Back to resultsAdjuvant Durvalumab Plus Regorafenib vs Untreated Control in Stage IV Colorectal Cancer Patients With no Evidence of Disease (NED): VIVA Trial (VIVA)
Primary Purpose
Colorectal Cancer Stage IV, No Evidence of Disease State
Status
Recruiting
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Durvalumab Injection for intravenous use 500 mg vial solution for infusion
Regorafenib 30 mg capsules
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Cancer Stage IV focused on measuring NED state, adjuvant, tyrosine kinase inhibitors, immunotherapy
Eligibility Criteria
Inclusion Criteria:
- ≥ 18 years; ECOG PS 0-1;
- Body weight >30 kg;
- Histologically confirmed diagnosis of colorectal adenocarcinoma;
- Patients must be in NED after completion of any treatments for stage IV CRC, including resections, RFA; RT with or without neoadjuvant/adjuvant therapies or CR after chemotherapy;
- Patients must be randomized within 10 weeks since the achievement of the NED state. Those who have also received adjuvant therapy following the locoregional treatment are still eligible, provided they are randomized within 4 weeks since the last chemotherapy cycle;
- NED state ascertained by means of CT scan and/or PET scan and/or MRI scan;
- Life expectancy of at least 12 weeks;
- CEA within normal limits;
- No residual toxicity from previous chemotherapy;
- Adequate organ function;
Exclusion criteria:
- MSI/dMMR patients;
- Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia and vitiligo;
- Active or prior documented autoimmune or inflammatory disorders;
- Relevant concomitant comorbidities;
Sites / Locations
- IRCCS Ospedale Policlinico San MartinoRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
DURVALUMAB + REGORAFENIB
CONTROL ARM
Arm Description
Durvalumab 1500 mg (120-minute IV infusion) every 28 days, Regorafenib 90 mg/die orally once daily for 21 days in a 28-day cycle. Treatment will be administred up to 1 year.
Observation (follow-up). Crossover to the experimental arm is allowed in case of relapse.
Outcomes
Primary Outcome Measures
Disease Free Survival
Disease free survival, defined as the time from the date of randomization to the earliest documented disease relapse (local or distant), death due to any cause or two consecutive increases of CEA above upper limit (time gap no longer than 30 days).
Secondary Outcome Measures
18 months - Disease Free Survival
Disease free survival, defined as the time from the date of randomization to the earliest documented disease relapse (local or distant), death due to any cause or two consecutive increases of CEA above upper limit (time gap no longer than 30 days).
Overall Survival
Overall survival, defined as the time from the date of randomization to death due to any cause
Incidence of adverse events
An adverse event was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
Toxicity/adverse events are classified according to NCI CTCAE version 5.0.
Full Information
NCT ID
NCT05382741
First Posted
May 10, 2022
Last Updated
May 15, 2023
Sponsor
Ospedale Policlinico San Martino
Collaborators
Associazione Italiana per la Ricerca sul Cancro, Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente, Bayer
1. Study Identification
Unique Protocol Identification Number
NCT05382741
Brief Title
Adjuvant Durvalumab Plus Regorafenib vs Untreated Control in Stage IV Colorectal Cancer Patients With no Evidence of Disease (NED): VIVA Trial
Acronym
VIVA
Official Title
Study of Adjuvant Durvalumab (MEDI4736) Plus Regorafenib vs Untreated Control in Stage IV Colorectal Cancer Patients With no Evidence of Disease (NED): VIVA Trial
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 2, 2022 (Actual)
Primary Completion Date
March 2, 2024 (Anticipated)
Study Completion Date
March 2, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ospedale Policlinico San Martino
Collaborators
Associazione Italiana per la Ricerca sul Cancro, Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente, Bayer
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to evaluate the efficacy of Durvalumab plus Regorafenib versus observation for patients with stage IV colorectal cancer achieving the no evidence of disease state.
The NED state can be achieved in any line of treatment and it is defined as:
R0 resection for surgery,
the complete ablation defect covering the lesion on CT scan for radiofrequency,
the erogation of ≥ 60 Gy for stereotactic radiotherapy,
complete response to antineoplastic treatments on CT scan. In all these cases CEA and CA 19.9 must be within normal limits at the time of randomization.
Participants in this study will receive:
Experimental arm:
Regorafenib 90 mg d1-21 every 28 days plus Durvalumab 1500 mg every 28 days for 1 year
Control arm:
Observation (crossover to Experimental arm is allowed in case of relapse)
Tumor assessment will be performed every 12 weeks.
Detailed Description
The safety run-in phase is planned for the first 4 patients randomized to the experimental arm using a starting dose of 60 mg/die of Regorafenib (and fixed 1500 mg of Durvalumab), to be escalated after 2 months to 90 mg/die if < 2 patients report serious adverse events.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer Stage IV, No Evidence of Disease State
Keywords
NED state, adjuvant, tyrosine kinase inhibitors, immunotherapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
182 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
DURVALUMAB + REGORAFENIB
Arm Type
Experimental
Arm Description
Durvalumab 1500 mg (120-minute IV infusion) every 28 days, Regorafenib 90 mg/die orally once daily for 21 days in a 28-day cycle.
Treatment will be administred up to 1 year.
Arm Title
CONTROL ARM
Arm Type
No Intervention
Arm Description
Observation (follow-up).
Crossover to the experimental arm is allowed in case of relapse.
Intervention Type
Drug
Intervention Name(s)
Durvalumab Injection for intravenous use 500 mg vial solution for infusion
Other Intervention Name(s)
Imfinzi
Intervention Description
MEDI4736
Intervention Type
Drug
Intervention Name(s)
Regorafenib 30 mg capsules
Other Intervention Name(s)
Stivarga
Intervention Description
BAY73-4506
Primary Outcome Measure Information:
Title
Disease Free Survival
Description
Disease free survival, defined as the time from the date of randomization to the earliest documented disease relapse (local or distant), death due to any cause or two consecutive increases of CEA above upper limit (time gap no longer than 30 days).
Time Frame
approximately 48 months
Secondary Outcome Measure Information:
Title
18 months - Disease Free Survival
Description
Disease free survival, defined as the time from the date of randomization to the earliest documented disease relapse (local or distant), death due to any cause or two consecutive increases of CEA above upper limit (time gap no longer than 30 days).
Time Frame
approximately 48 months
Title
Overall Survival
Description
Overall survival, defined as the time from the date of randomization to death due to any cause
Time Frame
approximately 48 months
Title
Incidence of adverse events
Description
An adverse event was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
Toxicity/adverse events are classified according to NCI CTCAE version 5.0.
Time Frame
approximately 48 months
10. Eligibility
Sex
All
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
≥ 18 years; ECOG PS 0-1;
Body weight >30 kg;
Histologically confirmed diagnosis of colorectal adenocarcinoma;
Patients must be in NED after completion of any treatments for stage IV CRC, including resections, RFA; RT with or without neoadjuvant/adjuvant therapies or CR after chemotherapy;
Patients must be randomized within 10 weeks since the achievement of the NED state. Those who have also received adjuvant therapy following the locoregional treatment are still eligible, provided they are randomized within 4 weeks since the last chemotherapy cycle;
NED state ascertained by means of CT scan and/or PET scan and/or MRI scan;
Life expectancy of at least 12 weeks;
CEA within normal limits;
No residual toxicity from previous chemotherapy;
Adequate organ function;
Exclusion criteria:
MSI/dMMR patients;
Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia and vitiligo;
Active or prior documented autoimmune or inflammatory disorders;
Relevant concomitant comorbidities;
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Alberto Sobrero, MD
Phone
+39 010 555 4386
Email
alberto.sobrero@hsanmartino.it
First Name & Middle Initial & Last Name or Official Title & Degree
Alessandro Pastorino, MD
Phone
+39 010 555 4386
Email
alessandro.pastorino@hsanmartino.it
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alberto Sobrero, MD
Organizational Affiliation
OSPEDALE SAN MARTINO IRCCS
Official's Role
Principal Investigator
Facility Information:
Facility Name
IRCCS Ospedale Policlinico San Martino
City
Genova
State/Province
Liguria
ZIP/Postal Code
16132
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alberto Sobrero, MD
Phone
+39 010 555 4386
Email
alberto.sobrero@hsanmartino.it
First Name & Middle Initial & Last Name & Degree
Alessandro Pastorino, MD
Phone
+39 010 555 4386
Email
alessandro.pastorino@hsanmartino.it
12. IPD Sharing Statement
Learn more about this trial
Adjuvant Durvalumab Plus Regorafenib vs Untreated Control in Stage IV Colorectal Cancer Patients With no Evidence of Disease (NED): VIVA Trial
We'll reach out to this number within 24 hrs