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

Study of Adjuvant Durvalumab (MEDI4736) Plus Regorafenib vs Untreated Control in Stage IV Colorectal Cancer Patients With no Evidence of Disease (NED): VIVA Trial

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:

1. R0 resection for surgery,
2. the complete ablation defect covering the lesion on CT scan for radiofrequency,
3. the erogation of ≥ 60 Gy for stereotactic radiotherapy,
4. 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.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer Stage IV; No Evidence of Disease State
• Intervention / Treatment: Drug: Durvalumab Injection for intravenous use 500 mg vial solution for infusion; Drug: Regorafenib 30 mg capsules

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 Type: Interventional
• Enrollment (Anticipated): 182
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Alberto Sobrero, MD; Phone Number: +39 010 555 4386; Email: alberto.sobrero@hsanmartino.it
• Study Contact Backup: Name: Alessandro Pastorino, MD; Phone Number: +39 010 555 4386; Email: alessandro.pastorino@hsanmartino.it

Study Locations

• Italy
  • Liguria
    • Genova, Liguria, Italy, 16132
      • Recruiting
      • IRCCS Ospedale Policlinico San Martino
      • Contact: Alberto Sobrero, MD; Phone Number: +39 010 555 4386; Email: alberto.sobrero@hsanmartino.it
      • Contact: Alessandro Pastorino, MD; Phone Number: +39 010 555 4386; Email: alessandro.pastorino@hsanmartino.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. ≥ 18 years; ECOG PS 0-1;
2. Body weight >30 kg;
3. Histologically confirmed diagnosis of colorectal adenocarcinoma;
4. 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;
5. 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;
6. NED state ascertained by means of CT scan and/or PET scan and/or MRI scan;
7. Life expectancy of at least 12 weeks;
8. CEA within normal limits;
9. No residual toxicity from previous chemotherapy;
10. Adequate organ function;

Exclusion criteria:

1. MSI/dMMR patients;
2. Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia and vitiligo;
3. Active or prior documented autoimmune or inflammatory disorders;
4. Relevant concomitant comorbidities;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	approximately 48 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	approximately 48 months
Overall Survival	Overall survival, defined as the time from the date of randomization to death due to any cause	approximately 48 months
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.	approximately 48 months

Collaborators and Investigators

• Sponsor: Ospedale Policlinico San Martino
• Collaborators: Bayer; Associazione Italiana per la Ricerca sul Cancro; Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente
• Investigators: Principal Investigator: Alberto Sobrero, MD, Ospedale San Martino IRCCS

Study record dates

Study Major Dates

• Study Start (Actual): March 2, 2022
• Primary Completion (Anticipated): March 2, 2024
• Study Completion (Anticipated): March 2, 2024

Study Registration Dates

• First Submitted: May 10, 2022
• First Submitted That Met QC Criteria: May 16, 2022
• First Posted (Actual): May 19, 2022

Study Record Updates

• Last Update Posted (Actual): May 17, 2023
• Last Update Submitted That Met QC Criteria: May 15, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: immunotherapy; adjuvant; tyrosine kinase inhibitors; NED state
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Durvalumab
• Other Study ID Numbers: VIVA TRIAL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No