This study is currently recruiting participants.
Number
002059-C
Sponsoring Institute
National Cancer Institute (NCI)
Recruitment Detail
Type: Participants currently recruited/enrolled Gender: Male & Female Min Age: 18 Years Max Age: 120 Years
Referral Letter Required
No
Population Exclusion(s)
Children;Pregnant Women
Keywords
Combination Therapy; Targeted Therapy; MEK Inhibitor; Metastatic Breast Cancer; Ras-MAPK Pathway
Recruitment Keyword(s)
None
Condition(s)
Breast Neoplasms; Breast Neoplasms, Hormone-Dependent; Neoplasm Metastasis; Hormone-Dependent Neoplasms; MAP Kinase Signaling System
Investigational Drug(s)
Fulvestrant Binimetinib
Investigational Device(s)
Intervention(s)
Drug: Fulvestrant Drug: Binimetinib
Supporting Site
National Cancer Institute
About 80% of breast cancers are hormone receptor (HR) positive. Treatments that target these hormone receptors generally get good results. But cancers often develop resistance to these treatments. And breast cancers that also have a mutation in the NF1 gene are more likely to return after treatment and spread to other tissues.
Objective:
To test a study drug (binimetinib), combined with the usual treatment (fulvestrant), in people with breast cancer that has an NF1 gene mutation.
Eligibility:
People aged 18 and older who are enrolled in the ComboMATCH protocol. They must have breast cancer that (1) has spread beyond the breast tissue, (2) is HR-positive, and (3) has a change in the NF1 gene.
Design:
Participants will be screened. They will have blood tests. They will provide a tissue sample (biopsy) of their tumor. If a recent sample is not available, a new biopsy may be done. They may have a test of their heart function.
All participants will be treated with fulvestrant. Fulvestrant is given as an injection into the muscle. Participants will receive the injection on days 1 to 15 of their first 28-day treatment cycle. After that, they will receive the injection on day 1 of each 28-day cycle.
Binimetinib is a pill taken by mouth. Some participants will take binimetinib 2 times a day for 28 days.
Participants will remain on the treatment as long as the drugs are helping them.
After treatment ends, participants will have follow-up visits every 6 months for up to 5 years. New biopsies and blood may be collected after treatment ends.
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INCLUSION CRITERIA: A patient cannot be considered eligible for this study unless ALL of the following conditions are met. A ComboMATCH Treatment Trial EAY191 Eligibility Criteria -The patient must be enrolled on the ComboMATCH Master Registration Trial EAY191. Note: Patients must fulfill all eligibility criteria of the ComboMATCH Registration Trial EAY191 at the time of registration to EAY191-N2. This includes submission of NGS data from one of the NCI credentialed Designated laboratories for all potential patients prior to treatment trial assignment. Copy number and allele frequency cutoff as per the Registration Protocol. -Patients must have disease that can be safely biopsied and agree to a pre-treatment biopsy or, if disease cannot be safely biopsied, have archival tissue available from within 12 months prior to the date of registration on the ComboMATCH Registration Trial (EAY191). Please note the current actionable marker of interest (aMOI)/actionable alteration list for this treatment trial can be found on the CTSU ComboMATCH Registration Protocol page. Please note novel/Dynamic aMOI can be submitted for review per the process described in the ComboMATCH Registration Protocol. A ComboMATCH Treatment Trial EAY191-N2 Eligibility Criteria -The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the U.S., authorization permitting release of personal health information. -Age >= 18. -ECOG performance status 0-2. -Histologically or cytologically confirmed invasive breast carcinoma. -Confirmed metastatic disease by either imaging or tissue diagnosis. -Measurable disease by RECIST 1.1 and one additional lesion that can be biopsied (primary, metastatic both allowed). -Patients must have inactivating or inferred inactivating NF1 alterations detected in tumor as determined by the ComboMATCH screening assessment. -The tumor must have been determined to be ER and/or PgR positive assessed by current ASCO/CAP Guideline Recommendations for hormone receptor testing. Patients with >= 1% ER or PgR staining by IHC are considered positive. -The tumor must have been determined to be HER2-negative by current ASCO/CAP guidelines. -Prior therapy: --Prior use of CDK4/6i is required. --Prior use of fulvestrant regardless of duration.is allowed and will determine treatment assignment. --Up to one line of chemotherapy in metastatic setting is allowed. -Adequate hematologic function defined as follows: --Absolute neutrophil count >= 1,500/mm^3 --Platelet count >= 100,000/ mm^3 --Hemoglobin level >= 10 g/dL -Adequate renal function defined as: Creatinine clearance (CrCL) of >= 30 mL/min by the Cockcroft-Gault formula. CrCl (mL/min) = [140 age (years)] x weight (kg)/72 x creatinine (mg / dL) (x 0.85 for female patients} -Adequate hepatic function defined as follows: --Total bilirubin level <= institutional upper limit of normal. --AST and ALT must be <= 5.0 x ULN. -For patients who will be assigned to Cohort 2 (fulvestrant-resistant), a LVEF assessment must be performed within 12 weeks prior to registration. The LVEF must be >= 50% regardless of the cardiac imaging facility s lower limit of normal. (LVEF assessment performed by echocardiogram is preferred; however, MUGA scan may be substituted based on institutional/situational preferences.) -Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. -HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial. Eligibility Criteria for Cohort 1, Treatment Regimen 2 Patients who Migrate to Cohort 2 -Cohort Migration --Patients treated with control treatment fulvestrant who experience disease progression may be eligible to migrate to Cohort 2 and receive combination treatment with binimetinib and fulvestrant. Patients who choose to do so must meet laboratory values and performance status requirements below and should begin treatment within 28 days. -Patient s willingness to migrate to Cohort 2 affirmed. -The patient must have an ECOG performance status of 0-2. -Adequate hematologic function defined as follows: --Absolute neutrophil count >= 1,500/mm^3 --Platelet count >= 100,000/ mm^3 --Hemoglobin level >= 10 g/dL -Adequate hepatic function defined as follows: --Total bilirubin level <= institutional upper limit of normal (ULN). --AST and ALT must be <= 5.0 x ULN. -Adequate renal function defined as: Creatinine clearance (CrCL) of >=30 mL/min by the Cockcroft-Gault formula. CrCl (mL/min) = [140 age (years)] x weight (kg)/72 x creatinine (mg / dL) {x 0.85 for female patients} -A LVEF performed within the last 3 months must be >= 50% regardless of the cardiac imaging facility s lower limit of normal. (LVEF assessment performed by echocardiogram is preferred; however, MUGA scan may be substituted based on institutional/situational preferences). -Pregnancy test according to institutional standards must be negative (for patients of childbearing potential only). EXCLUSION CRITERIA: Patients with any of the following conditions are NOT eligible for this study. -Concurrent anticancer therapy. -Active autoimmune disease requiring systemic treatment within the past 3 months, documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. -Active brain metastasis. Brain metastases that have been stable for at least 1 month after completion of treatment are not an exclusion criterion. -History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment/central serous, chorioretinopathy (CSCR), retinal vein occlusion (RVO), or neovascular macular degeneration. -Patients will be excluded if they currently have the following risk factors for RVO that are documented prior to the enrollment: --Known uncontrolled glaucoma with intra-ocular pressures >= 21 mmHg. --Known serum cholesterol >= Grade 2. --Known hypertriglyceridemia >= Grade 2. --Known hyperglycemia (fasting) >= Grade 2. -Cardiac history: --Patients with baseline QTc > 500 ms, either induced by medication or congenital long QT syndrome will be excluded due to known side effects of binimetinib. --Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better. -Nervous system disorder (paresthesia, peripheral motor neuropathy, or peripheral sensory neuropathy) >= Grade 2. -Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications. -Other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements or interfere with interpretation of study results. -Pregnancy or lactation at the time of registration or intention to become pregnant during the study. (Note: Pregnancy testing according to institutional standards for patients of childbearing potential.) --For binimetinib, highly effective contraception should be used for at least 30 days after the last dose, and patients should not breastfeed for 3 days after the last dose. --For fulvestrant, highly effective contraception should be used for 1 year after the last dose, and patients should not breastfeed for 1 year after the last dose. -Use of any investigational product within 30 days prior to study entry. Ineligibility Criteria for Cohort 1, Treatment Regimen 2 Patients who Migrate to Cohort 2 -Not a candidate for binimetinib in the opinion of the treating investigator.
A patient cannot be considered eligible for this study unless ALL of the following conditions are met.
A ComboMATCH Treatment Trial EAY191 Eligibility Criteria
-The patient must be enrolled on the ComboMATCH Master Registration Trial EAY191.
Note: Patients must fulfill all eligibility criteria of the ComboMATCH Registration Trial EAY191 at the time of registration to EAY191-N2. This includes submission of NGS data from one of the NCI credentialed Designated laboratories for all potential patients prior to treatment trial assignment. Copy number and allele frequency cutoff as per the Registration Protocol.
-Patients must have disease that can be safely biopsied and agree to a pre-treatment biopsy or, if disease cannot be safely biopsied, have archival tissue available from within 12 months prior to the date of registration on the ComboMATCH Registration Trial (EAY191).
Please note the current actionable marker of interest (aMOI)/actionable alteration list for this treatment trial can be found on the CTSU ComboMATCH Registration Protocol page.
Please note novel/Dynamic aMOI can be submitted for review per the process described in the ComboMATCH Registration Protocol.
A ComboMATCH Treatment Trial EAY191-N2 Eligibility Criteria
-The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the U.S., authorization permitting release of personal health information.
-Age >= 18.
-ECOG performance status 0-2.
-Histologically or cytologically confirmed invasive breast carcinoma.
-Confirmed metastatic disease by either imaging or tissue diagnosis.
-Measurable disease by RECIST 1.1 and one additional lesion that can be biopsied (primary, metastatic both allowed).
-Patients must have inactivating or inferred inactivating NF1 alterations detected in tumor as determined by the ComboMATCH screening assessment.
-The tumor must have been determined to be ER and/or PgR positive assessed by current ASCO/CAP Guideline Recommendations for hormone receptor testing. Patients with >= 1% ER or PgR staining by IHC are considered positive.
-The tumor must have been determined to be HER2-negative by current ASCO/CAP guidelines.
-Prior therapy:
--Prior use of CDK4/6i is required.
--Prior use of fulvestrant regardless of duration.is allowed and will determine treatment assignment.
--Up to one line of chemotherapy in metastatic setting is allowed.
-Adequate hematologic function defined as follows:
--Absolute neutrophil count >= 1,500/mm^3
--Platelet count >= 100,000/ mm^3
--Hemoglobin level >= 10 g/dL
-Adequate renal function defined as:
Creatinine clearance (CrCL) of >= 30 mL/min by the Cockcroft-Gault formula.
CrCl (mL/min) = [140 age (years)] x weight (kg)/72 x creatinine (mg / dL) (x 0.85 for female patients}
-Adequate hepatic function defined as follows:
--Total bilirubin level <= institutional upper limit of normal.
--AST and ALT must be <= 5.0 x ULN.
-For patients who will be assigned to Cohort 2 (fulvestrant-resistant), a LVEF assessment must be performed within 12 weeks prior to registration. The LVEF must be >= 50% regardless of the cardiac imaging facility s lower limit of normal. (LVEF assessment performed by echocardiogram is preferred; however, MUGA scan may be substituted based on institutional/situational preferences.)
-Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
-HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial.
Eligibility Criteria for Cohort 1, Treatment Regimen 2 Patients who Migrate to Cohort 2
-Cohort Migration
--Patients treated with control treatment fulvestrant who experience disease progression may be eligible to migrate to Cohort 2 and receive combination treatment with binimetinib and fulvestrant. Patients who choose to do so must meet laboratory values and performance status requirements below and should begin treatment within 28 days.
-Patient s willingness to migrate to Cohort 2 affirmed.
-The patient must have an ECOG performance status of 0-2.
--Total bilirubin level <= institutional upper limit of normal (ULN).
Creatinine clearance (CrCL) of >=30 mL/min by the Cockcroft-Gault formula.
CrCl (mL/min) = [140 age (years)] x weight (kg)/72 x creatinine (mg / dL) {x 0.85 for female patients}
-A LVEF performed within the last 3 months must be >= 50% regardless of the cardiac imaging facility s lower limit of normal. (LVEF assessment performed by echocardiogram is preferred; however, MUGA scan may be substituted based on institutional/situational preferences).
-Pregnancy test according to institutional standards must be negative (for patients of childbearing potential only).
EXCLUSION CRITERIA:
Patients with any of the following conditions are NOT eligible for this study.
-Concurrent anticancer therapy.
-Active autoimmune disease requiring systemic treatment within the past 3 months, documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents.
-Active brain metastasis. Brain metastases that have been stable for at least 1 month after completion of treatment are not an exclusion criterion.
-History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment/central serous, chorioretinopathy (CSCR), retinal vein occlusion (RVO), or neovascular macular degeneration.
-Patients will be excluded if they currently have the following risk factors for RVO that are documented prior to the enrollment:
--Known uncontrolled glaucoma with intra-ocular pressures >= 21 mmHg.
--Known serum cholesterol >= Grade 2.
--Known hypertriglyceridemia >= Grade 2.
--Known hyperglycemia (fasting) >= Grade 2.
-Cardiac history:
--Patients with baseline QTc > 500 ms, either induced by medication or congenital long QT syndrome will be excluded due to known side effects of binimetinib.
--Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.
-Nervous system disorder (paresthesia, peripheral motor neuropathy, or peripheral sensory neuropathy) >= Grade 2.
-Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications.
-Other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements or interfere with interpretation of study results.
-Pregnancy or lactation at the time of registration or intention to become pregnant during the study. (Note: Pregnancy testing according to institutional standards for patients of childbearing potential.)
--For binimetinib, highly effective contraception should be used for at least 30 days after the last dose, and patients should not breastfeed for 3 days after the last dose.
--For fulvestrant, highly effective contraception should be used for 1 year after the last dose, and patients should not breastfeed for 1 year after the last dose.
-Use of any investigational product within 30 days prior to study entry.
Ineligibility Criteria for Cohort 1, Treatment Regimen 2 Patients who Migrate to Cohort 2
-Not a candidate for binimetinib in the opinion of the treating investigator.
Principal Investigator
Referral Contact
For more information: