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

NCT05067530 | Not Yet Recruiting Phase 2 DMC

• 2 other identifiers: NBK 171/1/20212021-001556-33
• Study Type: interventional
• Target: 126
• Locations: 1 country
• Sites: 6

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.

Conditions

Triple Negative Breast Neoplasms

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• SUVmax change

  Day 27 (± 3 days)

• Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST)

  Day 27 (± 3 days)

• Metabolic tumor volume (MTV) difference

  Day 27 (± 3 days)

• Tumor diameter change

  Day 27 (± 3 days)

• Change in tumor characteristic

  Day 27 (± 3 days)

Study Arms (5)

CDK4/6 inhibitor alone: Palbociclib (IMP)

EXPERIMENTAL

Palbociclib alone (125 mg orally (PO) per day, days 1-14)

Drug: Palbociclib

Chemotherapy alone: Paclitaxel

ACTIVE COMPARATOR

Paclitaxel alone (80 mg/m\^2 intravenously (IV), day 1, 8, 15 and 22)

Drug: Paclitaxel

CDK4/6 inhibitor + chemotherapy: Paclitaxel + Palbociclib

EXPERIMENTAL

Paclitaxel (80 mg/m\^2 IV, day 1, 8, 15 and 22) + Palbociclib (125 mg PO per day, days 1-21)

Drug: Palbociclib; Drug: Paclitaxel

Chemotherapy alone: Carboplatin

ACTIVE COMPARATOR

Carboplatin alone (area under the curve (AUC) 2 IV, day 1, 8, 15 and 22)

Drug: Carboplatin

CDK4/6 inhibitor + chemotherapy: Carboplatin + Palbociclib

EXPERIMENTAL

Carboplatin (AUC 2 IV, day 1, 8, 15 and 22) + Palbociclib (125 mg PO per day, days 1-21)

Drug: Palbociclib; Drug: Carboplatin

Interventions

Palbociclib DRUG

CDK4/6 inhibitor

Also known as: Ibrance

CDK4/6 inhibitor + chemotherapy: Carboplatin + Palbociclib; CDK4/6 inhibitor + chemotherapy: Paclitaxel + Palbociclib; CDK4/6 inhibitor alone: Palbociclib (IMP)

Paclitaxel DRUG

Chemotherapy

CDK4/6 inhibitor + chemotherapy: Paclitaxel + Palbociclib; Chemotherapy alone: Paclitaxel

Carboplatin DRUG

Chemotherapy

CDK4/6 inhibitor + chemotherapy: Carboplatin + Palbociclib; Chemotherapy alone: Carboplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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;

Sponsors & Collaborators

• Medical University of Gdansk: lead

Study Sites (6)

Wielkopolskie Centrum Onkologii im. Marii Skłodowskiej-Curie, Oddział Onkologii Klinicznej i Immunoonkologii z Pododdziałem Dziennym

Poznan, Greater Poland Voivodeship, 61 885 05 57, Poland

Location

Dolnośląskie Centrum Onkologii we Wrocławiu, Oddział Onkologii Klinicznej/Chemioterapii, Poradnia Chemioterapii; Leczenie Nowotworów Piersi

Wroclaw, Lower Silesian Voivodeship, 53-413, Poland

Location

Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie

Warsaw, Masovian Voivodeship, 22 546 20 00, Poland

Location

SP ZOZ Opolskie Centrum Onkologii im. Prof. Tadeusza Koszarowskiego

Opole, Opole Voivodeship, 45-061, Poland

Location

Uniwersyteckie Centrum Kliniczne, Klinika Onkologii i Radioterapii

Gdansk, Pomeranian Voivodeship, 80-952, Poland

Location

Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie, Państwowy Instytut Badawczy, Oddział w Gliwicach

Gliwice, Silesian Voivodeship, 44-102, Poland

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

palbociclib; Paclitaxel; Carboplatin

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes

Central Study Contacts

Elżbieta Senkus-Konefka, MD, PhD

CONTACT

58 584 4482; elzbieta.senkus-konefka@gumed.edu.pl

Monika Puchowska, MSc

CONTACT

58 349 1885; monika.puchowska@gumed.edu.pl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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)

Study Record Dates

• First Submitted: September 23, 2021
• First Posted: October 5, 2021
• Study Start: January 1, 2022
• Primary Completion: January 1, 2025
• Study Completion (Estimated): December 6, 2026
• Last Updated: October 5, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

PL (6)