A Prospective Study of Neoadjuvant Chemotherapy with Nivolumab/Gemcitabine/Cisplatin in Muscle-Invasive or Locally-Advanced Urothelial Carcinoma of Bladder
- Conditions
- Neoplasms
- Registration Number
- KCT0003804
- Lead Sponsor
- Samsung Medical Center
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 48
1.Subject is at least 20 years of age.
2.Subject has a histologically or cytologically confirmed diagnosis of urothelial carcinoma arising from urinary bladder.
3.Muscle-invasive, high-risk (T3 or T4a) disease with no other treatment options than radical cystectomy.
4.Subject has an ECOG performance status of 0 to 1.
5.Subject has a life expectancy of 6 months or more.
6.At least 2 weeks since the last surgical procedures or biopsies prior to enrolment. Subjects must have recovered to 7.Acceptable liver function:
a.Bilirubin ? 1.5 times upper limit of normal (x ULN); does not apply to subjects with Gilbert’s syndrome diagnosed as per institutional guidelines.
b.AST (SGOT) and ALT (SGPT) ? 3 x ULN
8.Acceptable renal function with serum creatinine ? 1.5 x ULN or a calculated creatinine clearance = 60 mL/min using the Cockcroft-Gault or MDRD formulas.
9.Acceptable hematologic status (without growth factor support or transfusion dependency):
a.ANC ? 1500 cells/µL.
b.Platelet count ? 100,000/µL.
c.Hemoglobin ? 9.0 g/dL.
10.Women of childbearing potential (including women with chemical menopause or no menstruation for other medical reasons)#1 must agree to use contraception#2 from the time of informed consent until 5 months or more after the last dose of the investigational product. Also, women must agree not to breastfeed from the time of informed consent until 5 months or more after the last dose of the investigational product.
11.Men must agree to use contraception#2 from the start of study treatment until 7 months or more after the last dose of the investigational product. Must agree to use an adequate method of contraception if the patient is sexually active, during and for 12 weeks after the completion of chemotherapy.
12.Written and voluntary informed consent understood, signed and dated.
#1: Women of childbearing potential are defined as all women after the onset of menstruation who are not postmenopausal and have not been surgically sterilized (e.g., hysterectomy, bilateral tubal ligation, bilateral oophorectomy). Postmenopause is defined as amenorrhea for ?12 consecutive months without specific reasons. Women using oral contraceptives, intrauterine devices, or mechanical contraception such as contraceptive barriers are regarded as having childbearing potential.
#2: The subject must consent to use any two of the following methods of contraception: vasectomy or condom for patients who are male or female subject’s partner and tubal ligation, contraceptive diaphragm, intrauterine device, spermicide, or oral contraceptive for patients who are female or male subject’s partner.
1.Ongoing treatment with an anticancer agent not contemplated in this protocol.
2.Radiologic finding consistent with extravesical and/or metastatic disease.
3.Severe medical or phychological illness that preclude participation to study, including any history of clinically relevant coronary artery disease or myocardial infarction within the last 3 years, New York Heart Association (NYHA) grade III or greater congestive heart failure, cerebrovascular attack within the prior year, or current serious cardiac arrhythmia requiring medication except atrial fibrillation.
4.Non-tolerable > Grade 2 neuropathy or evidence of unstable neurological symptoms within 4 weeks of Cycle 1 Day 1.
5.Major surgery, other than diagnostic surgery or transurethral resection, within 4 weeks prior to Cycle 1 Day 1, without complete recovery.
– Patients who have received systemic corticosteroids (except for temporary use, e.g., for examination or prophylaxis of allergic reactions) or immunosuppressants within 28 days before randomization
– Patients who have received antineoplastic drugs (e.g., chemotherapy agents, molecular-targeted therapy agents, or immunotherapy agents) within 28 days before randomization
– Patients who have undergone surgical adhesion of the pleura or pericardium within 28 days before randomization
– Patients who have undergone surgery involving local or topical anesthesia within 14 days before Randomization
– Patients who have received radiotherapy within 28days before randomization, or radiotherapy to bone metastases within 14 days before randomization
– Patients who have received any other unapproved drug (e.g., investigational use of drugs, unapproved combined formulations, or unapproved dosage forms) within 28 days before randomization
6.Double primary cancer of other site(s) or a history of other malignancies, except for cured ones at the discretion of investigator.
7.Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy.
8.Subjects who have exhibited allergic reactions to study treatment.
9.Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the Investigator, pose an unacceptable risk to the subject in this study.
10.The subject has legal incapacity or limited legal capacity. Dementia or significantly altered mental status that would limit the understanding or rendering of informed consent and compliance with the requirements of this protocol. Unwillingness or inability to comply with the study protocol for any reason.
11. Patients who have contraindications in the investigational product.
12. Patients with a current or past history of interstitial lung disease or pulmonary fibrosis diagnosed based on imaging or clinical findings. Patients with radiation pneumonitis may be randomized if the radiation pneumonitis has been confirmed as stable (beyond acute phase) without any concerns about recurrence
13. Patients with concurrent diverticulitis or symptomatic gastrointestinal ulcerative disease
14. Patients with a positive test result for any of the following: *HIV-1 antibody, HIV-2 antibody, **HTLV-1 antibody, ***HBs antigen, or ****HCV antibody
15. Patients with a negative HBs antigen test but a positive test result for either HBs antibody or HBc antibody with a detectable level of *****HBV-DNA
* HIV: human immunodeficiency virus
** HTLV: human T-cell leukemia virus
*** HBs: hepatitis B surface
**** HC
Study & Design
- Study Type
- Interventional Study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Radiological and/or physical assessments of the tumor lesions
- Secondary Outcome Measures
Name Time Method Safety evaluation