A Pilot Study of Daratumumab (CD38 Antagonist) in Patients with Metastatic Renal Cell Carcinoma or Muscle Invasive Bladder Cancer
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 17
- 试验地点
- 1
- 主要终点
- Incidence of adverse events
研究概览
简要总结
Objectives:
Primary:
Safety and tolerability of therapy with daratumumab in a cohort of patients with metastatic renal cell carcinoma and a cohort of patients with muscle invasive bladder cancer.
Secondary:
1A. To assess the proportion of patients who achieve pathological CR with daratumumab in patients with muscle invasive bladder cancer.
1B. To assess the objective response rate (ORR) to daratumumab in patients with metastatic renal cell carcinoma.
- To assess the progression free survival for patients with metastatic renal cell carcinoma receiving Daratumumab.
详细描述
Detailed Description:
Bladder Cancer Cohort:
Study Drug Administration:
If you are eligible and agree to take part in this study, you will receive daratumumab by vein 1 time each week for 4 weeks before your cystectomy. During Week 1, your dose of daratumumab will be given over 8 hours. After that, each dose will be given over about 4 hours.
In this study, the following will be done to lower the chance of a daratumumab infusion related reaction:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •RENAL & BLADDER COHORT: Consent to Monroe Dunaway (MD) Anderson laboratory protocol PA13-0291
- •RENAL COHORT: Histological documentation of renal cell carcinoma with a clear cell component in the metastatic renal cell carcinoma cohort
- •RENAL COHORT: Patients with an outside biopsy within 12 months is allowed for entry requirements; during the screening phase, patients without a tissue diagnosis may undergo a renal biopsy for histologic confirmation on PA13-0291
- •RENAL COHORT: Patients must have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 criteria in at least one site that is not the site for planned surgical resection or serial biopsy
- •RENAL COHORT: If the kidney primary tumor is in place this is the preferred site of biopsy
- •RENAL COHORT: Patients who have progression of disease or intolerance to a tyrosine kinase inhibitor (TKI) and to a PD-1 (like nivolumab) or PD-L1 (like atezolizumab) regimen; there is no limit to number of prior treatment regimens as long as the patient meets other eligibility criteria
- •RENAL & BLADDER: Sexually active subjects (men and women) must agree to use medically accepted barrier methods of contraception (eg, male or female condom) during the course of the study and for 4 months after the last dose of study drug(s), even if oral contraceptives are also used; all subjects of reproductive potential must agree to use both a barrier method and a second method of birth control during the course of the study and for 4 months after the last dose of study drug(s)
- •RENAL & BLADDER: Female subjects of childbearing potential must not be pregnant at screening; females of childbearing potential are defined as premenopausal females capable of becoming pregnant (ie, females who have had any evidence of menses in the past 12 months, with the exception of those who had prior hysterectomy); however, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, low body weight, ovarian suppression or other reasons
- •RENAL & BLADDER: Eastern Cooperative Oncology Group (ECOG) performance status (PS) grade of =< 2
- •RENAL COHORT: Recovery to baseline or =< grade 1 Common Terminology Criteria for Adverse Events (CTCAE) v.5.0 from toxicities related to any prior treatments, unless adverse events (AEs) are clinically nonsignificant and/or stable on supportive therapy
- •RENAL COHORT: Absolute neutrophil count (ANC) >= 1500/mm^3 without colony stimulating factor support (within 4 days before the first dose of daratumumab)
- •RENAL COHORT: Platelets >= 100,000/mm^3 (within 4 days before the first dose of daratumumab)
- •RENAL COHORT: Hemoglobin >= 9 g/dL (within 4 days before the first dose of daratumumab)
- •RENAL COHORT: Bilirubin =< 1.5 x upper limit of normal (ULN); for subjects with known Gilbert's disease, bilirubin =< 3.0 mg/dL (within 4 days before the first dose of daratumumab)
- •RENAL COHORT: Serum albumin >= 2.8 g/dl (within 4 days before the first dose of daratumumab)
- •RENAL COHORT: Serum creatinine clearance (CrCl) >= 20 mL/min (within 4 days before the first dose of daratumumab); dialysis patients will be excluded; for creatinine clearance estimation, the Cockcroft and Gault equation should be used
- •RENAL COHORT: Serum phosphorus >= lower limit of normal (LLN) (within 4 days before the first dose of daratumumab)
- •RENAL COHORT: Calcium >= LLN (within 4 days before the first dose of daratumumab)
- •RENAL COHORT: Magnesium >= LLN (within 4 days before the first dose of daratumumab)
- •RENAL COHORT: Potassium >= LLN (within 4 days before the first dose of daratumumab)
- •RENAL & BLADDER: Each subject must sign an informed consent form (ICF) indicating that he understands the purpose of and procedures required for the study and is willing to participate in the study
- •BLADDER: Histological documentation of urothelial cancer either on outside transurethral bladder biopsy or on initial transurethral bladder biopsy at MD Anderson under PA13-0291
- •BLADDER: Patients may not have evidence of metastatic disease on baseline computed tomography (CT) or magnetic imaging resonance of the chest, abdomen, or pelvis
- •BLADDER: Patients must be considered to be an operative candidate by the urology service at MD Anderson Cancer Center
- •BLADDER: The patient must be systemic treatment naive, previous intra-vesicle therapy is allowed
- •BLADDER: Subjects must be considered cisplatin ineligible as per treating physician due to renal dysfunction, hearing impairment, or co-morbidities; cisplatin ineligibility defined as: glomerular filtration rate (GFR) less than 60; congestive heart failure (CHF) New York Heart Association (NYHA) class III or higher; peripheral neuropathy grade 2 or higher; ECOG PS 2 or higher; impaired hearing
- •BLADDER: ANC >= 1500/mm^3 without colony stimulating factor support (clinical laboratory values at screening)
- •BLADDER: Platelets >= 100,000/mm^3 (clinical laboratory values at screening)
- •BLADDER: Hemoglobin >= 9 g/dL (clinical laboratory values at screening)
- •BLADDER: Bilirubin =< 1.5 x the ULN; for subjects with known Gilbert's disease, bilirubin =< 3.0 mg/dL (clinical laboratory values at screening)
- •BLADDER: Serum albumin >= 2.8g/dl (clinical laboratory values at screening)
- •BLADDER: Serum creatinine clearance (CrCl) >= 20 mL/min (clinical laboratory values at screening); dialysis patients will be excluded; for creatinine clearance estimation, the Cockcroft and Gault equation should be used
- •BLADDER: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3.0 x ULN (clinical laboratory values at screening)
- •BLADDER: Each subject must sign an informed consent form (ICF) indicating that he understands the purpose of and procedures required for the study and is willing to participate in the study
排除标准
- •RENAL & BLADDER: Currently enrolled in another interventional study
- •RENAL COHORT: The subject has received any other type of investigational agent within 28 days before the first dose of study treatment
- •RENAL COHORT: Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 2 weeks before the first dose of study treatment; eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of the start of study treatment
- •RENAL & BLADDER: Known evidence of an active infection requiring systemic therapy such as human immunodeficiency virus (HIV), active hepatitis, or fungal infection
- •RENAL & BLADDER: History of clinically significant cardiovascular disease including, but not limited to:
- •Myocardial infarction or unstable angina =< 6 months prior to treatment initiation
- •Clinically significant cardiac arrhythmia
- •Deep vein thrombosis, pulmonary embolism, stroke =< 6 months prior to treatment initiation
- •Congestive heart failure (New York Heart Association class III-IV)
- •Pericarditis/clinically significant pericardial effusion
- •Myocarditis
- •Endocarditis
- •RENAL & BLADDER: Other prior malignancy (exceptions: adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or any other cancer in situ currently in complete remission) =< 2 years prior to enrollment
- •RENAL & BLADDER: Any condition that in the opinion of the investigator, would preclude participation in this study
- •RENAL & BLADDER: Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]); subjects with resolved infection (ie, subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen [antiHBc] and/or antibodies to hepatitis B surface antigen [antiHBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels; those who are PCR positive will be excluded; EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (antiHBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR; seropositive for hepatitis C (except in the setting of a sustained virologic response [SVR], defined as aviremia at least 12 weeks after completion of antiviral therapy)
研究组 & 干预措施
Cohort 1 Renal (daratumumab, biopsy, surgery)
Patients receive daratumumab IV over 8 hours for the first dose and then over 4 hours for all doses thereafter during weeks 1-8. Treatment repeats every week for up to 8 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo biopsy, nephrectomy, or metastasectomy during weeks 10-12. Patients may then restart treatment with daratumumab beginning 2 weeks after biopsy or 4-6 weeks after nephrectomy or metastasectomy. Cycles repeat every 2 weeks for 4 months and then monthly for 1 year in the absence of disease progression or unacceptable toxicity.
干预措施: Biopsy (Procedure)
Cohort 1 Renal (daratumumab, biopsy, surgery)
Patients receive daratumumab IV over 8 hours for the first dose and then over 4 hours for all doses thereafter during weeks 1-8. Treatment repeats every week for up to 8 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo biopsy, nephrectomy, or metastasectomy during weeks 10-12. Patients may then restart treatment with daratumumab beginning 2 weeks after biopsy or 4-6 weeks after nephrectomy or metastasectomy. Cycles repeat every 2 weeks for 4 months and then monthly for 1 year in the absence of disease progression or unacceptable toxicity.
干预措施: Daratumumab (Biological)
Cohort 1 Renal (daratumumab, biopsy, surgery)
Patients receive daratumumab IV over 8 hours for the first dose and then over 4 hours for all doses thereafter during weeks 1-8. Treatment repeats every week for up to 8 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo biopsy, nephrectomy, or metastasectomy during weeks 10-12. Patients may then restart treatment with daratumumab beginning 2 weeks after biopsy or 4-6 weeks after nephrectomy or metastasectomy. Cycles repeat every 2 weeks for 4 months and then monthly for 1 year in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Cohort 1 Renal (daratumumab, biopsy, surgery)
Patients receive daratumumab IV over 8 hours for the first dose and then over 4 hours for all doses thereafter during weeks 1-8. Treatment repeats every week for up to 8 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo biopsy, nephrectomy, or metastasectomy during weeks 10-12. Patients may then restart treatment with daratumumab beginning 2 weeks after biopsy or 4-6 weeks after nephrectomy or metastasectomy. Cycles repeat every 2 weeks for 4 months and then monthly for 1 year in the absence of disease progression or unacceptable toxicity.
干预措施: Metastasectomy (Procedure)
Cohort 1 Renal (daratumumab, biopsy, surgery)
Patients receive daratumumab IV over 8 hours for the first dose and then over 4 hours for all doses thereafter during weeks 1-8. Treatment repeats every week for up to 8 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo biopsy, nephrectomy, or metastasectomy during weeks 10-12. Patients may then restart treatment with daratumumab beginning 2 weeks after biopsy or 4-6 weeks after nephrectomy or metastasectomy. Cycles repeat every 2 weeks for 4 months and then monthly for 1 year in the absence of disease progression or unacceptable toxicity.
干预措施: Nephrectomy (Procedure)
Cohort 2 Bladder (daratumumab)
Patients receive daratumumab IV over 8 hours for the first dose and then over 4 hours for all doses thereafter beginning at week 1. Cycles repeat every week for up to 4 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Daratumumab (Biological)
Cohort 2 Bladder (daratumumab)
Patients receive daratumumab IV over 8 hours for the first dose and then over 4 hours for all doses thereafter beginning at week 1. Cycles repeat every week for up to 4 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
结局指标
主要结局
Incidence of adverse events
时间窗: Up to 2 weeks after completion of study treatment (bladder cohort) or 6 weeks post-surgery (renal cohort)
Adverse events will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Will be recorded for all patients, recording name, grade, start and end dates, attribution to study drug, and whether the event was alleviated or controlled with relevant appropriate care similar to Phase I trials. Adverse events, serious adverse events (SAEs), and toxicities (TOX) will be summarized by grade and attribution in descriptive tables and figures by cohort.
Incidence of surgical complications (Bladder cohort)
时间窗: At 30 days post-surgery
Rate of surgical delay (Bladder cohort)
时间窗: Up to 2 weeks after completion of study treatment
To be defined as a delay greater than 4 weeks from planned intervention (week 10-12).
次要结局
- Pathologic response (Bladder cohort)(Up to 2 weeks after completion of study treatment)
- Best objective response rate (ORR) (Renal cohort)(Up to 2 weeks after completion of study treatment)
- Progression-free survival (PFS) (Renal cohort)(From the start of study treatment up to 6 weeks post-surgery)