Palbociclib and Binimetinib in Advanced Triple Negative Breast Cancer

  • STATUS
    Recruiting
  • End date
    Aug 1, 2023
  • participants needed
    25
  • sponsor
    Fundacion Oncosur
Updated on 16 September 2021
triple negative breast cancer
palbociclib
BRCA1
BRCA2
mammogram

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.

Details
Condition Adverse Effects, Drugs, Chronic Shoulder Pain, Vaginal Atrophy, Pediatric Health, Chronic Diarrhea, Breast Cancer - HER2 Positive, Peripheral Arterial Occlusive Disease, Primary Immunodeficiency, Recurrent Respiratory Papillomatosis, Skin Wounds, Breast Cancer, Razor Bumps (Pseudofolliculitis Barbae), Diet and Nutrition, Injection Port, Brain Function, Metastatic Triple-Negative Breast Cancer, Triple Negative Breast Cancer, Near-Sighted Corrective Surgery, Anal Dysplasia
Treatment Combination, Palbociclib + Binimetinib
Clinical Study IdentifierNCT04494958
SponsorFundacion Oncosur
Last Modified on16 September 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Women >18 years-old
Diagnostic of metastatic or locally advanced non-resectable TNBC
Patient must have received a minimum of one and a maximum of two treatment lines for metastatic TNBC. 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
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

Exclusion Criteria

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
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
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