Tailored ImmunoTherapy Approach With Nivolumab in Subjects With Metastatic or Advanced Transitional Cell Carcinoma (TITAN-TCC)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03219775|
Recruitment Status : Active, not recruiting
First Posted : July 18, 2017
Last Update Posted : November 3, 2021
TITAN-TCC (0416-ASG) is a Phase 2, open-label study of nivolumab (BMS-936558) monotherapy with additional nivolumab/ipilimumab "boost" cycles in previously untreated* and platinum-based pretreated, 2nd and 3rd line, advanced or metastatic transitional cell carcinoma subjects. Nivolumab is a fully human PD-1 antibody which blocks the respective immune checkpoint in a ligand (PD-L1/PD-L2) independent manner.
[*Update from Jan-2020: First-line cohort was stopped and the inclusion of these patients was terminated]
|Condition or disease||Intervention/treatment||Phase|
|Transitional Cell Carcinoma Advanced Cancer Metastatic Cancer||Biological: Nivolumab/Ipilimumab||Phase 2|
This is a Phase 2, single arm study of a tailored immunotherapy approach with nivolumab in adult (≥ 18 years) subjects with previously untreated (1st line)* or pretreated (2nd and 3rd line), surgically unresectable or metastatic TCC (further designated "advanced TCC"). The study targets to recruit 130 untreated (1st line) and 120 pretreated (2nd / 3rd line) patients, respectively. Tumor tissue obtained at least 2 years prior to screening must be available for a central pathology assessment. Subjects must have advanced (not amenable to curative surgery or radiation) or metastatic TCC, and must not have received more than two prior platinum-based chemotherapies for the treatment of advanced TCC.
[*Update from Jan-2020: First-line cohort was stopped and the inclusion of these patients was terminated. According protocol v.5.0 80 2nd/3rd-line patients need to be included]
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||169 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Single Arm Clinical Trial of a Tailored ImmunoTherapy Approach With Nivolumab in Subjects With Metastatic or Advanced Transitional Cell Carcinoma|
|Actual Study Start Date :||July 6, 2017|
|Actual Primary Completion Date :||September 16, 2021|
|Estimated Study Completion Date :||February 18, 2023|
Other Name: Opdivo/Yervoy
- Objective Response Rate (ORR) [ Time Frame: max. months ]The primary objective will be measured by the primary endpoint of ORR (based on investigator assessments) among all treated subjects, first line subjects and second line subjects. It is defined as the number of subjects with a best overall response of CR or PR divided by the number of all treated subjects, first line subjects or second line subjects. Best overall response is defined as the best response designation, as determined by investigator, recorded between the date of first dose and the date of objectively documented immunotherapy resistance per RECIST v1.1 or the date of subsequent therapy, whichever occurs first.
- Remission Rates (RR) [ Time Frame: max. 68 months ]Remission Rates (RR) during TITAN treatment: CR/PR
- Time to Immunotherapy Resistance (TIR) [ Time Frame: max. 68 months ]Time to Immunotherapy Resistance (TIR) will be used as a surrogate parameter of progression free survival using a tailored Immunotherapy regimen with "boost" cycles upon initial progression.
- Time to Response (TTR) [ Time Frame: max. 68 months ]TTR is defined either as the time from first dosing date or initiation of nivolumab/ipilimumab "boost" cycles to the date of the first confirmed response thereafter, as assessed by the IRC. Hence, TTR may be recorded several times per patient.
- Duration of Response (DOR) [ Time Frame: max. 68 months ]DOR is defined as the time from first confirmed response (CR or PR) to the date of the documented progressive disease as determined using RECIST 1.1 criteria or death due to any cause, whichever occurs first. DOR may be recorded multiple times per patient.
- Progression free survival (PFS) [ Time Frame: max. 68 months ]PFS is defined as the time from first dosing date to the date of the first documented tumor progression based on investigator assessments (per RECIST 1.1), or death due to any cause. Clinical deterioration in the absence of unequivocal evidence of progression (per RECIST 1.1) is not considered progression for purposes of determining PFS.
- Overall survival (OS) [ Time Frame: max. 68 months ]OS is defined as the time from first dosing date to the date of death. A subject who has not died will be censored at last known date alive.
- Safety - Incidence of adverse events, serious adverse events, deaths and laboratory abnormalities [ Time Frame: max. 68 months ]Safety and tolerability objective will be measured by the incidence of adverse events, serious adverse events, deaths and laboratory abnormalities. Toxicities will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
- EORTC QLQ-C30 [ Time Frame: max. 68 months ]Questionaires
- EQ-5D [ Time Frame: max. 68 months ]Questionaires
- EQ-5D VAS [ Time Frame: max. 68 months ]Visual analogue scale
- Immune monitoring (Exploratory Endpoint) [ Time Frame: max. 68 months ]Parameters will be analysed with regard to the prediction of response as well as immune related adverse events.
- PD-L1 and PD-L2 [ Time Frame: max. 68 months ]the expression of PD-L1 and PD-L2 in tumor tissues of mTCC patients will be correlated with efficacy parameters.
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): NCT03219775
|Principal Investigator:||Marc-Oliver Grimm, Prof. Dr.||Universitätsklinikum Jena|