Encorafenib and Binimetinib With or Without Nivolumab in Treating Patients With Metastatic Radioiodine Refractory BRAF V600 Mutant Thyroid Cancer

  • STATUS
    Recruiting
  • End date
    Aug 1, 2024
  • participants needed
    40
  • sponsor
    Providence Health & Services
Updated on 4 October 2022

Summary

This phase II trial studies how well encorafenib and binimetinib given with or without nivolumab works in treating patients with BRAF V600 mutation positive thyroid cancer that has spread to other places in the body (metastatic) and does not respond to radioiodine treatment (refractory). Encorafenib and binimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body?s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. The trial aims to find out if the combination of encorafenib and binimetinib, with and without study nivolumab, is a safe and effective way to treat metastatic radioiodine refractory thyroid cancer.

Description

PRIMARY OBJECTIVES:

I. To assess the overall rate of response among study participants treated with the combination of encorafenib and binimetinib, with or without nivolumab.

SECONDARY OBJECTIVES:

I. To assess the progression-free survival (PFS) among study participants treated with the combination of encorafenib and binimetinib with or without nivolumab.

II. To assess the overall survival (OS) among study participants treated with the combination of encorafenib and binimetinib with or without nivolumab.

III. To evaluate the duration of response (DOR). IV. To evaluate the safety and tolerability of study participants treated with the combination of encorafenib and binimetinib with or without nivolumab.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive encorafenib orally (PO) once daily (QD) and binimetinib PO twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive encorafenib PO QD and binimetinib PO BID as in arm I. Patients also receive nivolumab intravenously (IV) over 30 minutes on day 1. Cycles with nivolumab repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment patients are followed up at 30 days and then every 6 months for up to 12 months.

Details
Condition BRAF NP_004324.2:p.V600M, BRAF V600E Mutation Present, Metastatic Thyroid Gland Carcinoma, Refractory Thyroid Gland Carcinoma, Stage IV Differentiated Thyroid Gland Carcinoma AJCC v8, Stage IVA Differentiated Thyroid Gland Carcinoma AJCC v8, Stage IVB Differentiated Thyroid Gland Carcinoma AJCC v8
Treatment Nivolumab, Binimetinib, Encorafenib
Clinical Study IdentifierNCT04061980
SponsorProvidence Health & Services
Last Modified on4 October 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent document
Histologically (or cytologically) confirmed diagnosis of metastatic, radioiodine (RAI) refractory, BRAFV600E/M mutant differentiated thyroid cancer (DTC)
Note: RAI refractoriness is defined as
The absence of uptake of RAI on either a low-dose diagnostic whole body scan, or a post-treatment RAI scan in measurable lesions
Radiographic progression of disease within 12 months of the last course of RAI treatment, or
Having a cumulative lifetime administered dose of > 600 mCi of RAI
Measurable disease meeting the following criteria and confirmed by radiography review
At least 1 lesion of >= 1.0 cm in the longest diameter for a non-lymph node or > 1.5 cm in the short-axis diameter for a lymph node metastasis that is serially measurable according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 using computed tomography/magnetic resonance imaging (CT/MRI). If there is only 1 target lesion and it is a non-lymph node, it should have a longest diameter of >= 1.5 cm
Lesions that have had external beam radiotherapy or locoregional therapies such as radiofrequency (RF) ablation must show evidence of progressive disease based on RECIST 1.1 to be deemed a target lesion
Eastern Cooperative Oncology Group (ECOG) performance status =< 1
Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
Hemoglobin (Hgb) >= 9 g/dL
Platelets (PLT) >= 75 x 10^9/L
Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN); participants with liver metastases =< 5 x ULN
Total bilirubin =< 1.5 x ULN
Note: Individuals who have a total bilirubin level > 1.5 x ULN will be allowed if their indirect bilirubin level is =< 1.5 x ULN (i.e., participants with suspected or known diagnosis of Gilbert?s syndrome)
Serum creatinine =< 1.5 x ULN, or calculated creatinine clearance (determined as per
Left ventricular ejection fraction (LVEF) >= 50% as determined by a multigated acquisition (MUGA) scan or echocardiogram
Cockcroft-Gault) >= 40 mL/min at screening
Triplicate average baseline corrected QT (QTc) interval =< 480 ms
Participants of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 72 hours prior to the start of assigned study intervention
Participants of child-bearing potential agree to use highly effective methods of contraception starting with the first dose of assigned study intervention through 6 months after the last dose of study therapy
Participants of childbearing potential are those who are not proven postmenopausal. Postmenopausal is defined as any of the following
Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments
Luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the post-menopausal range for women under 50
Radiation-induced oophorectomy with last menses > 1 year ago
Chemotherapy-induced menopause with > 1 year interval since last menses
Surgical sterilization (bilateral oophorectomy or hysterectomy)
Male participants must agree to use an adequate method of contraception starting with
the first dose of study therapy through 6 months after the last dose of study
therapy

Exclusion Criteria

Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational agent/device within 4 weeks of first dose of study intervention
Note: Individuals in the follow-up phase of a prior investigational study may participate as long as it has been 4 weeks since last dose of the previous investigational agent of device
Prior treatment with selective/potent BRAF/MEK inhibitors including vemurafenib, dabrafenib, encorafenib, selumetinib, trametinib, cobimetinib, binimetinib
Note: Prior therapy with oral multikinase inhibitors (e.g., lenvatinib, sorafenib, cabozantinib, pazopanib, sunitinib, etc.) remain eligible for study participation
Participants with active, known, or suspected autoimmune disease. Participants with
Participants with a condition requiring systemic treatment with either corticosteroids (>= 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids are permitted in the absence of active autoimmune disease
type I diabetes mellitus, residual hypothyroidism due to autoimmune
History of allergy or hypersensitivity to any monoclonal antibody
thyroiditis only requiring hormone replacement, skin disorders (such as
vitiligo, psoriasis, or alopecia) not requiring systemic treatment are
History or current evidence of retinal vein occlusion (RVO) or current risk factors to RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes); history of retinal degenerative disease
permitted to enroll
Previous or concurrent malignancy within 3 years of study entry, with the following
exceptions
Adequately treated basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in-situ of the cervix, or other noninvasive or indolent malignancy; OR
Prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4
Other solid tumors treated curatively in which the expected rate of recurrence within 5 years is < 5%
antibody (including ipilimumab or any other antibody or drug specifically
History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) < 6 months prior to screening
targeting T cell co-stimulation or immune checkpoint pathways)
Symptomatic congestive heart failure (i.e. grade 2 or higher), history or current evidence of clinically significant cardiac arrhythmia and/or conduction abnormality < 6 months prior to screening. Exceptions include asymptomatic/well-controlled atrial fibrillation/flutter or paroxysmal supraventricular tachycardia
Uncontrolled hypertension defined as persistent elevation of systolic blood pressure >= 150 mmHg or diastolic blood pressure >= 100 mmHg, despite medical therapy
Note: Individuals with either deep vein thrombosis or pulmonary emboli that does not result in hemodynamic instability are allowed to enroll as long as they are on a stable dose of anticoagulants for at least 4 weeks
Note: Individuals with thromboembolic events related to indwelling catheters or other procedures may be enrolled
Known history of acute or chronic pancreatitis
Impaired gastrointestinal function or disease that may significantly alter the absorption of encorafenib or binimetinib (e.g., uncontrolled vomiting or malabsorption syndrome)
Impaired cardiovascular function or clinically significant cardiovascular diseases
Concurrent neuromuscular disorder that is associated with the potential of elevated creatine kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy)
including any of the following
Current use of a prohibited medication (including herbal medications, supplements, or foods), as described, or use of a prohibited medication =< 1 week prior to the start of study treatment
Any other condition that would, in the investigator?s judgment, contraindicate an individual?s participation in the clinical study due to safety concerns or compliance with clinical study procedures, e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, social/ psychological issues, etc
Participants who have undergone major surgery (e.g., intracranial, intrathoracic, or intra-abdominal surgery) =< 3 weeks prior to starting study drug or who have not recovered from side effects of such procedure
Participants that are pregnant or nursing (lactating)
History of thromboembolic or cerebrovascular events =< 12 weeks prior to the first
Prisoners or individuals who are involuntarily incarcerated
dose of study treatment. Examples include transient ischemic attacks
Medical, psychiatric, cognitive or other conditions that may compromise the participant?s ability to understand the patient information, give informed consent, comply with the study protocol or complete the study
cerebrovascular accidents, hemodynamically significant (i.e., massive or sub-
massive) deep vein thrombosis or pulmonary emboli
Known positive serology for HIV (human immunodeficiency virus), active hepatitis B
and/or active hepatitis C infection
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