Clinical Trials /

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

NCT03473730

Description:

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.

Related Conditions:
  • Bladder Carcinoma
  • Clear Cell Renal Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Daratumumab in Treating Patients With Muscle Invasive Bladder Cancer or Metastatic Kidney Cancer
  • Official Title: A Pilot Study of Daratumumab (CD38 Antagonist) in Patients With Metastatic Renal Cell Carcinoma or Muscle Invasive Bladder Cancer

Clinical Trial IDs

  • ORG STUDY ID: 2017-0688
  • SECONDARY ID: NCI-2018-00800
  • SECONDARY ID: 2017-0688
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT03473730

Conditions

  • Bladder Urothelial Carcinoma
  • Clear Cell Renal Cell Carcinoma
  • Malignant Urinary System Neoplasm
  • Metastatic Kidney Carcinoma
  • Stage IV Renal Cell Cancer AJCC v8

Interventions

DrugSynonymsArms
DaratumumabAnti-CD38 Monoclonal Antibody, Darzalex, HuMax-CD38, JNJ-54767414Cohort 1 Renal (daratumumab, biopsy, surgery)

Purpose

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

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort 1 Renal (daratumumab, biopsy, surgery)ExperimentalPatients 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.
  • Daratumumab
Cohort 2 Bladder (daratumumab)ExperimentalPatients 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.
  • Daratumumab

Eligibility Criteria

        Inclusion Criteria:

          -  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

        Exclusion Criteria:

          -  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)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events
Time Frame:Up to 2 weeks after completion of study treatment (bladder cohort) or 6 weeks post-surgery (renal cohort)
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Pathologic response (Bladder cohort)
Time Frame:Up to 2 weeks after completion of study treatment
Safety Issue:
Description: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).
Measure:Best objective response rate (ORR) (Renal cohort)
Time Frame:Up to 2 weeks after completion of study treatment
Safety Issue:
Description: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).
Measure:Progression-free survival (PFS) (Renal cohort)
Time Frame:From the start of study treatment up to 6 weeks post-surgery
Safety Issue:
Description: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.

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

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