DURvalumab in Combination With S-488210/S-488211 vAccine in Non-muscle Invasive Bladder CancEr (DURANCE)
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|ClinicalTrials.gov Identifier: NCT04106115|
Recruitment Status : Not yet recruiting
First Posted : September 26, 2019
Last Update Posted : September 26, 2019
|Condition or disease||Intervention/treatment||Phase|
|Bladder Cancer||Drug: Durvalumab Biological: S-488210/S-488211||Phase 1 Phase 2|
DURANCE is a registered, phase Ib/II study in patients with surgically debulked bacillus Calmette-Guerin (BCG) unresponsive (resistant or relapsing) non-muscle invasive bladder cancer (NIMBC). Patients will receive up to 24 weeks of durvalumab (a PD-L1 immune checkpoint inhibitor) in combination with S-488210/S-488211 (a 5-peptide cancer vaccine).
Durvalumab will be given as 1500 mg IV infusion every 4 weeks for up to 7 doses, in combination with S-488210/S-S488211 which will be administered as two subcutaneous injections of S-488210/Montanide and S-488211/Montanide starting the day after the first durvalumab dose, then weekly for 6 doses and every 2 weeks for a further 9 doses (up to a maximum of 16 doses).
The phase Ib part of the DURANCE study will look to assess the safety and tolerability of the treatment combination of durvalumab + S-488210/S-488211 by reviewing Dose Limiting Toxicities (DLTs) which have at least a reasonable possibility of being related to the trial treatments (durvalumab and/or S-488210/S-488211). Up to 14 patients will be registered into the phase Ib and provided the DLTs do not exceed the DLT thresholds defined in the trial protocol, the trial will process to the expansion phase of the study (phase 2). In phase 2 the trial will look to assess the disease free survival rate at 1 year following start of treatment.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||64 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase Ib/II Study to Assess the Safety and Activity of DURvalumab (MEDI4736) in Combination With S-488210/S-488211 vAccine in Non-muscle Invasive Bladder CancEr|
|Estimated Study Start Date :||December 2019|
|Estimated Primary Completion Date :||February 2023|
|Estimated Study Completion Date :||February 2027|
Experimental: Durvalumab + S-488210/S-488211
Trial treatment for up to 24 weeks of Durvalumab (1500 mg IV infusion every 4 weeks for up to 7 doses) in combination with S-488210/S-488211 vaccine (given as 2 subcutaneous injections of S-488210/Montanide and S-488211/Montanide starting day after first durvalumab dose, then weekly for the first 6 weeks, and then every 2 weeks for a further 9 doses).
1500 mg IV infusion every 4 weeks for up to 7 doses
Other Name: MEDI 4736
S-488210/S-488211 is given as a 1 mL subcutaneous (SC) injection of S-488210/Montanide emulsion and a 1 mL SC injection of S-488211/Montanide emulsion starting the day after first dose of durvalumab and continuing weekly for 6 doses and then every 2 weeks for a further 9 doses
- Occurrence of Dose Limiting Toxicity (Phase 1b) [ Time Frame: At the end of cycle 1 (cycle 1 is 29 days) ]Detailed adverse event monitoring will be conducted, assessed using CTCAE v5. Dose Limiting Toxicity (DLT) is defined as any adverse event or laboratory abnormality detailed in the trial protocol, that has a reasonable possibility of being related to trial treatment and occurring at anytime during the DLT evaluation period (28 days from the first administration of S-488210/S-488211 on cycle 1 day 2).
- Pathological Disease Free Survival Rate (DFSR) (Phase 2) [ Time Frame: 1 year after start of treatment ]Disease Free Survival will be calculated from start of trial treatment (cycle 1 day 1) until the time at which either primary disease is confirmed to have recurred, any secondary cancer is confirmed or death from any cause. The primary endpoint of Disease Free Survival Rate will be assessed at 1 year from start of treatment (and include patients that start trial treatment and receive combination treatment on cycle 2 day 1) and compared to the historical control rate of 20%.
- 1 year DFSR stratified by HLA-A*02:01 [ Time Frame: 1 year after start of treatment ]If the primary endpoint (DFSR) is statistically signification, comparison of DFSR at 1 year will be conducted between patients that are human leukocyte antigen-A (HLA-A*02:01) positive versus negative.
- 1 year DFSR stratified by PD-L1 status [ Time Frame: 1 year after start of treatment ]DFSR at 1 year stratified by PD-L1 status will be performed.
- 1 year DFSR stratified by baseline Tumour Infiltrating Lymphocyte (TIL) status [ Time Frame: 1 year after start of treatment ]DFSR at 1 year stratified by TIL status (high, intermediate and low) to assess the distribution of a three-category variable (TIL status) over survival status.
- 5 year Overall Survival rate [ Time Frame: 5 years from start of treatment to date of death, if applicable. ]Overall survival will be assessed from time of starting treatment to time of death from any cause.
- Assessment of Quality of Life using EORTC QLQ-C30 questionnaire [ Time Frame: Assessments will be performed at baseline (prior to starting treatment on cycle 1 days 1), every 12 weeks up to 12 months after start of treatment and 24 months after start of treatment. ]Quality of Life assessments will be undertaken using EORTC QLQ-C30 (version 3) questionnaire using Likert score (26 questions scored: 1=not at all, 2=a little, 3=quite a bit, 4=very much; 2 questions scored: 1-7, 1=very poor, 7=excellent) . Descriptions of mean change in EORTC QLQ-C30 scores will be presented and compared to baseline values from pre-treatment.
- Assessment of Quality of Life using EQ-5D-5L questionnaire [ Time Frame: Assessments will be performed at baseline (prior to starting treatment on cycle 1 days 1), every 12 weeks up to 12 months after start of treatment and 24 months after start of treatment. ]Quality of Life assessments will be undertaken using EQ-5D-5L (self-reported) questionnaire using a combination of Likert score (5 questions with 5 dimensions of abilities) and visual analogue score (scored 0-100, 0=worst, 100=best). Descriptions of mean change in EQ-5D-5L scores will be presented and compared to baseline values from pre-treatment.
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): NCT04106115
|Contact: Rubina Begum||020 7679 email@example.com|
|Contact: Marian Duggan||020 7679 firstname.lastname@example.org|
|Principal Investigator:||Mark Linch||University College London Hospital|