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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03473730
Recruitment Status : Active, not recruiting
First Posted : March 22, 2018
Last Update Posted : September 26, 2022
Sponsor:
Collaborators:
Janssen Research & Development, LLC
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Bladder Urothelial Carcinoma Clear Cell Renal Cell Carcinoma Malignant Urinary System Neoplasm Metastatic Kidney Carcinoma Stage IV Renal Cell Cancer AJCC v8 Procedure: Biopsy Biological: Daratumumab Other: Laboratory Biomarker Analysis Procedure: Metastasectomy Procedure: Nephrectomy Early Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 17 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study of Daratumumab (CD38 Antagonist) in Patients With Metastatic Renal Cell Carcinoma or Muscle Invasive Bladder Cancer
Actual Study Start Date : May 29, 2018
Estimated Primary Completion Date : June 30, 2023
Estimated Study Completion Date : June 30, 2023


Arm Intervention/treatment
Experimental: 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.
Procedure: Biopsy
Undergo biopsy
Other Name: Bx

Biological: Daratumumab
Given IV
Other Names:
  • Anti-CD38 Monoclonal Antibody
  • Darzalex
  • HuMax-CD38
  • JNJ-54767414

Other: Laboratory Biomarker Analysis
Correlative studies

Procedure: Metastasectomy
Undergo metastasectomy

Procedure: Nephrectomy
Undergo nephrectomy

Experimental: 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.
Biological: Daratumumab
Given IV
Other Names:
  • Anti-CD38 Monoclonal Antibody
  • Darzalex
  • HuMax-CD38
  • JNJ-54767414

Other: Laboratory Biomarker Analysis
Correlative studies




Primary Outcome Measures :
  1. Incidence of adverse events [ Time Frame: 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.

  2. Rate of surgical delay (Bladder cohort) [ Time Frame: 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).

  3. Incidence of surgical complications (Bladder cohort) [ Time Frame: At 30 days post-surgery ]

Secondary Outcome Measures :
  1. Pathologic response (Bladder cohort) [ Time Frame: Up to 2 weeks after completion of study treatment ]
    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).

  2. Best objective response rate (ORR) (Renal cohort) [ Time Frame: Up to 2 weeks after completion of study treatment ]
    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).

  3. Progression-free survival (PFS) (Renal cohort) [ Time Frame: From the start of study treatment up to 6 weeks post-surgery ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03473730


Locations
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United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Janssen Research & Development, LLC
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Matthew T Campbell M.D. Anderson Cancer Center
Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03473730    
Other Study ID Numbers: 2017-0688
NCI-2018-00800 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2017-0688 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: March 22, 2018    Key Record Dates
Last Update Posted: September 26, 2022
Last Verified: September 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Urinary Bladder Neoplasms
Carcinoma, Renal Cell
Kidney Neoplasms
Urologic Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
Adenocarcinoma
Kidney Diseases
Daratumumab
Antineoplastic Agents