Clinical trial NCT05382741: Adjuvant Durvalumab Plus Regorafenib vs Untreated Control in Stage IV Colorectal Cancer Patients With no Evidence of Disease (NED): VIVA Trial
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
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Colorectal Cancer Stage IV
No Evidence of Disease State
Keywords: NED state
adjuvant
tyrosine kinase inhibitors
immunotherapy
Lead sponsor: Ospedale Policlinico San Martino
Sponsor class: OTHER
Collaborators: name: Associazione Italiana per la Ricerca sul Cancro
name: Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente
name: Bayer
First posted: 2022-05-19
Enrollment: 182
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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:

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.

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.

Eligibility criteria: 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;

Primary outcomes:
measure: Disease Free Survival
timeFrame: approximately 48 months
Secondary outcomes:
measure: 18 months - Disease Free Survival
timeFrame: approximately 48 months
measure: Overall Survival
timeFrame: approximately 48 months
measure: Incidence of adverse events
timeFrame: approximately 48 months
Other outcomes:
Locations:
city: Genova
country: Italy
facility: IRCCS Ospedale Policlinico San Martino
state: Liguria
Study officials:
affiliation: OSPEDALE SAN MARTINO IRCCS
name: Alberto Sobrero, MD
role: PRINCIPAL_INVESTIGATOR
References: