Daratumumab in Patients With Metastatic Renal Cell Carcinoma (MRCC) or Muscle Invasive Bladder Cancer

• Status: Recruiting
• Trial end date: 2020-03-01
• Target enrollment: 30
• Participant gender: All

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.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: M.D. Anderson Cancer Center
• Collaborator: Janssen Research & Development, LLC
• Treatments: Antibodies, Monoclonal; Daratumumab

Criteria

Inclusion Criteria:

1. RENAL & BLADDER COHORT Consent to MD Anderson laboratory protocol PA13-0291.

2. RENAL COHORT Histological documentation of renal cell carcinoma with a clear cell component in the metastatic renal cell carcinoma cohort.

3. 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.

4. RENAL COHORT Patients must have measurable disease based on RECIST v1.1 criteria in at least one site that is not the site for planned surgical resection or serial biopsy.

5. RENAL COHORT If the kidney primary tumor is in place this is the preferred site of biopsy.

6. 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.

7. RENAL & BLADDER Subject must be >/=18 years of age.

8. 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);

9. 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.

10. RENAL & BLADDER ECOG performance status (PS) grade of

11. RENAL COHORT Recovery to baseline orto any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy;

12. RENAL COHORT Clinical laboratory values at screening: organ and marrow function and laboratory values as follows within 4 days before the first dose of daratumumab: a. The ANC >/= 1500/mm^3 without colony stimulating factor support; b. Platelets >/= 100,000/mm^3; c. Hemoglobin >/= 9 g/dL; d. Bilirubinknown Gilbert's disease, bilirubin/= 2.8 g/dl; f. Serum creatinine clearance (CrCl) >/= 20 mL/min. Dialysis patients will be excluded. For creatinine clearance estimation, the Cockcroft and Gault equation should be used: i. Male: CrCl (mL/min) = (140 - age) × wt (kg) / (serum creatinine × 72); ii. Female: Multiply above result by 0.85; g. ALT and ASTphosphorus, calcium, magnesium and potassium >/= LLN.

13. 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.

14. BLADDER Histological documentation of urothelial cancer either on outside transurethral bladder biopsy or on initial transurethral bladder biopsy at MD Anderson under PA13-0291

15. BLADDER Patients may not have evidence of metastatic disease on baseline computed tomography (CT) or magnetic imaging resonance of the chest, abdomen, or pelvis.

16. BLADDER Patients must be considered to be an operative candidate by the urology service at MD Anderson Cancer Center.

17. BLADDER The patient must be systemic treatment naïve, previous intra-vesicle therapy is allowed.

18. BLADDER Subjects must be considered cisplatin ineligible as per treating physician due to renal dysfunction, hearing impairment, or co-morbidities. Cisplatin ineligibility defined as: GFR less than 60; CHF NYHA class III or higher; Peripheral neuropathy grade 2 or higher; ECOG PS 2 or higher; impaired hearing.

19. BLADDER Clinical laboratory values at screening: a. The ANC >/= 1500/mm^3 without colony stimulating factor support; b. Platelets >/= 100,000/mm^3; c. Hemoglobin >/= 9 g/dL; d. Bilirubinbilirubin/= 2.8 g/dl; f. Serum creatinine clearance (CrCl) >/= 20 mL/min. Dialysis patients will be excluded. For creatinine clearance estimation, the Cockcroft and Gault equation should be used: i. Male: CrCl (mL/min) = (140 - age) × wt (kg) / (serum creatinine × 72); ii. Female: Multiply above result by 0.85; g. ALT and AST Exclusion Criteria:

1. RENAL & BLADDER Currently enrolled in another interventional study.

2. RENAL COHORT The subject has received any other type of investigational agent within 28 days before the first dose of study treatment;

3. 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;

4. RENAL & BLADDER Known evidence of an active infection requiring systemic therapy such as human immunodeficiency virus (HIV), active hepatitis, or fungal infection.

5. RENAL & BLADDER History of clinically significant cardiovascular disease including, but not limited to: Myocardial infarction or unstable anginatreatment initiation; Clinically significant cardiac arrhythmia; Deep vein thrombosis, pulmonary embolism, strokefailure (New York Heart Association class III-IV); Pericarditis/clinically significant pericardial effusion; Myocarditis; Endocarditis

6. 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)

7. RENAL & BLADDER Any condition that in the opinion of the investigator, would preclude participation in this study.