A Study of Risk Enabled Therapy After Neoadjuvant Immunochemotherapy for Bladder Cancer
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|ClinicalTrials.gov Identifier: NCT04506554|
Recruitment Status : Recruiting
First Posted : August 10, 2020
Last Update Posted : March 17, 2021
|Condition or disease||Intervention/treatment||Phase|
|Muscle-Invasive Bladder Carcinoma||Drug: AMVAC + Nivolumab||Phase 2|
Muscle invasive bladder cancer (MIBC) constitutes 20-25% of all cases with 5 year survival estimated at 45% regardless of treatment.1-4 Although neoadjuvant cisplatin-based chemotherapy (NAC) followed by a radical cystectomy or cystoprostatectomy with a lymph node dissection is the preferred treatment choice for MIBC in the United States, there are several drawbacks and challenges with this approach. Patients must be fit to undergo a surgical intervention. Grade 2 through 5 complications have been documented in 53% of patients undergoing cystectomy at a tertiary care center, and the surgical mortality rate is 1.5%.5, 6 Furthermore, urinary diversion commonly requires an ileal conduit and an external appliance, impacting patient's quality of life.
By incorporating neoadjuvant nivolumab with AMVAC, our goal in RETAIN-2 is to increase the number of patients who would be eligible for bladder preservation while maintaining the long-term oncologic outcomes. Nivolumab, an anti-PD1 therapy, is FDA approved for treatment of metastatic urothelial carcinoma post platinum-based chemotherapy.20 Recently, neoadjuvant pembrolizumab (anti-PD1) and atezolizumab (anti-PDL1) was tested in MIBC in the PURE-01 and ABACUS studies, and a pT0 rate of 38.6% and 29%, respectively, was achieved.21, 22 Additionally, recent work by Kim et al. presented at AACR 2019 demonstrated that AMVAC induces gene signatures in luminal tumors and may have a synergistic response with immunotherapy. Given the impressive activity of both AMVAC and nivolumab in the neoadjuvant setting, in this study the investigators hypothesize that using the combination of neoadjuvant nivolumab and AMVAC will lead to higher cT0 rate and metastasis-free survival at 2 years. At the same time by using the risk adapted strategy, a select group of patients will be able to preserve their bladders and significantly improve their quality-of-life.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||71 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Trial of Risk Enabled Therapy After Neoadjuvant Immunochemotherapy for Bladder Cancer|
|Actual Study Start Date :||December 1, 2020|
|Estimated Primary Completion Date :||November 2022|
|Estimated Study Completion Date :||November 2023|
Experimental: AMVAC + nivolumab
This will be a single-arm, open-label, multicenter phase 2 study of neoadjuvant nivolumab with AMVAC. Approximately 70 evaluable patients will be enrolled into this study. Eligible patients will be those with diagnosis of muscle invasive urothelial carcinoma of the bladder who are cT2 or cT3 but not clinical N1 at diagnosis. Clinical stage is confirmed by transurethral resection of bladder tumor (TURBT#1).
Drug: AMVAC + Nivolumab
Nivolumab 240mg will be administered intravenously for 3 doses - on days 1, 15 and 29. AMVAC will be dosed intravenously every 2 weeks for 3 doses on days 1, 15 and 29 with Neulasta or equivalent. Standard AMVAC dose is as follows: methotrexate 30mg/m2, vinblastine 3mg/m2, doxorubicin 30mg/m2, and cisplatin 70mg/m2.
- Incidence of Metastasis-free survival (MFS) [ Time Frame: 2 years ]MFS is defined as a recurrence of urothelial carcinoma that is >cN1 (more than one clinically suspicious pelvic lymph node) or surgically unresectable local recurrence (e.g., >cT4a) or M1 disease.
- Number of days of Overall survival [ Time Frame: up to 5 years ]Overall Survival (OS) will be defined as the number of days from study entry to death. Individuals who are alive at last contact will be censored on the date of last contact.
- Number of days of Progression free survival [ Time Frame: up to 5 years ]Progression Free Survival (PFS) for this study will be defined as the number of days from study entry to date of first evidence of tumor progression (presence of muscle invasive disease, nodal or distant recurrence) or until death from any cause, whichever comes first. Individuals that are alive and remain free of muscle invasive disease, nodal recurrence and distant disease recurrence will be censored on the date of last clinical visit.
- Number of patients erporting Toxicity of neoadjuvant nivolumab and AMVAC therapy [ Time Frame: until 100 days after the last nivolumab/AMVAC ]
Toxicity, AEs, SAEs for all patients that are associated with nivolumab or AMVAC will be collected/reported at each cycle and until 100 days after lastnivolumab/AMVAC.
Toxicity, AEs, SAEs for the CRT arm specifically will be collected/reported as follows. Grade 1-5 toxicity at C1 (start of nivolumab/AMVAC), C2 (second cycle ofnivolumab/AMVAC), C3 (third cycle of nivolumab/AMVAC), start of chemoradiation, 1/2 completion chemoradiation, completion of chemoradiation, and up to 30 days after completion of chemoradiation.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04506554
|Contact: Pooja Ghatalia, MD||215-728-3889||Pooja.Ghatalia@tuhs.temple.edu|
|Contact: Daniel Geynisman, MDemail@example.com|
|United States, Pennsylvania|
|Fox Chase Cancer Center - Philadelphia||Recruiting|
|Philadelphia, Pennsylvania, United States, 19111-2497|
|Contact: Pooja Ghatalia, MD Pooja.Ghatalia@tuhs.temple.edu|
|Principal Investigator:||Pooja Ghatalia, MD||Fox Chase Cancer Center|