Ignite Creation Date:
2024-05-06 @ 3:20 PM
Last Modification Date:
2024-10-26 @ 1:47 PM
Study NCT ID:
NCT04602078
Status:
COMPLETED
Last Update Posted:
2024-03-21
First Post:
2020-10-06
Brief Title:
Study of Atezolizumab Combined With Split-dose Gemcitabine Plus Cisplatin in Urothelial Carcinoma
Sponsor:
Spanish Oncology Genito-Urinary Group
Organization:
Spanish Oncology Genito-Urinary Group
Study Overview
Official Title:
Phase II Multicenter Non-randomized Single-arm Open-label Trial of Atezolizumab in Combination of Split-doses of Gemcitabine Plus Cisplatin in Patients With Locally Advanced or Metastatic Urothelial Carcinoma
Status:
COMPLETED
Status Verified Date:
2023-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
AUREA
Brief Summary:
Phase II multicenter non-randomized single-arm open-label trial of atezolizumab in combination of split-doses of gemcitabine plus cisplatin in patients with locally advanced or metastatic urothelial carcinoma
The Aurea trial aims to evaluate the preliminary efficacy of atezolizumab plus split-dose gemcitabine and cisplatin GC for the first-line setting in patients with histologically confirmed advanced locally advanced and metastatic urothelial cancer in terms of overall response rate ORR assessed by the investigator using the Response Evaluation Criteria in Solid Tumors RECIST v11
Secondary objectives include efficacy clinical benefit rate duration of response time to response overall survival and progression-free survival safety frequency and severity of adverse events assessed by NCI CTCAE v50 and exploratory endpoints correlation of prognostic biomarkersfactors with efficacy and relationship between the expression of PD-L1 and microbiome with ORR and PFS
At least 66 patients will be included
The treatment schedule is as follows
Atezolizumab at a fixed dose of 1200 mgm2 by intravenous IV infusion on D1 of each 21-day cycle up to disease progression unacceptable toxicity or absence of clinical benefit
Gemcitabine 1000 mgm2 IV on D1 and 1000 mgm2 IV on D8 of each 21-day cycle plus Cisplatin 70 mgm2 by IV on split-dose schedule of 35 mgm2 on day 1 D1 and 35 mgm2 on day 8 D8 for up to 6 cycles
The Aurea trial aims to evaluate the preliminary efficacy of atezolizumab plus split-dose gemcitabine and cisplatin GC for the first-line setting in patients with histologically confirmed advanced locally advanced and metastatic urothelial cancer in terms of overall response rate ORR assessed by the investigator using the Response Evaluation Criteria in Solid Tumors RECIST v11
Secondary objectives include efficacy clinical benefit rate duration of response time to response overall survival and progression-free survival safety frequency and severity of adverse events assessed by NCI CTCAE v50 and exploratory endpoints correlation of prognostic biomarkersfactors with efficacy and relationship between the expression of PD-L1 and microbiome with ORR and PFS
At least 66 patients will be included
The treatment schedule is as follows
Atezolizumab at a fixed dose of 1200 mgm2 by intravenous IV infusion on D1 of each 21-day cycle up to disease progression unacceptable toxicity or absence of clinical benefit
Gemcitabine 1000 mgm2 IV on D1 and 1000 mgm2 IV on D8 of each 21-day cycle plus Cisplatin 70 mgm2 by IV on split-dose schedule of 35 mgm2 on day 1 D1 and 35 mgm2 on day 8 D8 for up to 6 cycles
Detailed Description:
The results of trials combining checkpoint inhibitors or platinum-based chemotherapy plus PD-1PD-L1 inhibitors are eagerly awaited The combination of split cisplatin with atezolizumab is a feasible treatment that may provide better outcomes than carboplatinbased combinations
In the IMvigor130 52 of patients considered cisplatin eligible at the entry of the study were treated with carboplatin Subanalysis presented at European Society of Medical Oncology ESMO 2019 Grande E et al 2019 has also shown a longer median OS are achieved with cisplatin-based chemotherapy combined with atezolizumab 217 months when compared to the carboplatin-based chemotherapy plus atezolizumab 142 months with similar findings when it comes to PFS 88 months with cisplatingemcitabineatezolizumab vs 71 months carboplatingemcitabineatezolizumab
A reasonable strategy may be the use of split cisplatin with atezolizumab to increase the number of patients receiving cisplatin
The AUREA study is a multicenter open labelled single arm multicohort Phase II clinical trial of of atezolizumab in combination of split-dose cisplatin plus gemcitabine in patients with locally advanced or metastatic urothelial carcinoma additional details on the eligibility criteria of the study are found in section 6 of this protocol
The design includes screening phase combined treatment initial phase monotherapy treatment phase follow-up phase and translational research with biopsies blood samples and faecal samples
The dose scheme includes the initial dose of atezolizumab 1200 mg intravenously administered every 21 days one cycle up to disease progression unacceptable toxicity or absence of clinical benefit Dose adjustment or dose reductions of atezolizumab are not expected AUREA is an Investigator Initiated Study the Sponsor will supply Atezolizumab for up to 24 months of treatment for each patient For those patients in which the PI considers that the best option for the patient is continuing atezolizumab for more than 24 months available commercial Site supplies should be used after managed local administrative regulation Gemcitabine 1000 mgm2 IV on D1 and 1000 mgm2 IV on D8 of each 21-day cycle plus Cisplatin 70 mgm2 by IV on split-dose schedule of 35 mgm2 on day 1 D1 and 35 mgm2 on day 8 D8 for up to 6 cycles
Study treatment will begin as soon as possible after signing the informed consent Before each treatment administration chemotherapyatezolizumab administration laboratory medical consulting and other determinations will be performed to ensure that treatment can be safely administered
A CT Scan or MRI will be performed at baseline on week 9 week 18 and then every 12 weeks q12w 1w until objective disease progression as per PIs criteria or death whichever comes first Blood samples for biomarkers studies should be collected before administration of cycle 4 and at the time of Progression Disease PD end of treatment if applicable
For patients with progression reported as per RECIST criteria at week 9 continuity of treatment with atezolizumab should be evaluated by the PI of each site as per clinical benefit criteria
In the IMvigor130 52 of patients considered cisplatin eligible at the entry of the study were treated with carboplatin Subanalysis presented at European Society of Medical Oncology ESMO 2019 Grande E et al 2019 has also shown a longer median OS are achieved with cisplatin-based chemotherapy combined with atezolizumab 217 months when compared to the carboplatin-based chemotherapy plus atezolizumab 142 months with similar findings when it comes to PFS 88 months with cisplatingemcitabineatezolizumab vs 71 months carboplatingemcitabineatezolizumab
A reasonable strategy may be the use of split cisplatin with atezolizumab to increase the number of patients receiving cisplatin
The AUREA study is a multicenter open labelled single arm multicohort Phase II clinical trial of of atezolizumab in combination of split-dose cisplatin plus gemcitabine in patients with locally advanced or metastatic urothelial carcinoma additional details on the eligibility criteria of the study are found in section 6 of this protocol
The design includes screening phase combined treatment initial phase monotherapy treatment phase follow-up phase and translational research with biopsies blood samples and faecal samples
The dose scheme includes the initial dose of atezolizumab 1200 mg intravenously administered every 21 days one cycle up to disease progression unacceptable toxicity or absence of clinical benefit Dose adjustment or dose reductions of atezolizumab are not expected AUREA is an Investigator Initiated Study the Sponsor will supply Atezolizumab for up to 24 months of treatment for each patient For those patients in which the PI considers that the best option for the patient is continuing atezolizumab for more than 24 months available commercial Site supplies should be used after managed local administrative regulation Gemcitabine 1000 mgm2 IV on D1 and 1000 mgm2 IV on D8 of each 21-day cycle plus Cisplatin 70 mgm2 by IV on split-dose schedule of 35 mgm2 on day 1 D1 and 35 mgm2 on day 8 D8 for up to 6 cycles
Study treatment will begin as soon as possible after signing the informed consent Before each treatment administration chemotherapyatezolizumab administration laboratory medical consulting and other determinations will be performed to ensure that treatment can be safely administered
A CT Scan or MRI will be performed at baseline on week 9 week 18 and then every 12 weeks q12w 1w until objective disease progression as per PIs criteria or death whichever comes first Blood samples for biomarkers studies should be collected before administration of cycle 4 and at the time of Progression Disease PD end of treatment if applicable
For patients with progression reported as per RECIST criteria at week 9 continuity of treatment with atezolizumab should be evaluated by the PI of each site as per clinical benefit criteria
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2020-001326-65 | EUDRACT_NUMBER | None | None |