Atezolizumab Plus Etoposide and Platinum in Small Cell Bladder Cancer

  • STATUS
    Recruiting
  • End date
    Jun 11, 2026
  • participants needed
    63
  • sponsor
    Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Updated on 11 July 2022
carcinoma
carboplatin
atezolizumab
bladder tumor

Summary

This is a single arm, Phase II trial involving the use of atezolizumab plus platinum and etoposide for patients with locally advanced urothelial cancer. The primary goal of this trial is to assess the pathologic complete response rate at cystectomy in patients after being treated with a combination therapy of atezolizumab, platinum, and etoposide.

Description

The study population will include male and female patients over the age of 18 with invasive (cT1-cT4) small cell / neuroendocrine carcinoma of the bladder (MIBC), with or without urothelial cancer component, who are eligible for platinum based chemotherapy and immunotherapy. All patients will be fit to undergo surgical resection of their cancer by cystectomy. Patients with resectable N1 disease within the true pelvis are eligible.

Participants will receive:

Atezolizumab 1,200 mg IV Day 1 Etoposide 100 mg/m2 IV on Days 1-3 Carboplatin AUC 5 IV on Day 1 or Cisplatin 70 mg/m2 IV on Day 1 (Patients can be switched at investigator's discretion between cisplatin and carboplatin between cycles. Rationale must be provided.) Repeat q 21 days x 4 cycles

Atezolizumab will be administered by intravenous (IV) infusion at a fixed dose of 1200 mg Day 1 of every 21 day cycle with chemotherapy x 4 cycles. Following cystectomy, Atezolizumab maintenance Q 21 days will continue until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status (e.g., symptomatic deterioration such as pain secondary to disease), or up to 1 year (e.g., 16 cycles).

Details
Condition Small Cell Neuroendocrine Carcinoma of Bladder, Bladder Cancer, Urothelial Carcinoma Bladder
Treatment cisplatin, etoposide, carboplatin, Atezolizumab, Cystectomy
Clinical Study IdentifierNCT05312671
SponsorSidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Last Modified on11 July 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Histologically confirmed invasive carcinoma of the bladder with pure, or any component of, small cell or high grade neuroendocrine features with or without urothelial cancer
localized ≥ cT1-T4aN1
A formalin-fixed paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or
at least 15 slides containing unstained, freshly cut, serial sections should be submitted
along with an associated pathology report prior to study enrollment. If less than 15 slides
are available, the patient may still be eligible for the study, after Principal
Investigator confirmation has been obtained
If archival tumor tissue is unavailable or is determined to be unsuitable for required
testing, tumor tissue must be obtained from a biopsy performed at screening
Medically fit to undergo chemotherapy, immunotherapy and cystectomy
years old at time of consent
ECOG performance status of 0 or 1
Adequate hematologic and end organ function, defined by the following laboratory
results obtained within 14 days prior to randomization
ANC ≥ 1500 cells/μL without granulocyte colony-stimulating factor support
Lymphocyte count ≥ 500/μL
Platelet count ≥ 100,000/μL without transfusion
Hemoglobin ≥ 9.0 g/dL -patients may be transfused to meet this criterion
INR or aPTT ≤ 1.5 × upper limit of normal (ULN) This applies only to patients who are
not receiving therapeutic anticoagulation; patients receiving therapeutic
anticoagulation should be on a stable dose
AST, ALT, and alkaline phosphatase ≤ 2.5 × ULN
Serum bilirubin ≤ 1.5 × ULN Patients with known Gilbert disease who have serum
bilirubin level ≤3 × ULN may be enrolled
Serum albumin >= 25 g/L (2.5 g/dL)
Negative HIV test at screening (with the following exception: patients with a positive
HIV test at screening are eligible provided they are stable on anti-retroviral
therapy, have a CD4 count >= 200/µL, and have an undetectable viral load)
Negative hepatitis B surface antigen (HBsAg) test at screening
Negative total hepatitis B core antibody (HBcAb) test at screening, or positive total
HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening The
HBV DNA test will be performed only for patients who have a negative HBsAg test and a
positive total HBcAb test
Creatinine clearance >30. Patients receiving cisplatin must have creatinine clearance
>50
For women of childbearing potential (WOCBP): agreement to remain abstinent (refrain
from heterosexual intercourse) or use contraceptive methods, and agreement to refrain
from donating eggs, as defined below
Women must remain abstinent or use contraceptive methods with a failure rate of <1%
per year during the treatment period and for 5 months after the final dose of
atezolizumab and for 30 days after the final dose of cisplatin/ carboplatin and
etoposide. Women must refrain from donating eggs during this same period
A woman is considered to be of childbearing potential if she is postmenarchal, has not
reached a postmenopausal state (>= 12 continuous months of amenorrhea with no
identified cause other than menopause), and has not undergone surgical sterilization
(removal of ovaries and/or uterus). The definition of childbearing potential may be
adapted for alignment with local guidelines or requirements
Examples of contraceptive methods with a failure rate of < 1% per year include
bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit
ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices
The reliability of sexual abstinence should be evaluated in relation to the duration of the
clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence
(e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not
adequate methods of contraception
For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use
contraceptive measures, and agreement to refrain from donating sperm, as defined
below
With a female partner of childbearing potential who is not pregnant, or a pregnant
female partner men who are not surgically sterile must remain abstinent or use a
condom plus an additional contraceptive method that together result in a failure rate
of < 1% per year during the treatment period and for 8 months after the final dose of
atezolizumab and 120 days after the final dose of etoposide. Men must refrain from
donating sperm during this same period
The reliability of sexual abstinence should be evaluated in relation to the duration
of the clinical trial and the preferred and usual lifestyle of the patient. Periodic
abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and
withdrawal are not adequate methods of contraception
Patients who give a written informed consent obtained according to local guidelines
Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for
chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids
for orthostatic hypotension or adrenal insufficiency are eligible for the study

Exclusion Criteria

No prior systemic treatment for small-cell bladder cancer (SCBC)
Patients with concurrent upper urinary tract (i.e. ureter, renal pelvis) invasive
urothelial carcinoma. (NOTE: Patients with history of non-invasive (Ta, Tis) upper
tract urothelial carcinoma that has been definitively treated with at least one post-
treatment disease assessment (i.e. cytology, biopsy, imaging) that demonstrates no
evidence of residual disease are eligible). Individual cases will be discussed at
investigator discretion
Patients with another active second malignancy other than non-melanoma skin cancers
and biochemical relapsed prostate cancer. Patients that have completed all necessary
therapy and are considered to be at less than 30% risk of relapse are not considered
to have an active second malignancy and are eligible for enrollment
Patients who have received prior systemic chemotherapy for urothelial bladder cancer
Prior BCG and intravesical chemotherapy are allowed
Any metastatic disease including leptomeningeal disease or brain metastasis on
baseline brain imaging
Uncontrolled tumor-related pain - Patients requiring pain medication must be on a
stable regimen at study entry
Patients requiring pain medication must be on a stable regimen at study entry
Uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium > 12 mg/dL
or corrected serum calcium > ULN
Active or history of autoimmune disease or immune deficiency, including, but not
limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus
erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid
antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome
or multiple sclerosis, with the following exceptions
Patients with a history of autoimmune-related hypothyroidism who are on thyroid-
replacement hormone are eligible for the study
Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are
eligible for the study
Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with
dermatologic manifestations only (e.g., patients with psoriatic arthritis are
excluded) are eligible for the study provided all of following conditions are met
Rash must cover < 10% of body surface area
Disease is well controlled at baseline and requires only low-potency topical
corticosteroids
No occurrence of acute exacerbations of the underlying condition requiring psoralen
plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral
calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12
months
Individual cases can be discussed at investigator discretion. Refer to Appendix H for
more details
History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis
obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of
active pneumonitis on screening chest computed tomography (CT) scan. History of
radiation pneumonitis in the radiation field (fibrosis) is permitted
Active tuberculosis
Significant cardiovascular disease (such as New York Heart Association Class II or
greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3
months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
Patients who have undergone major surgery (e.g. intra-thoracic, intra- abdominal or
intra-pelvic), open biopsy or significant traumatic injury ≤ 4 weeks prior to starting
study drug, or patients who have had minor procedures (i.e. TURBT), percutaneous
biopsies or placement of vascular access device ≤1 week prior to starting study drug
or who have not recovered from side effects of such procedure or injury
History of malignancy other than small cell bladder cancer within 5 years prior to
screening, with the exception of malignancies with a negligible risk of metastasis or
death (e.g., 5-year OS rate > 90%), such as adequately treated carcinoma in situ of
the cervix, non melanoma skin carcinoma, localized prostate cancer, ductal carcinoma
in situ, or Stage I uterine cancer
Severe infection within 4 weeks prior to initiation of study treatment, including, but
not limited to, hospitalization for complications of infection, bacteremia, or severe
pneumonia
Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation
of study treatment. Patients receiving prophylactic antibiotics (e.g., to prevent a
urinary tract infection or chronic obstructive pulmonary disease exacerbation) are
eligible for the study
Prior allogeneic stem cell or solid organ transplantation
Any other disease, metabolic dysfunction, physical examination finding, or clinical
laboratory finding that contraindicates the use of an investigational drug, may affect
the interpretation of the results, or may render the patient at high risk from
treatment complications
Treatment with a live, attenuated vaccine (e.g., FluMist®) within 4 weeks prior to
initiation of study treatment, or anticipation of need for such a vaccine during
atezolizumab treatment or within 5 months after the final dose of Atezolizumab
Current treatment with anti-viral therapy for HBV
Treatment with investigational therapy within 28 days prior to initiation of study
treatment
Prior treatment with CD137 agonists or other immune checkpoint blockade therapies
including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
Treatment with systemic immunostimulatory agents (including, but not limited to
interferon and interleukin 2 [IL-2]) within 4 weeks or 5 half-lives of the drug
(whichever is longer) prior to initiation of study treatment
Treatment with systemic immunosuppressive medication (including, but not limited to
corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-
TNF-α agents) within 2 weeks prior to initiation of study treatment, or anticipation
of need for systemic immunosuppressive medication during study treatment
Patients who received acute, low-dose systemic immunosuppressant medication or a
one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of
corticosteroids for a contrast allergy) are eligible for the study after Principal
Investigator confirmation has been obtained
History of severe allergic anaphylactic reactions to chimeric or humanized antibodies
or fusion proteins
Known hypersensitivity to Chinese hamster ovary cell products or to any component of
the atezolizumab formulation
Known allergy or hypersensitivity to any component of Cisplatin, carboplatin or
etoposide
Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment
or within 5 months of atezolizumab after the final dose of study treatment. Women of
childbearing potential must have a negative serum pregnancy test result within 14 days
prior to initiation of study treatment
Patients who have had radiotherapy to the bladder, or radiotherapy ≤ 4 weeks prior to
starting study drug, or who have not recovered from radiotherapy toxicities
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer  to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note