Palbociclib and Binimetinib in Advanced Triple Negative Breast Cancer

NCT04494958 | Completed Phase 1 Results

• 2 other identifiers: PALBOBIN2020-000930-16
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 8

Brief Summary

This study is an interventional, prospective, multicentric, single-arm, open label, phase Ib clinical trial. This study will be carried out in patients diagnosed of metastatic or locally advanced unresectable triple negative breast cancer with activation of ERK and/or CDK4/6 in which the following will be assesed: the overall response rate, the aggregation of antitumor effect depending on the different kinome profiles and the safety profile to the combination of palbociclib and binimetinib.

Conditions

Triple Negative Breast Cancer

Outcome Measures

Primary Outcomes (1)

• 3 Months Progression Free Survival. Probability That the Cancer Has Not Progressed at 3 Months Calculated With Kaplan Meier.

  Progression free survival (PFS) is defined as the time from the date of start treatment until objective tumor progression or death from any reason. Patients who have not progressed or died at the time of analysis will be censored at the time of the latest date of assessment from their last evaluable RECIST 1.1 assessment. Progression free survival at three months is provided.

  3 months

Secondary Outcomes (2)

• Progression Free Survival

  3 months

• Overall Response Rate

  1 year

Study Arms (1)

Palbociclib + Binimetinib

EXPERIMENTAL

Drug: Combination, Palbociclib + Binimetinib

Interventions

Combination, Palbociclib + Binimetinib DRUG

Patients will then start treatment with continuous oral binimetinib 45 mg/BID and palbociclib 100 mg daily, 21 days on / 7 days off, until disease progression. Study treatment will continue until disease progression. If treatment tolerance is good, after a full cycle patients will be allowed to escalate palbociclib to 125 mg, according to the study investigators' decision. Alternatively, patients with non tolerable grade 2 events will resume at 30 mg/BID of binimetinib upon recovery, maintaining palbociclib at 100 mg 21-on/7-off. Depending on the side-effects, in case of clear relationship with palbociclib is established, palbociclib -instead of binimetinib - will be reduced to 75 mg daily.

Palbociclib + Binimetinib

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: In this Case, gender is a eligibility criteria because it is a specific cancer in women.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women \>18 years-old.
• Diagnostic of metastatic or locally advanced non-resectable TNBC.
• Patient that have received at least one and up to two previous lines of therapy for metastatic TNBC and failed to last treatment. Previous treatments can be of any nature (chemotherapy, immunotherapy, antiangiogenics, experimental therapy, etc.).
• Women with known BRCA1/BRCA2 germline mutations must have received a platinum based treatment or treatment with a PARP inhibitor.
• Patient must have experienced disease progression to the previous treatment line according to the RECIST 1.1 or iRECIST criteria.
• Ability to understand and signing of the written patient information/informed consent form (PIS/ICF) for ERK and CDK4/6 testing. ERK and CDK4/6 testing will be performed centrally at CNIO.
• Ability to understand and signing the written PIS/ICF for study treatment eligibility. Signed informed consent form must be available before any studyspecific procedure for the respective study parts may begin.
• Positivity for ERK and/or CDK4/6, defined as showing an H-score above the top-quartile according to published definitions \[1\].
• ECOG performance status of 0-1.
• Evaluable disease according to RECIST 1.1 criteria.
• Life expectancy \>24 weeks.
• Adequate bone marrow, liver and renal function as assessed by laboratory requirements conducted within 7 days before first study drug administration:
• Absolute neutrophil count (ANC) ≥ 1.500/mm3 (without granulocyte colony-stimulating factor support within 2 weeks before the first study drug administration)
• Hemoglobin ≥ 9 g/dL (without transfusion or erythropoietin within 4 weeks before the first study drug administration)
• Platelet count ≥ 100.000/mm3 (without transfusion within 2 weeks before the first study drug administration)

You may not qualify if:

• Participants who have had chemotherapy, radiotherapy, or major surgery within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study.
• Patients that received during the metastatic disease setting any of the study drugs, palbociclib or binimetinib.
• Participants receiving any other study agents concurrently with the study drugs. Zoledronic acid or denosumab for bone metastases, started at least 15 days prior to enrollment are allowed.
• Participants with symptomatic brain metastases that require chronic steroids. Patients with a history of brain metastases are permitted to enroll as long as they have been treated, are off of steroids, and have been stable for a minimum of one month on imaging.
• Irradiation of single lesions in the last 28 days prior to trial recruitment, if it is the only location of the disease and it has not progressed. Patients with radiated single lesions that has progressed are allowed.
• Concurrent use of strong CYP3A4 inhibitors/inducers is prohibited due to drug-drug interactions with palbociclib. Moderate CYP3A4 inhibitors/inducers should be used with caution.
• Uncontrolled intercurrent illness including, but not limited to:
• ongoing or active infection requiring systemic treatment
• symptomatic congestive heart failure
• cardiac arrhythmia
• psychiatric illness/social situations that would limit compliance with study requirements
• hypertension, defined as systolic blood pressure \> 160 mmHg despite medical management
• myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting \< 6 months prior to screening
• History of QT syndrome, Brugada syndrome, known history of QTc prolongation, or Torsades de Pointes.
• History of Gilbert's syndrome.

Sponsors & Collaborators

• Fundacion Oncosur: lead
• Pfizer: collaborator
• Apices Soluciones S.L.: collaborator
• Pierre Fabre Ibérica, S.A.: collaborator

Study Sites (8)

Hospital Universitari Arnau de Vilanova de Lleida

Lleida, 25198, Spain

Location

Hospìtal Universitario de la Princesa

Madrid, 28006, Spain

Location

Hospital Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Clínico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital QuirónSalud Madrid

Madrid, 28223, Spain

Location

Hospital Universitario de Fuenlabrada

Madrid, 28942, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, 46010, Spain

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

palbociclib; binimetinib

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Juan Luis Sanz
• Organization: APICES

juanluis.sanz@apices.es

91 816 68 04

Study Officials

• Miguel Ángel Quintela-Fandino, MD

  Centro Nacional de Investigaciones Oncológicas

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: Prospective, multicentric, single-arm, open label, phase IB clinical trial.

Study Record Dates

• First Submitted: July 28, 2020
• First Posted: July 31, 2020
• Study Start: November 18, 2020
• Primary Completion: December 14, 2023
• Study Completion: December 14, 2023
• Last Updated: March 24, 2025
• Results First Posted: March 24, 2025

Record last verified: 2025-03

Locations

ES (8)