Histologically documented urothelial carcinoma (squamous differentiation or mixed cell types allowed).
Must have a histologically confirmed transitional cell carcinoma (TCC, also known as urothelial carcinoma), locally advanced or metastatic
Histologically confirmed muscle-invasive urothelial carcinoma of the bladder or upper tract; variant histology allowed as long as urothelial carcinoma is predominant (> 50%); pure small-cell carcinoma is excluded
Patients must not have had urothelial carcinoma in the prostate or upper urinary tract within the previous 24 months, or muscle invasive urothelial carcinoma of the bladder at any time; patients must have a computed tomography (CT) or magnetic resonance imaging (MRI) of the abdomen and pelvis to rule out upper tract malignancy and intra-abdominal metastases within 90 days prior to registration
Patients must have histologically proven Ta, carcinoma in situ (CIS) or T1 stage urothelial cell carcinoma of the bladder within 90 days prior to registration
Histologically confirmed diagnosis of urothelial carcinoma of the bladder. Variant histology is acceptable if there is a predominant urothelial component.
Urothelial carcinoma
All subjects must have previously treated either locally advanced or metastatic renal or urothelial cell carcinoma to be eligible for participation
Urothelial carcinoma;
Bladder urothelial carcinoma
Adequately treated urothelial papillary non-invasive carcinoma or carcinoma in situ
Patients must have histologically proven urothelial carcinoma of the bladder; those with mixed histology, including a component of urothelial carcinoma, are eligible; pure small cell carcinoma, pure adenocarcinoma, and pure squamous cell carcinoma are excluded
Patients must not have received previous systemic cytotoxic chemotherapy for urothelial carcinoma
Concomitant upper tract urothelial carcinoma
Histologic evidence of urothelial carcinoma of the bladder
Low/intermediate-risk papillary urothelial carcinoma of the bladder, at initial occurrence or recurrent with > 6 months interval free of disease
Diagnosis of urothelial carcinoma involving the prostatic urethra or upper urinary tract
Patients must have histologically or cytologically confirmed urothelial tract carcinoma; patients with urothelial carcinoma of the bladder, upper tract, or urethra are eligible
Predominant histologic component (> 50%) must be urothelial (transitional cell) carcinoma
Localized urothelial cancer of bladder with presence of transitional cell carcinoma (TCC) component; mixed histologies are allowed
Biopsy taken from one or more tumors located above the ureteropelvic junction (UPJ) showing LG urothelial carcinoma. Diagnosed not more than 2 months prior to the screening.
Patient has a history of invasive urothelial carcinoma in the urinary tract during the past 5 (Five) years.
Patient has a history of high grade papillary urothelial carcinoma in the urinary tract during the past 2 (Two) years.
Evidence of non-bladder urothelial (transitional cell) carcinoma by biopsy, cytology, or radiological imaging within the past 2 years of treatment (e.g. upper tract transitional cell carcinoma, urethral urothelial carcinoma)
Histological or cytologically proven urothelial carcinoma; mixed urothelial/non-urothelial cell histologies are allowed but pure non-urothelial cell carcinoma is NOT allowed
Patient has ever had confirmed extravesical urothelial disease (upper tract and urethral including prostatic urethral)
Subjects must have a histologic diagnosis of urothelial carcinoma with radiologic, histologic or cytologic evidence of metastatic disease
Has positive urine cytology for urothelial malignancy at screening.
Adequately treated urothelial papillary noninvasive carcinoma or carcinoma in situ.
Muscle invasive (T2 or above) urothelial carcinoma or urothelial carcinoma outside the bladder
Histologically confirmed muscle-invasive urothelial carcinoma of the bladder defined as T2-T4 stage; mixed histologies are acceptable provided urothelial carcinoma is the predominant histology (? 50%); patients with > 50% non- urothelial carcinoma histologies or any component of small cell carcinoma are not eligible; resectable clinical node-positive (N1) patients are eligible provided the lymph nodes are confined to the true pelvis and are within the planned surgical lymph node dissection template
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)
Patients must have histologic proof of urothelial cancer; this includes bladder cancer, in addition to other tumors of the urothelial lining including renal pelvis, ureteral, and urethral cancer; upper tract urothelial carcinoma will also be included; this group may include any patient requiring cystectomy, including muscle invasive disease (cT2-3aN0M0), whose tumor could not be completely removed at transurethral resection
Any evidence of metastatic urothelial carcinoma
PHASE I AND II SCLC AND UROTHELIAL CARCINOMA EXPANSION COHORT: Patients who are receiving any other investigational agents
UROTHELIAL CARCINOMA EXPANSION COHORT ONLY: Patients who have had prior treatment with olaparib or other camptothecin inhibitors
PHASE I AND II SCLC AND UROTHELIAL CARCINOMA EXPANSION COHORT: Hypersensitivity to study therapies and its excipients
PHASE I AND II SCLC AND UROTHELIAL CARCINOMA EXPANSION COHORT: Any chronic or concurrent acute liver disease
UROTHELIAL CARCINOMA EXPANSION COHORT: Prior antiangiogenic therapy are permitted (2-week washout from therapy is required)
UROTHELIAL CARCINOMA EXPANSION COHORT: ECOG 0–2
UROTHELIAL CARCINOMA EXPANSION COHORT: Leukocytes >= 3,000/mcL
Primary urothelial or predominantly urothelial carcinoma of the bladder
Has histologically confirmed urothelial carcinoma of the bladder; those with mixed histology, including a component of urothelial carcinoma, are eligible; pure small cell carcinoma, pure adenocarcinoma, and pure squamous cell carcinoma are excluded
Has had no prior systemic cytotoxic chemotherapy for urothelial carcinoma (prior intravesicular chemotherapies are permitted)
Has received prior radiation therapy to the bladder for the purpose of treating urothelial carcinoma
Evidence of upper tract urothelial carcinoma
Have locally advanced or metastatic urothelial cancer that is not amenable to curative surgical treatment\r\n* Have histologically or cytologically confirmed urothelial tract carcinoma
Pathologic diagnosis of urothelial or squamous cell carcinoma of the bladder
cT2/T3-N0-M0 urothelial carcinoma of the bladder
More than two prior lines of systemic anti-cancer therapy for urothelial carcinoma
Prior systemic chemotherapy for urothelial cell carcinoma of the bladder.
Absence of concomitant upper tract urothelial carcinoma (i.e. cancer within the kidney or ureter) as evidenced on computed tomography (CT) urogram and no visible lesion and/or biopsy proven evidence of urothelial carcinoma within the prostatic urethra (i.e. biopsy proven presence of cancer within the prostatic urethra)
Pathologically proven (either histologic or cytologic) diagnosis of urothelial carcinoma
Upper tract urothelial carcinoma
Patients must have histologically or cytologically confirmed metastatic urothelial carcinoma; urothelial cancer derived from the bladder, ureter or upper tract is permitted
Metastatic or inoperable urothelial cancer
Patients must have histologically confirmed urothelial carcinoma that is advanced or metastatic
Patients with active malignancies in addition to urothelial carcinoma
Absence of concomitant upper tract urothelial carcinoma or urothelial carcinoma within the prostatic urethra. Freedom from upper tract disease (if clinically indicated) as indicated by no evidence of upper tract tumor by either intravenous pyelogram, retrograde pyelogram, computed tomography (CT) scan with or without urogram, or MRI with or without urogram performed within 6 months of enrollment
History of malignancy of other organ system within past 5 years, except treated basal cell carcinoma or squamous cell carcinoma of the skin and ? pathological tumor-2 (pT2) upper tract urothelial carcinoma at least 24 months after nephroureterectomy. Also patients with genitourinary cancers other than urothelial cancer or prostate cancer that are under active surveillance are excluded (see inclusion criterion 9)
Patients must have histologically proven urothelial carcinoma of the bladder; those with mixed histology, including a component of urothelial carcinoma, are eligible; small cell carcinoma, pure adenocarcinoma, and pure squamous cell carcinoma are excluded
Patients must not have received previous systemic cytotoxic chemotherapy for urothelial carcinoma
Has received no prior systemic chemotherapy for advanced or metastatic urothelial carcinoma, with the following exceptions:
For urothelial carcinoma:
For RCC, urothelial carcinoma, and gastric or GEJ adenocarcinoma, hemoglobin ?8.0 g/dL
For urothelial carcinoma, prior treatment with any taxane
Concomitant bladder urothelial carcinoma is acceptable if it is organ confined and surgically resectable
Subjects with urothelial carcinoma:
Adequately treated urothelial papillary non-invasive carcinoma or carcinoma in situ
For Phase 2, subjects with the following tumor types who meet protocol-defined criteria: advanced or metastatic NSCLC, melanoma, urothelial carcinoma, SCCHN, SCLC, and CRC.
Patients with any component of small cell carcinoma are not eligible; other variant histologies are permitted provided the predominant (>= 50%) subtype is urothelial carcinoma
Patients must be able to provide a sufficient biopsy sample to the central pathologist for histopathologically confirmed, transitional cell (urothelial) carcinoma. Urothelial tumors with mixed histology (but with <50% variant) are eligible.
Any primary site of urothelial carcinoma including upper tract, renal pelvis, bladder, and ureters
Prior therapy with ? 1 systemic chemotherapy regimens for urothelial carcinoma
Pathologically proven diagnosis of carcinoma of the bladder within 105 days prior to registration\r\n* Operable patients whose initial tumor is a primary high grade urothelial carcinoma of the bladder exhibiting histologic evidence of invasion into the lamina propria (disease clinical stage T1) or a high grade stage Ta urothelial carcinoma without hydronephrosis; patients who have involvement of the prostatic urethra with urothelial carcinoma and have no evidence of stromal invasion of the prostate remain eligible; if the patient’s initial tumor was a high grade stage Ta urothelial carcinoma then his/her recurrent tumor must be a high grade stage T1 urothelial carcinoma to be eligible
Urothelial Carcinoma
The patient must have a pathologically confirmed diagnosis of urothelial BLC, which is currently Stage 4 disease.
A patient with urothelial carcinoma with variant histologic differentiation (e.g. squamous cell differentiation, glandular differentiation, neuroendocrine differentiation) will be eligible provided that the predominant histology is urothelial carcinoma.
Patient must have a diagnosis with urothelial carcinoma of the bladder with clinically apparent tumor Ta, G1-G2.
Patients must have histologically-proven (T2, T3, or T4a) urothelial carcinoma of the bladder (UCB) that requires primary radical cystectomy for definitive treatment; patients must not have clinical stage consistent with a low-risk of node metastasis (carcinoma in situ [CIS] only, T1); patients with a T4b (fixed lesion) are not eligible for this study; NOTE: Patients with predominant urothelial carcinoma with elements of adenocarcinoma, squamous cell carcinoma, micropapillary or minor components of other rare phenotypes are eligible; patients with predominantly small cell, squamous cell, or adenocarcinoma histologies are not eligible; patients with other non-urothelial cancers are not eligible (e.g., sarcoma, lymphoepithelial, nested variant); clinical stage is based on all of the following: transurethral resection of bladder tumor(s) (TURBT[s]) that determined the need for cystectomy, bimanual exam and cross sectional imaging
Patients must have histologically or cytologically confirmed urothelial tract carcinoma
Histologically or cytologically confirmed urothelial carcinoma.
Patients must have undergone a radical cystectomy (reconstructed urinary diversion may be non-continent diversions (eg, ileal conduits) or continent non-orthotopic catheterizable diversions (eg, Indiana pouch) or continent orthotopic diversions (eg, Studer pouch or neobladder) for urothelial bladder carcinoma within 105 days prior to registration; final cystectomy pathology must be either pure urothelial carcinoma or dominant urothelial carcinoma with admixture of other histologies excluding small cell variants\r\n* Neoadjuvant (preoperative) or adjuvant (postoperative) chemotherapy for the bladder cancer is permitted; however, all patients, even those who will receive adjuvant chemotherapy must be registered within 105 days after completing cystectomy regardless of whether adjuvant chemotherapy has started; patients who will then receive adjuvant (postoperative) chemotherapy will be randomized within 28 days of completing chemotherapy
Diagnosis of urothelial carcinoma
Participants must have received prior systemic chemotherapy treatment for metastatic urothelial carcinoma. NOTE: Up to 2 prior systemic chemotherapeutic regimens given in the metastatic disease setting for urothelial carcinoma are allowed.
Histologically proven recurrent urothelial carcinoma of the bladder or prostatic urethra, Stage Tis, Ta
Pure small cell histologic variant or other pure non-urothelial carcinomas
Prior systemic chemotherapy for transitional cell carcinoma of the bladder. Any other prior systemic chemotherapy for a non-urothelial carcinoma must have been completed > 5 years prior to initiation of study.
Any male or female patient diagnosed with incident or recurrent Urothelial Cell Carcinoma and undergoing surveillance at 3 month intervals.
Has had all urothelial cell carcinoma tumor resected within the past 12 months
Planning to undergo radical cystectomy or chemotherapy-radiation for Urothelial Cell Carcinoma
Must have diagnosis of urothelial cancer
Histologic or imaging evidence of urothelial carcinoma of the bladder
Urothelial cancer.
Malignancies other than urothelial carcinoma within 5 years prior to Cycle 1, Day 1
Clinical stage T2-T4a, N0, M0 urothelial bladder cancer