Tailored ImmunoTherapy Approach With Nivolumab in Subjects With Metastatic or Advanced Renal Cell Carcinoma (TITAN-RCC)
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|ClinicalTrials.gov Identifier: NCT02917772|
Recruitment Status : Active, not recruiting
First Posted : September 28, 2016
Last Update Posted : August 26, 2019
|Condition or disease||Intervention/treatment||Phase|
|Carcinoma, Renal Cell Clear-cell Metastatic Renal Cell Carcinoma||Biological: Nivolumab/Ipilimumab||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||200 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 Renal Cell Carcinoma|
|Actual Study Start Date :||October 2016|
|Actual Primary Completion Date :||December 2018|
|Estimated Study Completion Date :||July 2021|
Other Name: Opdivo/Yervoy
- Objective Response Rate (ORR) [ Time Frame: until 30 weeks after last patient first treatment, LPFT ]
(RECIST 1.1) by CT or MRI measured at week 8 (+/- 1 week) and week 16 (+/- 1 week), 28 (+/- 1 week) and then every 12 weeks (+/- 1 week).
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. For subjects without documented immunotherapy refractory disease or subsequent therapy, all available response designations will contribute to the ORR determination.
- General considerations: RR, TTR, DoR, PFS, TIR (Time to Immunotherapy Resistance), OS [ Time Frame: until 30 weeks after last patient first treatment, LPFT ]All as assessed by investigators among all treated subjects, first line subjects, and second line subjects. Furthermore, patients with IMDC intermediate and high risk will be analysed separately.
- Remission Rates during TITAN treatment: RR1, RR2, RR2SD, RR3 [ Time Frame: until 30 weeks after last patient first treatment, LPFT ]
- RR1: Number of patients with CR/PR during nivolumab monotherapy (induction and maintenance, the latter only including protocol defined pseudoprogressors) divided by all treated patients.
- RR2: Remission rate after progression during nivolumab monotherapy. It is defined as the number of patients with CR/PR after receiving nivolumab/ipilimumab "boost" cycles for initial progression during nivolumab monotherapy divided by all patients receiving "boosts" for this situation.
- RR2SD: Remission rate after stable disease during nivolumab monotherapy. It is defined as the number of patients with CR/PR after receiving nivolumab/ipilimumab "boost" cycles for initial stable disease during nivolumab monotherapy divided by all patients receiving "boosts" for this situation.
- RR3 is the subsequent remission event to RR2 for patients undergoing repeated nivolumab/ipiliumumab "boost" according to the algorithm described above.
- Time to Immunotherapy Resistance: TIR [ Time Frame: Time from first dosing date to the date of documented tumor progression based on investigator assessments (per RECIST 1.1) despite 4 "boost" cycles or within 3 months after the last "boost" cycle, or death due to any cause. ]Subjects with disease progression despite 4 nivolumab/ipilimumab combination "boost" cycles or within 3 months after the last "boost" cycle will be considered immunotherapy resistant.
- Time-to-Response: TTR [ Time Frame: 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. ]TTR may be recorded several times per patient.
- Duration of Response: DOR [ Time Frame: 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.
- Overall survival:OS [ Time Frame: Time from first dosing date to the date of death. A subject who has not died will be censored at last known date alive. ]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: Adverse events assessment [ Time Frame: Continuously: Treatment Visit day 1/week 1 until Survival Visits/Follow-up Visits ]Treatment Emergent Adverse Events according to CTC 4
- Safety: Frequency of abnormal laboratory parameters [ Time Frame: Screening Visit until Survival Visits/Follow-up Visits ]
Treatment Period: Within 72 hrs prior to re-dosing to include CBC w/ differential, AST, ALT, ALP, T.Bili, BUN or serum urea level, creatinine. Ca, Mg, Na, K, Cl, LDH, glucose, amylase, lipase, TSH (with reflexive Free T4 and Free T3).
Follow-up Period: On site/local CBC w/differential, AST, ALT, ALP, T.Bili, BUN or serum urea level, creatinine and TSH for X01, repeat at X02 if study drug related toxicity persists.
- Patient reported outcomes [ Time Frame: Treatment Visit day 1/week 1 until Survival Visits/Follow-up Visits 1 and 2 ]NCCN-FACT FKSI-19 (Version 2)
- Exploratory objectives: Immune monitoring [ Time Frame: Taken together with Laboratory Tests: Prior to induction (Baseline), Prior to Nivo dose 4, Prior to Nivo dose 8, Prior to 6th nivo maintenance dosing ]
To monitor immunogenicity of nivolumab and nivolumab/ipilimumab "boosts" with regard to prediction of response as well as immune related adverse events, including:
- frequency, differentiation and activation of blood-circulating CD4+ and CD8+ T cells (CD27, CD28, CD45RA, CD45RO, CD57, CD95, CD69, CD25, IFN-γ, TNF- α, IL-4, IL 17, IL-10, CD107a)
- frequency of blood-circulating dendritic cells (HLA-DR, slan, CD1c, CD11c, CD123, CD141, CD303), myeloid-derived suppressor cells (HLA-DR, CD11b, CD14, CD15, CD33), and regulatory T cells (FoxP3, CD25, CD45RA, CD127)
- expression of molecules involved in immune checkpoint modulation (ICOS, PD-1, PD-L1, CTLA-4) on blood-circulating dendritic cells and T cells
- To determine the presence of autoantibodies in the serum of RCC patients
- To explore the expression of PD-L1 and PD-L2 in tumor tissues of mRCC patients and correlation 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): NCT02917772
|Principal Investigator:||Marc-Oliver Grimm, Prof.||Universitätsklinikum Jena|