A Study of Experimental Gemcitabine Hydrochloride and Cisplatin For Invasive Bladder Urothelial Cancer

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Age: 18 years or older
Gender:
Any
Healthy Volunteers: No
Keywords: bladder cancer, bladder removal, muscle-invasive bladder cancer
Type: Drug study, Phase 2
Target:
5 Participants
Investigator:
Description
The purpose of this study is to see if some patients with muscle-invasive bladder cancer can avoid surgery to remove their bladder. New research has shown that bladder tumors with changes in the DDR genes are very sensitive to a certain chemotherapy treatment. This treatment is known as dose-dense gemcitabine and cisplatin (ddGC).

In this study, we are studying patients whose tumors have a DDR gene mutation. Their bladder tumor has shrunk after chemotherapy. We want to learn if they can keep their bladder and avoid a removal surgery called a radical cystectomy. The study doctors hope to learn whether this approach is better or worse than the usual treatment.
This study requires

The study team will make sure you qualify to take part in the study. Qualified participants will receive detailed information about the study. This may include a list of study-related tests and procedures.

Who can participate

Eligibility Criteria

Documentation of Disease

  • Histologically confirmed muscle-invasive urothelial carcinoma of the bladder. Urothelial carcinoma invading into the prostatic stroma with no histologic muscle invasion is allowed, provided the extent of disease is confirmed via imaging and/or EUA. The diagnostic TURBT sample must have been obtained within 60 days prior to registration.

  • 20 unstained slides (10 micron thickness) of formalin-fixed paraffin-embedded (FFPE) pre-treatment diagnostic transurethral resection (TUR) specimen available (for sequencing), with 2 (5 micron) slides at the start and end of the 20 slides, for a total of 22 unstained slides. An FFPE block is also acceptable.

  • Clinical stage T2-T4aN0/xM0 disease

  • Medically appropriate candidate for radical cystectomy as assessed by surgeon

  • No concomitant multifocal carcinoma in situ; a single focus is allowed

  • One focus of muscle-invasive bladder cancer and/or a tumor <5 cm in size

  • No clinical or radiographic evidence for locally advanced or metastatic disease

Prior Treatment

  • No prior anti-PD-1, anti PD-L1 therapies, or systemic chemotherapy (prior intravesical induction immunotherapy for non-muscle invasive disease is allowed, defined as BCG x6 treatments; BCG refractory disease, defined as disease recurrence within 3 months of BCG therapy, is not allowed)

  • No prior radiation therapy to the bladder

  • No major surgery or radiation therapy <4 weeks of registration

Not pregnant and not nursing This study involves an agent that has known genotoxic, mutagenic and teratogenic effects. For women of childbearing potential only, a negative pregnancy test done ≤ 14 days prior to registration is required.

Age ≥ 18 years

ECOG Performance Status 0-1

Required Initial Laboratory Values:

  • Absolute Neutrophil Count (ANC) ≥ 1,000/mm3

  • Platelet Count ≥ 100,000/mm3

  • Calculated creatinine clearance ≥ 55 mL/min

  • Total Bilirubin ≤ 1.5 x upper limit of normal (ULN)

  • (For patients with documented Gilbert’s syndrome Bilirubin ≤ 3 x ULN)

  • AST / ALT ≤ 2.5 x ULN

  • Alkaline Phosphatase ≤ 2.5 x ULN

Comorbid conditions

  • No hydronephrosis refractory to urinary diversion

  • No evidence of NYHA functional class III or IV heart disease

  • No ongoing cardiac dysrhythmias of NCI CTCAE Version 5.0 grade >2

  • No pre-existing sensory grade >2 neuropathy

  • No pre-existing grade >2 hearing loss

  • No serious intercurrent medical or psychiatric illness, including serious active infection

  • None of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attack

  • No known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness or other active infection. HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with the drugs used in this trial. In addition, these patients are at increased risk of lethal infections when treated with marrowsuppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy, when indicated.

  • No history of allergic reaction attributed to compounds of similar chemical or biologic composition to the agents used in this study.

  • No concurrent treatment on another clinical trial; supportive care trials or nontherapeutic trials (e.g., quality of life) are allowed.

  • No prior malignancy except for: adequately treated basal or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years. Patients with localized prostate cancer who are being followed by an active surveillance program are also eligible.

  • Patients must have completed 4 or more cycles of protocol-directed chemotherapy.

  • Deleterious alteration within 1 or more of 9 pre-defined DDR genes within the pretreatment TURBT DNA

  • Cystoscopy and imaging performed to determine stage/treatment assignment.

Benefits and risks of participating
BENEFITS:

We cannot promise any benefits to you as a result of taking part in this research study.


RISKS:

The study doctor will discuss the risks associated with taking part in this research study.
Compensation
You will not be paid to take part in this research study.
Resources
Schedule
Study duration and period
You will receive the study treatment for about 12 weeks. After you finish your treatment, your doctor and study team will follow you to see if the cancer returns. All patients will get scans every 3 months the first 2 years, yearly for years 3-5. Patients who do not have surgery will be followed with a cystoscope every 3 months for 2 years, every 6 months during years 3 and 4, and then once during year 5. You will keep seeing your doctor for up to 5 years after treatment. For patients who have surgery, you will see your doctor every time you get a scan (every 3 months for 2 years, then yearly for years 3-5).
Recruitment period
From Sept. 17, 2018
Location
UC Davis Comprehensive Cancer Center
4501 X Street
Sacramento, CA 95817
Research Topic
Conditions:
  • Infiltrating Bladder Urothelial Carcinoma
  • Stage II Bladder Urothelial Carcinoma
  • Stage III Bladder Urothelial Carcinoma

Have any questions or want to learn more? Leave your contact details below and the research team will reach out to you.


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