Adjuvant Durvalumab Plus Regorafenib vs Untreated Control in Stage IV Colorectal Cancer Patients With no Evidence of Disease (NED): VIVA Trial

Sponsor

Ospedale Policlinico San Martino (Other)

Overall Status

Recruiting

CT.gov ID

NCT05382741

Collaborator

Associazione Italiana per la Ricerca sul Cancro (Other), Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente (Other)

182

Enrollment

Location

Arms

Anticipated Duration (Months)

7.6

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer Stage IV No Evidence of Disease State	Drug: Durvalumab Injection for intravenous use 500 mg vial solution for infusion Drug: Regorafenib 30 mg capsules	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

182 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Mar 2, 2022

Anticipated Primary Completion Date :

Mar 2, 2024

Anticipated Study Completion Date :

Mar 2, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: DURVALUMAB + REGORAFENIB 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.	Drug: Durvalumab Injection for intravenous use 500 mg vial solution for infusion MEDI4736 Other Names: Imfinzi Drug: Regorafenib 30 mg capsules BAY73-4506 Other Names: Stivarga
No Intervention: CONTROL ARM Observation (follow-up). Crossover to the experimental arm is allowed in case of relapse.

Arm

Intervention/Treatment

Experimental: DURVALUMAB + REGORAFENIB

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.

Drug: Durvalumab Injection for intravenous use 500 mg vial solution for infusion

MEDI4736

Other Names:

Imfinzi

Drug: Regorafenib 30 mg capsules

BAY73-4506

Other Names:

Stivarga

No Intervention: CONTROL ARM

Observation (follow-up). Crossover to the experimental arm is allowed in case of relapse.

Outcome Measures

Primary Outcome Measures

Disease Free Survival [approximately 48 months]
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 [approximately 48 months]
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 [approximately 48 months]
Overall survival, defined as the time from the date of randomization to death due to any cause
Incidence of adverse events [approximately 48 months]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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;