A Phase II Study of Cabozantinib in Combination With Cemiplimab (Cabo-Cemiplimab) Versus Cabozantinib Alone in Adolescents and Adults With Advanced Adrenocortical Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 48
- 试验地点
- 81
- 主要终点
- Progression free survival (PFS)
研究概览
简要总结
This phase II trial compares the effect of giving cabozantinib with or without cemiplimab in patients with adrenocortical cancer that has spread to nearby tissue or lymph nodes (locally advanced), and that cannot be removed by surgery (unresectable) or that has come back after a period of improvement (recurrent) or that has spread from where it first started (primary site) to other places in the body (metastatic). Cabozantinib is in a class of medications called tyrosine kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply, which may help keep cancer cells from growing. Immunotherapy with monoclonal antibodies, such as cemiplimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving cabozantinib with cemiplimab may kill more tumor cells in patients with locally advanced unresectable or recurrent/metastatic adrenocortical cancer.
详细描述
PRIMARY OBJECTIVE:
I. To determine whether the combination of cabozantinib plus cemiplimab (REGN2810) (Cabo-Cemiplimab [REGN2810]) improves progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) version (v.) 1.1 relative to cabozantinib alone in patients with locally advanced unresectable or recurrent/metastatic advanced adrenocortical cancer.
SECONDARY OBJECTIVES:
I. To assess tolerability and adverse events of Cabo-Cemiplimab (REGN2810) in advanced adrenocortical cancer (ACC) patients.
II. To assess objective response rate as per RECIST v 1.1. III. To assess duration of objective response, time to progression (TTP), and overall survival (OS) in ACC patients receiving Cabo-Cemiplimab (REGN2810).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •STEP 1: Patients must have documented histologically or cytologically confirmed adrenocortical carcinoma
- •STEP 1: Locally advanced unresectable or recurrent/metastatic disease
- •STEP 1: Evaluable disease as defined by RECIST v 1.1
- •STEP 1: Up to 3 prior lines of systemic therapy will be allowed in the unresectable/recurrent/metastatic setting. Treatment naïve patients will be allowed.
- •Note: Combination etoposide, doxorubicin, cisplatin, and mitotane (EDP-M) is considered 1 line of therapy. For patients who received mitotane ≤ 6 months prior to registration, mitotane should be discontinued 28 days prior to study registration AND a mitotane level must be documented to be < 2 mg/L prior to registration. Patients who have received mitotane within 6 months of enrollment and who have mitotane levels ≥ 2 mg/L will not be eligible to enroll
- •STEP 1: No prior treatment with cabozantinib or other cMET inhibitors, or anti-CTLA-4, or anti-PD-1/PD-L1 therapy
- •STEP 1: Prior external beam radiation therapy (any area radiated within a month prior to study registration cannot be used as an index lesion and only growth outside of the radiation field can be considered for disease progression), systemic cytotoxic chemotherapy, targeted therapies will be allowed, as long as not administered within 14 days before study registration, and provided any acute treatment-related associated toxicities have recovered to ≤ grade 1 except for alopecia, peripheral neuropathy or other residual toxicities that are not deemed clinically significant
- •STEP 1: Potential trial participants should have recovered from clinically significant adverse events, and wound healing is clinically adequate of their most recent therapy/intervention prior to enrollment
- •STEP 1: Age 12 years and above; and BSA ≥ 1.2m^2
- •Eastern Cooperative Oncology Group (ECOG) performance 0 - 2 (age 18 and above); or
- •Patients 12 to <16 years of age will be assessed by the Lansky scale and should have a score ≥ 50; or
- •Patients ≥ 16 to <18 years of age will be assessed by the Karnofsky scale, and should have a score ≥ 50
- •STEP 1: Absolute neutrophil count (ANC) ≥ 1,000/mcL without colony stimulating factor support within 2 weeks prior
- •Transfusion support is allowed if ≥ 7 days from obtaining required initial laboratory
- •STEP 1: Platelet count ≥ 100,000/mcL
- •Transfusion support is allowed if ≥ 7 days from obtaining required initial laboratory
- •STEP 1: Hemoglobin ≥ 8 g/dL
- •Transfusion support is allowed if ≥ 7 days from obtaining required initial laboratory
- •STEP 1: Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
- •For patients with known Gilbert's disease, bilirubin ≤ 3 mg/dL
- •STEP 1: Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/ alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) ≤ 3 x upper limit of normal (ULN)
- •STEP 1: Random Urine Creatinine Ratio (UPCR) ≤ 1 mg/mg
- •STEP 1: Calculated (Calc.) creatinine clearance ≥ 30 mL/min
- •STEP 1: Mitotane level < 2 mg/L*
- •Only applicable for patients who have received mitotane ≤ 6 months prior to registration
- •STEP 1: Must have assessment of adrenal steroid production within 3 months prior to registration as patients will be stratified based on corticosteroid production
- •Patients will be classified as corticosteroid producing if random plasma adrenocorticotropic hormone (ACTH) is < 20 pg/mL plus random serum cortisol is > 20 mcg/dL in the absence of anti-cortisol therapy. Patients already on anti-cortisol therapy will be classified as having corticosteroid producing tumors regardless of their plasma ACTH and serum cortisol levels, as these levels can be affected by anti-cortisol therapy
- •STEP 1: Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects based on animal reproduction studies. Therefore, for women of childbearing potential only, a negative urine or serum pregnancy test, per institution standard, done ≤ 14 days prior to registration is required
- •STEP 1: 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 within 28 days of registration. To be eligible for this trial, patients should be class II or better
- •STEP 1: No known history of congenital long QT syndrome
- •STEP 1: No known history of myocarditis
- •STEP 1: No myocardial infarction (MI) or unstable angina within 6 months of registration
- •STEP 1: No clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding within 6 months of registration including, but not limited to: active peptic ulcer, known endoluminal metastatic lesion(s) with history of bleeding, inflammatory bowel disease, or other gastrointestinal conditions with increased risk of perforation
- •STEP 1: No history of gastrointestinal (GI) perforation within 6 months of registration
- •STEP 1: No known tumor with invasion into the GI tract from the outside causing increased risk of perforation or bleeding within 28 days of registration
- •STEP 1: No current radiologic or clinical evidence of pancreatitis
- •STEP 1: No history of clinically significant non-healing wounds or ulcers within 28 days of registration
- •STEP 1: No uncontrolled hypertension within 14 days of registration (defined as sustained systolic blood pressure (SBP) ≥ 150 mmHg and/or diastolic blood pressure (DBP) ≥ 90 mmHg despite optimal medical management)
- •STEP 1: No known endobronchial lesions involving the main or lobar bronchi and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage. (CT with contrast is recommended to evaluate such lesions.). No hemoptysis greater than ½ teaspoon (2.5 mL) or any other signs of pulmonary hemorrhage within the 3 months prior to registration
- •STEP 1: No history of pneumonitis
- •STEP 1: No known tumor invading or encasing any major blood vessels
- •STEP 1: No history of fracture within 28 days of registration
- •STEP 1: No known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks after major surgery (e.g., removal or biopsy of brain metastasis) before registration. Eligible patients must be neurologically asymptomatic and without corticosteroid treatment at the time of the start of study treatment
- •STEP 1: Major surgery (e.g., laparoscopic nephrectomy, GI surgery, within 2 weeks before registration. Minor surgeries within 10 days before registration. Patients with clinically relevant ongoing complications from prior surgery are not eligible
- •STEP 1: Verbalizes the ability to swallow oral tablet formulation
- •STEP 1: No history of allergic reaction attributed to compounds of similar chemical or biological composition to cabozantinib
- •STEP 1: 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 will be eligible
- •STEP 1: HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration are eligible for this trial
- •STEP 1: For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
- •STEP 1: Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
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排除标准
- 未提供
研究组 & 干预措施
Arm B (cabozantinib and cemiplimab)
Patients receive cemiplimab IV over 30 minutes on day 1 and cabozantinib PO QD on days 1-21 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI and blood sample collection throughout the study.
干预措施: Computed Tomography (Procedure)
Arm B (cabozantinib and cemiplimab)
Patients receive cemiplimab IV over 30 minutes on day 1 and cabozantinib PO QD on days 1-21 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI and blood sample collection throughout the study.
干预措施: Magnetic Resonance Imaging (Procedure)
Arm B (cabozantinib and cemiplimab)
Patients receive cemiplimab IV over 30 minutes on day 1 and cabozantinib PO QD on days 1-21 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI and blood sample collection throughout the study.
干预措施: Biospecimen Collection (Procedure)
Arm A (cabozantinib)
Patients receive cabozantinib PO QD on days 1-21 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI and blood sample collection throughout the study. Upon disease progression, patients may elect to crossover to receive combination therapy on Arm B.
干预措施: Magnetic Resonance Imaging (Procedure)
Arm A (cabozantinib)
Patients receive cabozantinib PO QD on days 1-21 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI and blood sample collection throughout the study. Upon disease progression, patients may elect to crossover to receive combination therapy on Arm B.
干预措施: Cabozantinib (Drug)
Arm A (cabozantinib)
Patients receive cabozantinib PO QD on days 1-21 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI and blood sample collection throughout the study. Upon disease progression, patients may elect to crossover to receive combination therapy on Arm B.
干预措施: Computed Tomography (Procedure)
Arm B (cabozantinib and cemiplimab)
Patients receive cemiplimab IV over 30 minutes on day 1 and cabozantinib PO QD on days 1-21 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI and blood sample collection throughout the study.
干预措施: Cemiplimab (Biological)
Arm B (cabozantinib and cemiplimab)
Patients receive cemiplimab IV over 30 minutes on day 1 and cabozantinib PO QD on days 1-21 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI and blood sample collection throughout the study.
干预措施: Cabozantinib (Drug)
Arm A (cabozantinib)
Patients receive cabozantinib PO QD on days 1-21 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI and blood sample collection throughout the study. Upon disease progression, patients may elect to crossover to receive combination therapy on Arm B.
干预措施: Biospecimen Collection (Procedure)
结局指标
主要结局
Progression free survival (PFS)
时间窗: From registration to either progression or death, assessed up to 4 years post-registration
Per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1). Will be analyzed using an intention-to-treat approach. Kaplan-Meier methodology will be used to estimate the distributions for the treatment arms. The hazard ratio, median PFS, and estimated PFS rates at 5, 10 and 15 months will be estimated along with corresponding 95% confidence intervals. A one-sided log rank-test will be used to compare the PFS distributions between the two treatment arms.
Progression free survival (PFS)
时间窗: From registration to either progression or death, assessed up to 4 years post-registration
Per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1). Will be analyzed using an intention-to-treat approach. Kaplan-Meier methodology will be used to estimate the distributions for the treatment arms. The hazard ratio, median PFS, and estimated PFS rates at 5, 10 and 15 months will be estimated along with corresponding 95% confidence intervals. A one-sided log rank-test will be used to compare the PFS distributions between the two treatment arms.
次要结局
- Duration of response(From first date of the patient achieving either a complete or partial response and progression (via RECIST v 1.1), assessed up to 4 years post-registration)
- Time to progression(From registration date and progression date, assessed up to 4 years post-registration)
- Incidence of adverse events(Up to 4 years post-registration)
- Objective response rate(Up to 4 years post-registration)
- Overall survival(From registration to death, assessed up to 4 years post-registration)