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

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


  • Org Study ID: 2017-0688
  • Secondary ID: NCI-2018-00800
  • NCT ID: NCT03473730
  • NCT Alias:
  • Sponsor: M.D. Anderson Cancer Center - Other
  • Source: 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.

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.

Overal Status Start Date Phase Study Type
Recruiting May 29, 2018 Early Phase 1 Interventional

Primary Outcomes:

Primary Outcome 1 - Measure: Adverse Events of Daratumumab Determined by CTCAE v4.03

Primary Outcome 1 - Time Frame: Start of study drug up to 90 days after drug discontinued

Primary Outcome 2 - Measure: Rate of Surgical Delay in Bladder Cohort Defined as Delay Greater than 4 weeks from Planned Intervention

Primary Outcome 2 - Time Frame: 4 weeks

Condition:

  • Malignant Neoplasms of Urinary Tract

Eligibility

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 or to 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. Bilirubin known 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 AST phosphorus, 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. Bilirubin 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 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 angina treatment initiation; Clinically significant cardiac arrhythmia; Deep vein thrombosis,
pulmonary embolism, stroke failure (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.
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Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Official Information

Name: Matthew Campbell, MD

Role: Principal Investigator

Affiliation: M.D. Anderson Cancer Center

Overall Contact

Name: Matthew Campbell, MD

Phone: 713-792-2830

Email: mcampbell3@mdanderson.org

Link: University of Texas MD Anderson Cancer Center Website

Location

Facility Status Contact
University of Texas MD Anderson Cancer Center
Houston, Texas 77030
United States
Recruiting

mcampbell3@mdanderson.org