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. 2\. To assess the progression free survival for patients with metastatic renal cell carcinoma receiving Daratumumab.
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: You will get drugs, including steroids, acetaminophen, and/or antihistamine before the infusion. If you are considered high risk, you may also get drugs, including inhaled steroids, after the infusion. The infusion may be slowed down or stopped if you have a reaction. You may stay overnight in the hospital after the infusion so the study staff can check your health. You may ask the study staff for more information about the types of medications you will receive to lower your chance of an infusion-related reaction, including how they are administered and their risks. Length of Study: You may receive up to 4 doses of daratumumab before your surgery. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions. Your participation on the study will be over after the follow-up visit (described below). Study Visits: During Weeks 1-4: You will have a physical exam. Blood (about 2 tablespoons) will be drawn for routine and blood type testing. Daratumumab will interfere with blood type testing which is needed before blood transfusions can be given. For this reason, a test to find out your blood type will be performed before you receive daratumumab. You should carry the blood type card with you while you are on this study. During Weeks 6-8 (the week of your surgery): You will have a physical exam. Blood (about 2 tablespoons) will be drawn for routine tests and part of this sample will also be used for blood type testing. You will have surgery to remove your bladder. You will sign a separate consent form explaining the procedure and its risks in more detail. End-of-Study Visit: During Weeks 12-14, blood (about 2 tablespoons) will be drawn for routine tests. Follow-Up Visit: During Week 18, blood (about 2 tablespoons) will be drawn for routine tests and you will be asked about any side effects you are having. Renal 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 8 weeks before your nephrectomy, metastasectomy, or biopsy. 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: You will get drugs, including steroids, acetaminophen, and/or antihistamine before the infusion. If you are considered high risk, you may also get drugs, including inhaled steroids, after the infusion. The infusion may be slowed down or stopped if you have a reaction. You may stay overnight in the hospital after the infusion so the study staff can check your health. You may ask the study staff for more information about the types of medications you will receive to lower your chance of an infusion-related reaction, including how they are administered and their risks. Length of Study: You may receive up to 8 doses of daratumumab prior to your surgery or biopsy. You may receive additional doses of daratumumab after the surgery/biopsy for up to one year after your first dose. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions. Your participation on the study will be over after the follow-up visit (described below). Study Visits: During Weeks 1-8: You will have a physical exam each week before you receive daratumumab. Blood (about 2 tablespoons) will be drawn for routine and blood type testing. Daratumumab treatment will interfere with blood type testing which is needed before blood transfusions can be given. For this reason, a test to find out your blood type will be performed before you receive daratumumab. You should carry the blood type card with you while you are on this study. During Weeks 10-12 (the week of your surgery/tissue collection): You will have a physical exam. Blood (about 2 tablespoons) will be drawn for routine tests, part of this sample will also be used for blood type testing. You will have surgery to remove your kidney, a kidney cancer lesion, or repeat biopsy. You will sign a separate consent form explaining the procedure and its risks in more detail. During Weeks 14-30: You will have a physical exam and return every 2 weeks to receive daratumumab. Blood (about 2 tablespoons) will be drawn for routine and blood type testing. During Weeks 30-52: You will have a physical exam and return every month to receive daratumumab. Blood (about 2 tablespoons) will be drawn for routine and blood type testing. End-of-Study Visit: During Week 52, blood (about 2 tablespoons) will be drawn for routine tests. Follow-Up Visit: During Week 65, blood (about 2 tablespoons) will be drawn for routine tests and you will be asked about any side effects you are having.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
17
Undergo biopsy
Given IV
Correlative studies
Undergo metastasectomy
Undergo nephrectomy
M D Anderson Cancer Center
Houston, Texas, United States
Incidence of adverse events
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.
Time frame: Up to 2 weeks after completion of study treatment (bladder cohort) or 6 weeks post-surgery (renal cohort)
Rate of surgical delay (Bladder cohort)
To be defined as a delay greater than 4 weeks from planned intervention (week 10-12).
Time frame: Up to 2 weeks after completion of study treatment
Incidence of surgical complications (Bladder cohort)
Time frame: At 30 days post-surgery
Pathologic response (Bladder cohort)
Pathologic complete response (CR) (pCR) is defined as the absence of residual tumor in the radical cystectomy specimen and pelvic lymph node dissection (ie, ypT0N0). Patients who do not undergo surgery for any reason will be counted as not having a pCR. pCR rates and their 90% credible confidence intervals will be estimated using an uninformative beta distribution with a prior Beta (1,1).
Time frame: Up to 2 weeks after completion of study treatment
Best objective response rate (ORR) (Renal cohort)
ORR will be defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. Patients who have CR or partial response (PR) will be counted as having an objective response. ORR rates and their 90% credible confidence intervals will be estimated using an uninformative beta distribution with a prior Beta (1,1).
Time frame: Up to 2 weeks after completion of study treatment
Progression-free survival (PFS) (Renal cohort)
PFS will be defined as the time from first treatment to progression or death, regardless of cause, whichever comes first. Patients who are alive and free of progression at the time of data lock will be censored on the date they were last assessed for disease status (last follow-up). Patients who start a new therapy without progression will be censored on their last follow-up before starting the subsequent therapy. PFS will be estimated by Kaplan-Meier estimates.
Time frame: From the start of study treatment up to 6 weeks post-surgery
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