Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Urinary Bladder Neoplasms

Carcinoma, Renal Cell

Carcinoma, Transitional Cell

Urologic Neoplasms

Kidney Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urologic Diseases

Male Urogenital Diseases

Adenocarcinoma

Kidney Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Transitional Cell Carcinoma

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Daratumumab

Immunoglobulins

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.

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.

Biopsy

Laboratory Biomarker Analysis

Metastasectomy

Nephrectomy

Matthew T Campbell

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.

Daratumumab in Treating Patients With Muscle Invasive Bladder Cancer or Metastatic Kidney Cancer

A Pilot Study of Daratumumab (CD38 Antagonist) in Patients With Metastatic Renal Cell Carcinoma or Muscle Invasive Bladder Cancer

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.

To be defined as a delay greater than 4 weeks from planned intervention (week 10-12).

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).

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).

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.

Janssen Research & Development, LLC

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Gland and Hormone Related Diseases

Hypogonadism

Gonadal Disorders

Endocrine System Diseases

Methyltestosterone

Testosterone

Testosterone undecanoate

Testosterone enanthate

Testosterone 17 beta-cypionate

Androgens

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Anabolic Androgenic Steroids

Anabolic Agents

Patients with low testosterone levels receive testosterone cypionate IM QW for 3 months.

Patients with normal testosterone levels receive standard peri-operative care.

Best Practice

Quality-of-Life Assessment

Ancillary studies; Quality of life questionnaires will be given both preoperatively and at 3-months postoperatively

Questionnaire Administration

Testosterone Cypionate

Kenneth Ogan, MD

Mersiha Torlak

This phase I trial investigates the safety of testosterone replacement therapy around the time of major urologic surgery (perioperative) in order to improve quality of life and post-operative outcomes such as decreased length of hospital stay, complications, and mortality in patients with low testosterone levels. Studies have demonstrated that patients undergoing testosterone replacement therapy have increased lean body mass, decreased fat mass and have improved physical function. Testosterone replacement therapy can also stimulate bone formation and may decrease the risk of fracture. Information from this trial may be used to support the incorporation of testosterone level testing and testosterone replacement into the perioperative treatment decision-making process.

PRIMARY OBJECTIVE:

I. To examine the safety and feasibility of perioperative testosterone replacement (TR) therapy in hypogonadal male patients undergoing major operations.

OUTLINE: Patients are assigned to 1 of 2 arms.

ARM I: Patients with low testosterone levels receive testosterone cypionate intramuscularly (IM) once a week (QW) for 3 months in the absence of disease progression or unacceptable toxicity.

ARM II: Patients with normal testosterone levels receive standard peri-operative care.

Perioperative Testosterone Replacement Therapy for the Improvement of Post-Operative Outcomes in Patients With Low Testosterone

Perioperative Testosterone Replacement Therapy Improves Outcomes: A Pilot Safety and Feasibility Study

The Patient Reported Outcomes Measurement Information System (PROMIS Global Health-10) is a 10 question survey that uses questions concerning physical function, overall quality of life, physical health, mood, ability to participate in social roles and activities, pain and fatigue to arrive at a score between 10 and 50. Patient's score are the outcome we will measure.

The Fried Frailty Criteria uses a comorbidity scale, measures of activity, physical tests of strength and speed, nutritional status and anatomic features to produce a score from 0-5. These numbers correspond with the following frailty categorizations: non-frail (score 0), pre-frail (score 1-2) and frail (score 3-5). This score represents one outcome measure.

Major complication considered Clavien-Dindo IIIb and above.

Minor complication considered Clavien-Dindo IIIb and below.

Admissions to the ICU between post-op day 1 to 90 days post surgery

Number of days stayed in the hospital after surgery

Determined by if patient is discharged to home, to home with services, or to facility.

Readmissions to hospital after discharge within 90 days

Levels of Testosterone determined by laboratory blood draw

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Daratumumab in Treating Patients With Muscle Invasive Bladder Cancer or Metastatic Kidney Cancer	NCT03473730	Bladder Urothel... Clear Cell Rena... Malignant Urina... Metastatic Kidn... Stage IV Renal ...	Biopsy Daratumumab Laboratory Biom... Metastasectomy Nephrectomy	18 Years -	M.D. Anderson Cancer Center
Perioperative Testosterone Replacement Therapy for the Improvement of Post-Operative Outcomes in Patients With Low Testosterone	NCT04731376	Hypogonadism Malignant Urina... Urinary System ... Urinary System ...	Best Practice Quality-of-Life... Questionnaire A... Testosterone Cy...	18 Years -	Emory University

Spots Global Cancer Trial Database for malignant urinary system neoplasm