Triple Negative Breast CancerPhase 1/2PALBOBINNCT04494958

Palbociclib and Binimetinib in Advanced Triple Negative Breast Cancer

A Phase 1/2 study testing Combination, Palbociclib + Binimetinib in people with Triple Negative Breast Cancer, run by Fundacion Oncosur at 8 sites in Spain.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 18 years and older, women only
Conditions the study is for: Triple Negative Breast Cancer
What is being tested?: Combination, Palbociclib + Binimetinib
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 24 participants
Where: 8 sitesSpain
Study dates: 18 Nov 2020to 14 Dec 2023
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
Women only
No healthy volunteers
Adult, Older adult

Who may be able to join

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.
Availability of tumor tissue for ERK and CDK4/6 testing is mandatory prior to study inclusion, preferably obtained after last treatment or the most recent sample as possible (from metastatic site or first diagnosis according to sample availability). If the patient has not a tumor sample available prior to study inclusion, the patient will not be allowed to participate in the study.

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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)
Total bilirubin ≤ 2 X the upper limit of normal (ULN).
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 X ULN (≤ 5 times ULN for patients with liver metastases)
Glomerular filtration rate (GFR) > 50 mL/min/1.73 m2 according to the modification of diet in renal disease (MDRD) abbreviated formula.
Patients must have recovered to ≤ Grade 1 in terms of toxicity from prior treatments (excluding neuropathy which can be ≤ Grade 2, and alopecia).
Patients must be able to take oral medications.
Patients must have adequate cardiac function, defined as:
Left ventricular ejection fraction (LVEF) > 50% as determined by echocardiogram or multigated acquisition scan (MUGA).
QTc < 480 msec.
Negative serum pregnancy test in women of childbearing potential (performed within 7 days before the first treatment). Negative results must be available before the first study drug administration. Pregnancy test will not be performed in postmenopausal women.
Women of reproductive potential must agree to use adequate contraception when sexually active. This applies for the time period since the signature of the informed consent form and until at least 1 month after the last study drug administration. The definition of adequate contraception will be based on the judgment of the investigator and on local requirements. Acceptable methods of contraception include, but are not limited to, (i) condoms (male or female) with or without a spermicidal agent; (ii) diaphragm or cervical cap with spermicide; (iii) intra-uterine device; (iv) hormone-based contraception.Zoledronic acid or denosumab started prior to trial registration is allowed, but in case they are required after initiation of trial procedures, adequate justification is required.

Who cannot join

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.

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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.
History of neuromuscular disorders that are associated with elevated CK (e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy).
Previous or concurrent cancer except:
cervical carcinoma in situ
treated basal-cell carcinoma or squamous cell skin cancer c. any other cancer curatively treated > 3 years before the first study drug administration
Malabsorption syndrome or uncontrolled nausea, vomiting, or diarrhea that may interfere with the absorption of oral study medication in the opinion of the investigator.
Pregnant women or breast-feeding.
Known HIV-positive individuals on combination antiretroviral therapy.
Active hepatitis B virus (HBV; chronic or acute; defined as having a known positive hepatitis B surface antigen [HBsAg] test at the time of screening) or hepatitis C infection requiring treatment.
Patients with past HBV infection or resolved HBV infection (defined as the presence of hepatitis B core antibody [HBcAb] and absence of HBsAg) are eligible if HBV DNA is negative.
Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
Any condition that in the opinion of the investigator would interfere with evaluation of study treatment or interpretation of patient safety or study results, or inability to comply with the study and follow-up procedures.
Participation in another clinical study with investigational medicinal products within 4 weeks before the first study drug administration.
Clinically active infections within 2 weeks before the first study drug administration.
Treatment with therapeutic oral or i.v. antibiotics within 2 weeks before the first study drug administration. Patients receiving prophylactic antibiotics (e.g. for prevention of a urinary tract infection or to prevent chronic obstructive pulmonary disease exacerbation) are eligible.
Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation.
Current diagnosis of any retinal disorders including retinal detachment, retinal pigment epithelial detachment (RPED), serous retinopathy or retinal vein occlusion or risk factors for RVO (e.g., uncontrolled glaucoma or history of hyperviscosity or hypercoagulability syndrome).
Peripheral sensory neuropathy of CTCAE v.5.0 Grade 2 or higher
Major surgery, open biopsy or significant traumatic injury within 4 weeks before the first study drug administration (central line surgery is not considered major surgery).
Renal failure requiring peritoneal dialysis or hemodialysis.
Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results.

Trial locations and contacts

8 sites in 1 country.

City, postcode or hospital

8 sites in 1 country

Spain8 sites

Hospital Universitari Arnau de Vilanova de Lleida
Lleida, 25198
Hospìtal Universitario de la Princesa
Madrid, 28006
Hospital Ramon y Cajal
Madrid, 28034
Hospital Clínico San Carlos
Madrid, 28040
Hospital Universitario 12 de Octubre
Madrid, 28041
Hospital QuirónSalud Madrid
Madrid, 28223
Hospital Universitario de Fuenlabrada
Madrid, 28942
Hospital Clínico Universitario de Valencia
Valencia, 46010

Other trials in Spain

About this study

Official title: Phase IB Clinical Trial of Palbociclib and Binimetinib in Advanced Triple Negative Breast Cancer With Hyperactivation of ERK and/or CDK4/6

Conditions: Triple Negative Breast Cancer
Being tested: Combination, Palbociclib + Binimetinib
Medical subject headings: Triple Negative Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Combination, Palbociclib + BinimetinibDrug
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.

Study groups in NCT04494958
Study group	Role	What they receive
Palbociclib + Binimetinib	Experimental	Not described Receives: Drug: Combination, Palbociclib + Binimetinib

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 3 months

Secondary outcomes (2)

Progression Free Survival
Time from the date of first dose of study treatment to the date of progression or death (from any cause).
Measured: 3 months
Overall Response Rate
Percentage of patients that achieve complete response or partial response according to RECIST 1.1 criteria
Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

18 Nov 202014 Dec 2023

First posted31 Jul 2020
Study start18 Nov 2020
Primary completion14 Dec 2023
Study completion14 Dec 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Triple Negative Breast CancerStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Model description: Prospective, multicentric, single-arm, open label, phase IB clinical trial.
Masking: None (open label)
Enrolment: 24 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04494958
Sponsor's protocol ID: PALBOBIN
Other IDs: 2020-000930-16
Acronym: PALBOBIN
Status last verified: Mar 2025
First submitted: 28 Jul 2020
Last updated: 24 Mar 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

Publications

Manso L, Sanchez-Bayona R, Guerra JA, Cortes-Salgado A, Cejalvo JM, Garcia-Saenz JA, Morales S, Gonzalez-Cortijo L, Mouron S, Bueno MJ, Garma LD, Quintela-Fandino M. A Phase IB Study of Binimetinib and Palbociclib in Molecularly Selected Advanced Triple-Negative Breast Cancer. Cancer Res Commun. 2025 Sep 1;5(9):1728-1737. doi: 10.1158/2767-9764.CRC-25-0428.
PubMed 40928353

Study at a glance

From the registry record, last updated by the sponsor on 24 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase IB Clinical Trial of Palbociclib and Binimetinib in Advanced Triple Negative Breast Cancer With Hyperactivation of ERK and/or CDK4/6
ClinicalTrials.gov ID: NCT04494958
Acronym / sponsor ID: PALBOBIN / PALBOBIN
Conditions: Triple Negative Breast Cancer
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 24 participants (actual)
Lead sponsor: Fundacion OncosurResearch network
Collaborators: Pfizer, Apices Soluciones S.L., Pierre Fabre Ibérica, S.A.
Study start: 18 Nov 2020 (actual)
Primary completion: 14 Dec 2023 (actual)
Study completion: 14 Dec 2023 (actual)
First posted: 31 Jul 2020 (actual)
Results: Posted 24 Mar 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
Model description: Prospective, multicentric, single-arm, open label, phase IB clinical trial.

Arm	Type	Receives
Palbociclib + Binimetinib	Experimental	Drug: Combination, Palbociclib + Binimetinib

Who may qualify

Ages: 18 years and older
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (26 listed)

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.

Key exclusion criteria (35 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Combination, Palbociclib + BinimetinibPatients 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.	Drug	Palbociclib + Binimetinib

Primary outcome

3 Months Progression Free Survival. Probability That the Cancer Has Not Progressed at 3 Months Calculated With Kaplan Meier.
Time frame: 3 months
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.

2 secondary outcomes

Progression Free Survival
Time frame: 3 months
Overall Response Rate
Time frame: 1 year

Results and safety

Results posted to the registry on 24 Mar 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Palbociclib + Binimetinib	24	24

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

Time frame: 3 months. Number (95% Confidence Interval). Unit: perceent probability at 3 months

Measure	Palbociclib + Binimetinib n = 19
Value	15.8 (0.0 to 32.2)

Population analysed: All patients includeed in the study that received at least one dose of study treatment and have at least one evaluation visit after received the first dose of treatment.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: All adverse events that occur during the period comprehended from the start of study treatment to 30 days after last dose of the investigational products were recorded, an average of 3 months.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Palbociclib + Binimetinib	4 of 24 (16.7%)	24 of 24 (100%)	9 of 24

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 40928353Manso L, Sanchez-Bayona R, Guerra JA, Cortes-Salgado A, Cejalvo JM, Garcia-Saenz JA, Morales S, Gonzalez-Cortijo L, Mouron S, Bueno MJ, Garma LD, Quintela-Fandino M. A Phase IB Study of Binimetinib and Palbociclib in Molecularly Selected Advanced Triple-Negative Breast Cancer. Cancer Res Commun. 2025 Sep 1;5(9):1728-1737. doi: 10.1158/2767-9764.CRC-25-0428.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Miguel Ángel Quintela-Fandino, MD principal investigator

Centro Nacional de Investigaciones Oncológicas

8 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Combination, Palbociclib + Binimetinib in people with Triple Negative Breast Cancer, run by Fundacion Oncosur at 8 sites in Spain.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

3 Months Progression Free Survival. Probability That the Cancer Has Not Progressed at 3 Months Calculated With Kaplan Meier. (time frame: 3 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04494958, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2025.