Trial record 1 of 1 for:
05554354
Testing the Use of Fulvestrant and Binimetinib Targeted Treatment for NF1 Mutation in Hormone Receptor-Positive Metastatic Breast Cancer (A ComboMATCH Treatment Trial)
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| ClinicalTrials.gov Identifier: NCT05554354 |
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Recruitment Status :
Recruiting
First Posted : September 26, 2022
Last Update Posted : May 1, 2024
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Sponsor:
National Cancer Institute (NCI)
Collaborator:
NRG Oncology
Information provided by (Responsible Party):
National Cancer Institute (NCI)
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Brief Summary:
This phase II ComboMATCH treatment trial compares the usual treatment alone (fulvestrant) to using binimetinib plus the usual treatment in patients with hormone receptor positive breast cancer that has spread from where it first started to other places in the body (metastatic) and has an NF1 genetic change. Fulvestrant is a hormonal therapy that binds to estrogen receptors in tumor cells, resulting in estrogen receptor destruction and decreased estrogen binding, which may inhibit the growth of estrogen-sensitive tumor cells. Binimetinib is a targeted therapy that may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. The addition of binimetinib to fulvestrant in breast cancers with an NF1 genetic change could increase the percentage of tumors that shrink as well as lengthen the time that the tumors remain stable (without progression) as compared to fulvestrant alone.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Anatomic Stage IV Breast Cancer AJCC v8 Metastatic HER2-Negative Breast Carcinoma Metastatic Hormone Receptor-Positive Breast Carcinoma | Drug: Binimetinib Procedure: Biopsy Procedure: Biospecimen Collection Procedure: Bone Scan Procedure: Computed Tomography Procedure: Echocardiography Drug: Fulvestrant Procedure: Magnetic Resonance Imaging Procedure: Multigated Acquisition Scan | Phase 2 |
Show detailed description
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 95 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Phase 2 Trial of Fulvestrant and Binimetinib in Patients With Hormone Receptor-Positive Metastatic Breast Cancer With Inactivating or Inferred Inactivating NF1 Alterations: A ComboMATCH Treatment Trial |
| Estimated Study Start Date : | May 29, 2024 |
| Estimated Primary Completion Date : | November 1, 2026 |
| Estimated Study Completion Date : | November 1, 2026 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: Cohort I (Arm I) (fulvestrant, binimetinib)
Patients receive fulvestrant IM on day 1 and day 15 of cycle 1 and day 1 of subsequent cycles and binimetinib PO BID on days 15 to 28 of cycle 1 and day 1 through 28 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo a CT, MRI, or bone scan, ECHO or MUGA, and tumor biopsy, as well as possible blood sample collection during screening and on study.
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Drug: Binimetinib
Given PO
Other Names:
Procedure: Biopsy Undergo tumor biopsy
Other Names:
Procedure: Biospecimen Collection Undergo blood sample collection
Other Names:
Procedure: Bone Scan Undergo bone scan
Other Name: Bone Scintigraphy Procedure: Computed Tomography Undergo CT scan
Other Names:
Procedure: Echocardiography Undergo ECHO
Other Name: EC Drug: Fulvestrant Given IM
Other Names:
Procedure: Magnetic Resonance Imaging Undergo MRI
Other Names:
Procedure: Multigated Acquisition Scan Undergo MUGA
Other Names:
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Active Comparator: Cohort I (Arm II)
Patients receive fulvestrant IM on day 1 and day 15 of cycle 1 and day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who progress on fulvestrant alone may migrate to cohort II if they meet the migration eligibility criteria. Patients not willing to migrate to cohort II will have further therapy at the investigator's discretion. Patients undergo a CT, MRI, or bone scan and tumor biopsy, as well as ECHO or MUGA and possible blood sample collection during screening and on study.
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Procedure: Biopsy
Undergo tumor biopsy
Other Names:
Procedure: Biospecimen Collection Undergo blood sample collection
Other Names:
Procedure: Bone Scan Undergo bone scan
Other Name: Bone Scintigraphy Procedure: Computed Tomography Undergo CT scan
Other Names:
Procedure: Echocardiography Undergo ECHO
Other Name: EC Drug: Fulvestrant Given IM
Other Names:
Procedure: Magnetic Resonance Imaging Undergo MRI
Other Names:
Procedure: Multigated Acquisition Scan Undergo MUGA
Other Names:
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Experimental: Cohort II (fulvestrant, binimetinib)
Patients receive fulvestrant IM on day 1 of each cycle and binimetinib PO BID on days 15-28 of cycle 1 and day 1 through 28 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo a CT, MRI, or bone scan, ECHO or MUGA and tumor biopsy, as well as possible blood sample collection during screening and on study.
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Drug: Binimetinib
Given PO
Other Names:
Procedure: Biopsy Undergo tumor biopsy
Other Names:
Procedure: Biospecimen Collection Undergo blood sample collection
Other Names:
Procedure: Bone Scan Undergo bone scan
Other Name: Bone Scintigraphy Procedure: Computed Tomography Undergo CT scan
Other Names:
Procedure: Echocardiography Undergo ECHO
Other Name: EC Drug: Fulvestrant Given IM
Other Names:
Procedure: Magnetic Resonance Imaging Undergo MRI
Other Names:
Procedure: Multigated Acquisition Scan Undergo MUGA
Other Names:
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Primary Outcome Measures :
- Progression free survival (PFS) (Cohort I) [ Time Frame: The duration between randomization and progression or death from all cause, whichever happens first, assessed up to 5 years ]PFS of the two study arms will be compared by log-rank test (1-sided, alpha=0.1). Kaplan-Meier plot will be provided. Hazard ratio (HR) and the corresponding 95% confidence interval (CI) will be estimated by Cox proportional model using treatment as covariate.
- Objective response rate (ORR) (Cohort II) [ Time Frame: Within 4 months of the start of treatment ]ORR is the percentage of patients who reaches a complete or partial response (defined by Response Evaluation Criteria in Solid Tumors [RECIST] version[v]1.1) within 4 months of the start of the treatment. ORR will be calculated as the proportion of patients achieved partial response (PR) or complete response (CR) within 4 months after the initiation of the treatment. ORR will be reported with corresponding 95% exact CI. Patients who have withdrawn from the study before any efficacy follow up are considered non-evaluable for clinical response and will be replaced.
Secondary Outcome Measures :
- ORR for each study arm (Cohort I) [ Time Frame: Any time after the start of the treatment, assessed up to 5 years ]ORR is the percentage of patients who reach a complete or partial response (defined by RECIST v1.1) any time after the start of the treatment. ORR for each study arm will be calculated with corresponding 95% exact CI. Fisher exact test will be used to compare the ORR of the two study arms.
- ORR (Cohort II) [ Time Frame: Any time after the start of the treatment, assessed up to 5 years ]ORR is the percentage of patients who reach a complete or partial response (defined by RECIST v1.1) any time after the start of the treatment.
- Clinical benefit rate [ Time Frame: Any time after the start of the treatment, assessed up to 5 years ]Defined as proportion of patients who achieved a CR, PR, or stable disease defined by RECIST criteria any time after the start of the treatment. Clinical benefit rate will be analyzed for each arm of cohort I and cohort II as described for ORR. ORR for each study arm will be calculated with corresponding 95% exact CI. Fisher exact test will be used to compare the ORR of the two study arms.
- PFS (Cohort II) [ Time Frame: The duration between randomization and progression or death from all cause, whichever happens first, assessed up to 5 years ]PFS for cohort II will be summarized using the Kaplan-Meier's method. Median PFS with corresponding 95% CI will be provided.
- Overall survival (OS) [ Time Frame: The duration between randomization and death of all causes, assessed up to 5 years ]OS for cohort I will be analyzed as described for PFS in cohort I and OS for cohort II will be analyzed as described for PFS in cohort II. PFS of the two study arms will be compared by log-rank test (1-sided, alpha=0.1). Kaplan-Meir plot will be provided. HR and the corresponding 95% CI will be estimated by Cox proportional model using treatment as covariate. PFS for Cohort 2 will be summarized using the Kaplan-Meir's method. Median PFS with corresponding 95% CI will be provided.
- Incidence of adverse events [ Time Frame: Up to 5 years ]The grade of toxicity measurement will follow Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The distribution by treatment group of the highest grade of each CTCAEs experienced by each patient categorized will be tabulated. The tabulations will also be reviewed on a semi-annual basis by the Data Monitoring Committee. These tabulations will include summaries by system organ class and summaries by term under each system organ class.
Other Outcome Measures:
- Analysis of integrated and exploratory biomarkers [ Time Frame: Up to 5 years ]A separate statistical analysis plan will be developed for the integrated and exploratory biomarker analysis. Concordance of diagnostic tumor mutation profile generated by the designated laboratory, the pre-treatment biopsy mutation profile, and the pre-treatment circulating tumor deoxyribonucleic acid mutation profile will be assessed. Details are provided in the statistical plan of the ComboMATCH Registration protocol.
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Patient must have enrolled onto EAY191 and must have been given a treatment assignment to ComboMATCH to EAY191-N2 based on the presence of an actionable mutation as defined in EAY191
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The patient must be enrolled on the ComboMATCH Master Registration Trial EAY191
- Note: Patients must fulfill all eligibility criteria outlined in the ComboMATCH Registration Trial EAY191 at the time of registration to EAY191-N2. This includes submission of next-generation sequencing (NGS) data from one of the National Cancer Institute (NCI) credentialed designated laboratories for all potential patients prior to treatment trial assignment. Copy number and allele frequency cutoff as per the Registration protocol
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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 Cancer Trial Support Unit (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 United States (U.S.), authorization permitting release of personal health information
- Age >= 18
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Histologically or cytologically confirmed invasive breast carcinoma
- Confirmed metastatic disease by either imaging or tissue diagnosis
- Measurable disease by Response Evaluation Criteria in Solid Tumors (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 estrogen receptor (ER) and/or progesterone receptor (PgR) positive assessed by current American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline recommendations for hormone receptor testing. Patients with >= 1% ER or PgR staining by immunohistochemistry (IHC) are considered positive
- The tumor must have been determined to be HER2-negative by current ASCO/CAP guidelines
- Prior use of CDK4/6 inhibitor(i) 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
- Absolute neutrophil count >= 1,500/mm^3
- Platelet count >= 100,000/ mm^3
- Hemoglobin level >= 10 g/dL
- Creatinine clearance (CrCL) of ≥ 30 mL/min by the Cockcroft-Gault formula
- Total bilirubin level =< institutional upper limit of normal
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be =< 5.0 x ULN
- For patients who will be assigned to Cohort 2 (fulvestrant-resistant), a left ventricular ejection fraction (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
- Human immunodeficiency virus (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
- PATIENTS WHO MIGRATE TO COHORT 2: Patient's willingness to migrate to Cohort 2 affirmed
- PATIENTS WHO MIGRATE TO COHORT 2: The patient must have an ECOG performance status of 0-2
- PATIENTS WHO MIGRATE TO COHORT 2: Absolute neutrophil count >= 1,500/mm^3
- PATIENTS WHO MIGRATE TO COHORT 2: Platelet count >= 100,000/ mm^3
- PATIENTS WHO MIGRATE TO COHORT 2: Hemoglobin level >= 10 g/dL
- PATIENTS WHO MIGRATE TO COHORT 2: Total bilirubin level =< institutional upper limit of normal (ULN)
- PATIENTS WHO MIGRATE TO COHORT 2: AST and ALT must be =< 5.0 x ULN
- PATIENTS WHO MIGRATE TO COHORT 2: Creatinine clearance (CrCL) of ≥30 mL/min by the Cockcroft-Gault formula
- PATIENTS WHO MIGRATE TO COHORT 2: 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)
- PATIENTS WHO MIGRATE TO COHORT 2: Pregnancy test according to institutional standards must be negative (for patients of childbearing potential only)
Exclusion Criteria:
- 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
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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
- Patients with baseline QT corrected for heart rate (QTc) > 500 ms, either induced by medication or congenital long QT syndrome will be excluded due to known side effects of binimetinib
- Nervous system disorder (paresthesia, peripheral motor neuropathy, or peripheral sensory neuropathy) >= grade 2
- 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
- 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
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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
- PATIENTS WHO MIGRATE TO COHORT 2: Not a candidate for binimetinib in the opinion of the treating investigator
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05554354
Locations
Show 182 study locations
Sponsors and Collaborators
National Cancer Institute (NCI)
NRG Oncology
Investigators
| Principal Investigator: | Bora Lim | CenterThe University of Texas MD Anderson Cancer Center |
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT05554354 |
| Other Study ID Numbers: |
NCI-2022-07265 NCI-2022-07265 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) EAY191-N2 ( Other Identifier: NRG Oncology ) EAY191-N2 ( Other Identifier: CTEP ) U10CA180868 ( U.S. NIH Grant/Contract ) |
| First Posted: | September 26, 2022 Key Record Dates |
| Last Update Posted: | May 1, 2024 |
| Last Verified: | April 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page. |
| URL: | https://grants.nih.gov/policy/sharing.htm |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | No |
Additional relevant MeSH terms:
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Carcinoma Breast Neoplasms Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Neoplasms by Site Breast Diseases Skin Diseases |
Fulvestrant Antineoplastic Agents, Hormonal Antineoplastic Agents Estrogen Receptor Antagonists Estrogen Antagonists Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs |