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

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

INTRODUCTION

  • Org Study ID: 2017-0688
  • Secondary ID: NCI-2018-00800, 2017-0688, P30CA016672
  • NTC ID: NCT03473730
  • Sponsor: 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


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.


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

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Incidence of adverse events

Primary Outcome 1 - Timeframe: Up to 2 weeks after completion of study treatment (bladder cohort) or 6 weeks post-surgery (renal cohort)

Primary Outcome 2 - Measure: Rate of surgical delay (Bladder cohort)

Primary Outcome 2 - Timeframe: Up to 2 weeks after completion of study treatment

Primary Outcome 3 - Measure: Incidence of surgical complications (Bladder cohort)

Primary Outcome 3 - Timeframe: At 30 days post-surgery

CONDITION

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

ELIGIBILITY


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)

Gender: All

Minimum Age: N/A

Maximum Age: 18 Years

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Matthew T Campbell

Role: Principal Investigator

Affiliation: M.D. Anderson Cancer Center

Overall Contact

Name: Matthew T Campbell

Phone: 713-792-2830

Email: mcampbell3@mdanderson.org

LOCATION

Facility Status Contact
Facility: M D Anderson Cancer Center
Houston, Texas 77030
United States 		Status: Recruiting Contact:
Matthew T. Campbell
713-792-2830

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