersyteckie Centrum Kliniczne, Klinika Onkologii i Radioterapii
Gdańsk, Pomorskie, Poland, 80-952
Principal Investigator: Elżbieta Senkus-Konefka, MD, PhD         
Wielkopolskie Centrum Onkologii im. Marii Skłodowskiej-Curie, Oddział Onkologii Klinicznej i Immunoonkologii z Pododdziałem Dziennym
Poznań, Wielkopolskie, Poland, 61 885 05 57
Contact: Maria Małgorzata Litwiniuk, MD, PhD    61 885 05 57 ext 0048    maria.litwiniuk@wco.pl   
Principal Investigator: Maria Małgorzata Litwiniuk, MD, PhD         
Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie, Państwowy Instytut Badawczy, Oddział w Gliwicach
Gliwice, Śląskie, Poland, 44-102
Contact: Michał Jarząb, MD, PhD    32 278 88 86 ext 0048    michal.jarzab@io.gliwice.pl   
Principal Investigator: Michał Jarząb, MD, PhD         
Sponsors and Collaborators
Medical University of Gdansk
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Responsible Party: Medical University of Gdansk
ClinicalTrials.gov Identifier: NCT05067530    
Other Study ID Numbers: NBK 171/1/2021
2021-001556-33 ( EudraCT Number )
First Posted: October 5, 2021    Key Record Dates
Last Update Posted: October 5, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Triple Negative Breast Neoplasms
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Carboplatin
Palbociclib
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors
Enzyme Inhibitors