Colorectal Cancer Stage IV, No Evidence of Disease State
Conditions
Keywords
NED state, adjuvant, tyrosine kinase inhibitors, immunotherapy
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.
Interventions
DRUGDurvalumab Injection for intravenous use 500 mg vial solution for infusion
MEDI4736
DRUGRegorafenib 30 mg capsules
BAY73-4506
Sponsors
Associazione Italiana per la Ricerca sul Cancro
Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente
Bayer
Ospedale Policlinico San Martino
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Italy
Contacts
Primary ContactAlberto Sobrero, MD
Backup ContactAlessandro Pastorino, MD
Outcome results
None listed