Atezolizumab Plus Etoposide and Platinum in Small Cell Bladder Cancer

NCT05312671 | Recruiting Phase 2 FDA Drug

• 3 other identifiers: J2208IRB00313218ML42154
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Small Cell Neuroendocrine Carcinoma of Bladder; Bladder Cancer; Urothelial Carcinoma Bladder

Keywords

Small Cell Bladder Cancer; Atezolizumab; Cisplatin; Carboplatin; Platinum; Etoposide; Cystectomy

Outcome Measures

Primary Outcomes (1)

• Pathologic complete response (ypCR) at cystectomy

  The number of participants with pathological complete responses (ypCR) at cystectomy. Pathologic complete response is defined as post-treatment cystectomy tumor stages N0 and M0, with T-stage T0.

  up to 18 months

Secondary Outcomes (7)

• Number of participants with non-muscle invasive disease

  up to 18 months

• Safety and tolerability of combination chemotherapy and cystectomy as assessed by number of participants experiencing adverse events

  4.5 years

• Incidence of brain metastases in follow-up

  up to 5 years

• 1-year overall survival rate (1-yr OS)

  up to 4 years

• 2-year overall survival rate (2-yr OS)

  up to 5 years

Study Arms (1)

Atezolizumab with Platinum and Etoposide, followed by cystectomy.

EXPERIMENTAL

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. 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).

Drug: Atezolizumab; Drug: Carboplatin; Drug: Cisplatin; Drug: Etoposide; Procedure: Cystectomy

Interventions

Atezolizumab DRUG

Atezolizumab 20 mL (1200 mg) on Day 1, once every 3 weeks for up to 20 cycles (each cycle = 21 days)

Also known as: Tecentriq

Atezolizumab with Platinum and Etoposide, followed by cystectomy.

Carboplatin DRUG

Carboplatin AUC 5 IV on Day 1, once every 3 weeks for first 4 cycles (each cycle = 21 days).

Also known as: CBDCA, Paraplatin, JM-8, NSC-241240

Atezolizumab with Platinum and Etoposide, followed by cystectomy.

Cisplatin DRUG

Cisplatin 70 mg/m2 IV on Day 1, once every 3 weeks for first 4 cycles (each cycle = 21 days).

Also known as: Cis-Diaminedichloroplatinum, CDDP

Atezolizumab with Platinum and Etoposide, followed by cystectomy.

Etoposide DRUG

Etoposide 100 mg/m2 IV on Days 1 - 3 every cycle for the first 4 cycles (each cycle = 21 days)

Also known as: VP-16, VePesid, VP-16-213, EPEG, epipodophyllotoxin, NSC # 141540

Atezolizumab with Platinum and Etoposide, followed by cystectomy.

Cystectomy PROCEDURE

Cystectomy should be performed within 42 days after completion of last administered study therapy of induction phase (first 4 cycles of chemotherapy).

Atezolizumab with Platinum and Etoposide, followed by cystectomy.

Eligibility Criteria

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

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Genentech, Inc.: collaborator

Study Sites (2)

Johns Hopkins University: Sibley Memorial Hospital

Washington D.C., District of Columbia, 20016, United States

RECRUITING

Johns Hopkins University: Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21287, United States

RECRUITING

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

atezolizumab; Carboplatin; Cisplatin; Etoposide; Podophyllotoxin; Cystectomy

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Lignans; Benzyl Compounds; Benzene Derivatives; Urologic Surgical Procedures; Urogenital Surgical Procedures; Surgical Procedures, Operative

Study Officials

• Jean Hoffman-Censits, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Deborah Schwartz, RN

CONTACT

410-502-4523; dschwa27@jhmi.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2022
• First Posted: April 5, 2022
• Study Start: June 27, 2022
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2029
• Last Updated: June 29, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)