The expansion study was a Phase I, multicenter, open label feasibility trial to characterize the pharmacologic activity of IV CPX-POM in bladder tumor tissues obtained from patients with MIBC (Stage ≥T2, N0-N1, M0) who were scheduled for RC with bilateral (standard or extended) pelvic lymph node dissection (PLND). The Dose Escalation study was a Phase I, multicenter, open label, dose escalation study to evaluate the DLTs and MTD and to determine the recommended Phase 2 dose (RP2D) of CPX-POM administered IV in patients with any histologically- or cytologically-confirmed solid tumor type and was completed.
The expansion cohort of this study was conducted at up to 3 study sites. It was an open-label feasibility trial to characterize the pharmacologic activity of IV CPX-POM in bladder tumor tissues obtained from patients with MIBC (Stage ≥T2, N0-N1, M0) who were scheduled for RC with bilateral (standard or extended) pelvic lymph node dissection (PLND). Both cisplatin eligible and chemotherapy eligible MIBC patients scheduled for RC were eligible to participate. Neoadjuvant treatment with CPX-POM, whether alone or in combination with gemcitabine +cisplatin, started within 8 weeks of transurethral resection of the bladder tumor (TURBT) that showed muscularis propria invasion. Nine patients, four cisplatin-ineligible, and five chemotherapy-eligible patients, were enrolled. Patients who are cisplatin-ineligible were treated with two 21-day treatment cycles of CPX-POM alone (Cycle 1, Days 1-5 treatment, rest days 6-21; Cycle 2, Days 22-26 treatment, rest days 27-43) before a planned RC. Chemotherapy-eligible patients received neoadjuvant chemotherapy (gemcitabine + cisplatin in three 21-day treatment cycles) in combination with three 21-day treatment cycles of CPX-POM (Cycle 1, Days 1-5 treatment, rest days 6-21; Cycle 2, Days 22-26 treatment, rest days 27-42; Cycle 3, Days 43-47, rest days 48-63), i.e. concurrently with the prescribed chemotherapy. The cisplatin + gemcitabine dosing regimen for chemotherapy-eligible patients in the Expansion Cohort was administered per the institution's standard of care. After each infusion of CPX-POM at the RP2D of 900 mg/m2,, patients remained in the clinic for at least a 1-hour observation period. On Day 1 of Cycle 1, single blood and clean catch urine samples were collected prior to the first CPX-POM infusion. On Day 5 of Cycle 1, serial blood and complete urine samples were collected over 24 hours following the fifth, once daily CPX-POM RP2D dose of 900 mg/m2 infused over 20 minutes.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
9
CPX-POM
University of Kansas Medical Center
Kansas City, Kansas, United States
Determine Disease Response Following 2 or 3 CPX-POM Treatment Cycles by Assessing the Complete and Partial Pathologic Response Rate at the Time of Radical Cystectomy (RC)
Tumors will be assessed in a standard manner and given grade/stage according to the American Joint Commission on Cancer (AJCC) criteria. Efficacy will be assessed based on pathologic criteria and evidence of pharmacologic activity in the target tissue.
Time frame: 56 days
Immunohistochemistry (IHC) Analyses of Pre-treatment (at TURBT) and Post-treatment (at Radical Cystectomy) Bladder Tumor Tissues Were Performed to Determine Whether Neoadjuvant Fosciclopirox Treatment Affected the Notch Cell Signaling Pathway.
Immunohistochemistry (IHC) analyses of pre-treatment (at TURBT) and post-treatment (at radical cystectomy) bladder tumor tissues were performed to determine whether neoadjuvant fosciclopirox treatment affected the Notch cell signaling pathway. Immunohistochemistry staining intensity score as a measure of protein expression with four categories: negative (0), weak (1), moderate (2), and strong (3). Staining intensity scores were assigned by a blinded pathologist who specializes in genitourinary cancers. Pre-treatment and post-treatment bladder tumor samples were available for IHC analysis for six of the nine patients studied. For two patients, pre-treatment bladder tumor tissue samples obtained from TURBT at referring sites were not processed for IHC analysis. One patient was discovered to have metastatic MIBC after enrollment, and therefore, did not undergo RC, hence, no post-treatment sample was available for IHC analysis.
Time frame: 56 days
Number of Participant With Any Serious Adverse Events (SAEs) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE Version 4.03)
Incidence of Serious Adverse Events in subjects receiving CPX-POM.
Time frame: 56 days
Number of Participant With Any Adverse Events (AEs) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE Version 4.03)
Incidence of Adverse Events in subjects receiving CPX-POM.
Time frame: 56 days
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