Neo-Adjuvant Bladder Urothelial Carcinoma COmbination-immunotherapy (NABUCCO)
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|ClinicalTrials.gov Identifier: NCT03387761|
Recruitment Status : Recruiting
First Posted : January 2, 2018
Last Update Posted : November 14, 2018
|Condition or disease||Intervention/treatment||Phase|
|Urothelial Carcinoma||Drug: Ipilimumab Drug: Nivolumab||Phase 1|
This is a Phase Ib single-arm trial to evaluate the safety of short-term preoperative therapy with ipilimumab and nivolumab in patients with high-risk resectable urothelial cancer (upper urinary tract allowed), defined as:
- cT3-4aN0M0 OR
The primary endpoint of this trial is safety. We will determine the number of patients that have surgical resection <12 weeks from first infusion, as this is an endpoint that is clinically meaningful for this population. Patients will be receiving:
- Day 1: Ipilimumab 3 mg/kg (wk1)
- Days 22: Ipilimumab 3 mg/kg + Nivolumab 1 mg/kg (wk4)
- Day 43: Nivolumab 3 mg/kg (wk 7)
- Day 57-71: Radical cystectomy or nefro/ureterectomy with appropriate lymph node dissection (wk9-11) After 8 patients have been followed until resection, a report of observed toxicity will be submitted to the DSMB. Enrollment will continue until 12 patients have been enrolled. At this point, an update of toxicity will be sent to the DSMB. If toxicity is judged by the DSMB as manageable, enrolment will continue to a total of 24. CT scans will be required at baseline and week 7- 9 to evaluate response to immunotherapy.
An optional MRI assessment for translational purposes will be scheduled prior to first infusion and week 7-9.
After surgery, patients attend study visits at day 8 and day 29 . Their final study visit for physical examination and laboratory testing is at day 57 (+/- 7 days), which is scheduled to anticipate late-onset adverse events (particularly endocrine).. After this final visit, patients will be followed according to standard clinical guidelines. Tumor biopsies/material preservation is required at baseline and during surgery.
An important secondary endpoint is translational. The main testable hypothesis is that a significant percentage of nonresponse can be explained by immune-inhibitory processes. Absence of immune infiltrates, presence of significant numbers of regulatory T-cells and presence of significant numbers of myeloid-derived suppressor cells will be compared between responders and nonresponders. The efficacy will be defined as the percentage of pathological complete response (pCR) at cystectomy (secondary endpoint).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||24 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Single-arm open clinical trial|
|Masking:||None (Open Label)|
|Official Title:||Phase 1B Study to Assess Safety and Efficacy of Neo-Adjuvant Bladder Urothelial Carcinoma COmbination-immunotherapy (NABUCCO)|
|Actual Study Start Date :||January 15, 2018|
|Estimated Primary Completion Date :||June 1, 2020|
|Estimated Study Completion Date :||December 1, 2020|
Experimental: Ipilimumab + Nivolumab
Day 1: Ipilimumab 3 mg/kg i.v. Days 22: Ipilimumab 3 mg/kg + Nivolumab 1 mg/kg i.v. Day 43: Nivolumab 3 mg/kg i.v.
Day 1: Ipilimumab 3 mg/kg Days 22: Ipilimumab 3 mg/kg
Days 22: Nivolumab 1 mg/kg Day 43: Nivolumab 3 mg/kg
- Number of patients that have surgical resection <12 weeks after study start [ Time Frame: At 12 weeks ]Percentage of patients that underwent surgery within 12 weeks after study start will be assessed
- Efficacy of immunotherapy, assessed by by the percentage of pathological complete response rate (pCR) at cystectomy [ Time Frame: At 12 weeks ]pCR rate after cystectomy according to pathological response criteria
- Differences in immune infiltrates in responders vs nonresponders [ Time Frame: At 12 weeks ]Resistance mechanisms are explored by comparing immune (cell) infiltrates in responders and nonresponders in pre- and post treatment tissue [Multiplex immunohistochemistry, RNA seq]
- T-cell (dys)functionality as measured by comparing the transcriptome of tumor-specific T cells in intra-patient pre- and post therapy tissue [ Time Frame: At 12 weeks ]This component is done in a minority of patients on T cell lysates if a re-TUR (transurethral resection) pre-treatment was done.
- Explore whether radiomics-based predictive models can be established for immunotherapy responders vs non-responders [ Time Frame: at 12 weeks ]CT and MRI images will be assessed in this manner to optimize recognition of an immunotherapy response.
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): NCT03387761
|Contact: Michiel MS van der Heijden, Dr.||+3120 512 firstname.lastname@example.org|
|Contact: Nick N van Dijk, M.D.||+3120 512 email@example.com|
|Antoni van Leeuwenhoek ziekenhuis||Recruiting|
|Amsterdam, NH, Netherlands, 1066CX|
|Contact: Nick van Dijk, MD +31205121664 firstname.lastname@example.org|
|Contact: Michiel van der Heijden, MD, PhD +31205128243 email@example.com|
|Principal Investigator:||Michiel MS van der Heijden, Dr.||NKI-AvL|