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

NCT03473730 | Completed Early Phase 1 FDA Drug

• 3 other identifiers: 2017-0688NCI-2018-00800P30CA016672
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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.

Conditions

Bladder Urothelial Carcinoma; Clear Cell Renal Cell Carcinoma; Malignant Urinary System Neoplasm; Metastatic Kidney Carcinoma; Stage IV Renal Cell Cancer AJCC V8

Outcome Measures

Primary Outcomes (3)

• 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.

  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).

  Up to 2 weeks after completion of study treatment

• Incidence of surgical complications (Bladder cohort)

  At 30 days post-surgery

Secondary Outcomes (3)

• 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

Study Arms (2)

Cohort 1 Renal (daratumumab, biopsy, surgery)

EXPERIMENTAL

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; Biological: Daratumumab; Other: Laboratory Biomarker Analysis; Procedure: Metastasectomy; Procedure: Nephrectomy

Cohort 2 Bladder (daratumumab)

EXPERIMENTAL

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; Other: Laboratory Biomarker Analysis

Interventions

Biopsy PROCEDURE

Undergo biopsy

Also known as: Bx

Cohort 1 Renal (daratumumab, biopsy, surgery)

Daratumumab BIOLOGICAL

Given IV

Also known as: Anti-CD38 Monoclonal Antibody, Darzalex, HuMax-CD38, JNJ-54767414

Cohort 1 Renal (daratumumab, biopsy, surgery); Cohort 2 Bladder (daratumumab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Cohort 1 Renal (daratumumab, biopsy, surgery); Cohort 2 Bladder (daratumumab)

Metastasectomy PROCEDURE

Undergo metastasectomy

Cohort 1 Renal (daratumumab, biopsy, surgery)

Nephrectomy PROCEDURE

Undergo nephrectomy

Cohort 1 Renal (daratumumab, biopsy, surgery)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Janssen Research & Development, LLC: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Carcinoma, Renal Cell; Urologic Neoplasms

Interventions

Biopsy; daratumumab; Metastasectomy; Nephrectomy

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Urologic Surgical Procedures; Urogenital Surgical Procedures

Study Officials

• Matthew T Campbell

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2018
• First Posted: March 22, 2018
• Study Start: May 29, 2018
• Primary Completion: January 27, 2025
• Study Completion: January 27, 2025
• Last Updated: January 30, 2025

Record last verified: 2025-01

Locations

US (1)