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Trial record 1 of 1 for:    NCT04494958
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Palbociclib and Binimetinib in Advanced Triple Negative Breast Cancer (PALBOBIN)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04494958
Recruitment Status : Recruiting
First Posted : July 31, 2020
Last Update Posted : December 17, 2020
Apices Soluciones S.L.
Pierre Fabre Ibérica, S.A.
Information provided by (Responsible Party):
Fundacion Oncosur

Tracking Information
First Submitted Date  ICMJE July 28, 2020
First Posted Date  ICMJE July 31, 2020
Last Update Posted Date December 17, 2020
Actual Study Start Date  ICMJE November 18, 2020
Estimated Primary Completion Date August 1, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 28, 2020)
Overral Response Rate [ Time Frame: 1 year ]
Percentage of patients that achieve complete response or partial response according to RECIST 1.1 criteria
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 28, 2020)
  • Progression Free survival [ Time Frame: 6 months ]
    Time from the date of first dose of study treatment to the date of progression or death (from any cause).
  • Incidence of treatment-Emergent Adverse Event [ Time Frame: 1 year ]
    Percentage of patients with each adverse event
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Palbociclib and Binimetinib in Advanced Triple Negative Breast Cancer
Official Title  ICMJE Phase IB Clinical Trial of Palbociclib and Binimetinib in Advanced Triple Negative Breast Cancer With Hyperactivation of ERK and/or CDK4/6
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
Prospective, multicentric, single-arm, open label, phase IB clinical trial.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Triple Negative Breast Cancer
Intervention  ICMJE Drug: Combination, Palbociclib + Binimetinib

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, according to the study investigators' decision. Alternatively, patients with nontolerable 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 Arms  ICMJE Experimental: Palbociclib + Binimetinib
Intervention: Drug: Combination, Palbociclib + Binimetinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 28, 2020)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 1, 2023
Estimated Primary Completion Date August 1, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Women >18 years-old.
  2. Diagnostic of metastatic or locally advanced non-resectable TNBC.
  3. Patient that have received 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.
  4. 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.
  5. 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.
  6. 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.
  7. Positivity for ERK and/or CDK4/6, defined as showing an H-score above the top-quartile according to published definitions [1].
  8. ECOG performance status of 0-1.
  9. Evaluable disease according to RECIST 1.1 criteria.
  10. Life expectancy >24 weeks.
  11. Adequate bone marrow, liver and renal function as assessed by laboratory requirements conducted within 7 days before first study drug administration:

    1. Absolute neutrophil count (ANC) ≥ 1.500/mm3 (without granulocyte colony-stimulating factor support within 2 weeks before the first study drug administration)
    2. Hemoglobin ≥ 9 g/dL (without transfusion or erythropoietin within 4 weeks before the first study drug administration)
    3. Platelet count ≥ 100.000/mm3 (without transfusion within 2 weeks before the first study drug administration)
    4. Total bilirubin ≤ 2 X the upper limit of normal (ULN).
    5. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 X ULN (≤ 5 times ULN for patients with liver metastases)
    6. Glomerular filtration rate (GFR) > 50 mL/min/1.73 m2 according to the modification of diet in renal disease (MDRD) abbreviated formula.
  12. Patients must have recovered to ≤ Grade 1 in terms of toxicity from prior treatments (excluding neuropathy which can be ≤ Grade 2, and alopecia).
  13. Patients must be able to take oral medications.
  14. Patients must have adequate cardiac function, defined as:

    1. Left ventricular ejection fraction (LVEF) > 50% as determined by echocardiogram or multigated acquisition scan (MUGA).
    2. QTc < 480 msec.
  15. 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.
  16. 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.

Exclusion Criteria:

  1. Participants who have had chemotherapy, radiotherapy, or major surgery within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study.
  2. Patients that received during the metastatic disease setting any of the study drugs, palbociclib or binimetinib.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. Uncontrolled intercurrent illness including, but not limited to:

    1. ongoing or active infection requiring systemic treatment
    2. symptomatic congestive heart failure
    3. cardiac arrhythmia
    4. psychiatric illness/social situations that would limit compliance with study requirements
    5. hypertension, defined as systolic blood pressure > 160 mmHg despite medical management
    6. myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting < 6 months prior to screening
  8. History of QT syndrome, Brugada syndrome, known history of QTc prolongation, or Torsades de Pointes.
  9. History of Gilbert's syndrome.
  10. History of neuromuscular disorders that are associated with elevated CK (e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy).
  11. Previous or concurrent cancer except:

    1. cervical carcinoma in situ
    2. treated basal-cell carcinoma or squamous cell skin cancer c. any other cancer curatively treated > 3 years before the first study drug administration
  12. Malabsorption syndrome or uncontrolled nausea, vomiting, or diarrhea that may interfere with the absorption of oral study medication in the opinion of the investigator.
  13. Pregnant women or breast-feeding.
  14. Known HIV-positive individuals on combination antiretroviral therapy.
  15. 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.

    1. 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.
    2. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  16. 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.
  17. Participation in another clinical study with investigational medicinal products within 4 weeks before the first study drug administration.
  18. Clinically active infections within 2 weeks before the first study drug administration.
  19. 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.
  20. Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation.
  21. 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).
  22. Peripheral sensory neuropathy of CTCAE v.5.0 Grade 2 or higher
  23. 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).
  24. Renal failure requiring peritoneal dialysis or hemodialysis.
  25. Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Gender Eligibility Description: In this Case, gender is a eligibility criteria because it is a specific cancer in women.
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Miguel Ángel Quintela-Fandino, MD +34917328000
Listed Location Countries  ICMJE Spain
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT04494958
Other Study ID Numbers  ICMJE PALBOBIN
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Fundacion Oncosur
Study Sponsor  ICMJE Fundacion Oncosur
Collaborators  ICMJE
  • Pfizer
  • Apices Soluciones S.L.
  • Pierre Fabre Ibérica, S.A.
Investigators  ICMJE
Principal Investigator: Miguel Ángel Quintela-Fandino, MD Centro Nacional de Investigaciones Oncológicas
PRS Account Fundacion Oncosur
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP