Locally Advanced Rectal Cancer (LARC)
Conditions
Keywords
dostarlimab, mismatch repair-deficient LARC, real-world, retrospective-prospective study, neoadjuvant setting
Brief summary
This is an observational, retrospective-prospective, multicentre trial enrolling all patients included in the AIFA monitoring registry of Dostarlimab for the indication in rectal cancer. The aims of the study are to describe the clinical outcomes and safety of patients with dMMR/MSI-H locally advanced rectal cancer (LARC) receiving neoadjuvant dostarlimab in the real-world setting.
Detailed description
The primary objective is to describe the activity of neoadjuvant dostarlimab in terms of objective response rate (RECIST 1.1). Secondary objectives are: 1. To describe the activity of neoadjuvant dostarlimab in terms of: * complete clinical response rate at 6 and 12 months * time to clinical complete response * duration of clinical complete response * near-complete clinical response rate at 6 and 12 months * duration of near-complete clinical response * duration of objective response * rate of surgery (total mesorectal excision or local excision) * pathological complete response rate * objective response rate (RECIST 1.1) assessed by central radiological review. 2. To describe the safety of neoadjuvant dostarlimab in terms of: Adverse events/SAE incidence and outcome, time and duration of toxicity according to CTCAE v5.0. 3. To descrive the efficacy of neoadjuvant dostarlimab in terms of: event free-survival (EFS), organ preservation at 3 years, time to ditance recurrence and overall survival (OS)
Interventions
DRUGDostarlimab
Dostarlimab 500 mg iv every 3 weeks for 9 cycles
Sponsors
National Cancer Institute, Naples
Study design
Observational model
COHORT
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed informed consent form * Age \> 18 years * Histologically confirmed stage II-III rectal cancer * dMMR/MSI status assessed locally by Immunohistochemistry, next-generation sequencing or PCR For the retrospective part of the study: * At least one dose of neoadjuvant dostarlimab from November 2023 (i.e. within the period of AIFA dostarlimab monitoring registry activation for the indication in rectal cancer, which is reimbursed according to the Italian law 648/1996, GU n.252 as of 27/10/2023) * Eligible deceased or unreachable patients will also be included to avoid selection biases, in respect of the article 110 bis, paragraph 4 of the Italian Privacy Code (a Data Protection Impact Assessment will be produced and published on the Sponsor website before study initiation, and patients explicitly unwilling before death will be not included). For the prospective part of the study: \- Inclusion in the AIFA dostarlimab monitoring registry for the indication in rectal cancer, to receive dostarlimab according to the Italian law 648/1996, GU n.252 as of 27/10/2023
Exclusion criteria
* \- Distant metastasis * Major cognitive dysfunction or psychiatric disorders * Any previous systemic or local treatment for rectal cancer * Dostarlimab received within an interventional clinical trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | after 3 , 6 and 9 cycles of dostarlimab. Each cycle is 21 days. Up to 6 months | Defined as the percentage of trial participants having a CR or PR, as per RECIST v1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| objective response rate assessed by central radiological review | fter 3 , 6 and 9 cycles of dostarlimab. Each cycle is 21 days. Up to 6 months | defined as the percentage of trial participants having a CR or PR, as per RECIST v1.1. |
| safety of neoadjuvant dostarlimab | at the end of each cycle of dostarlimab (every 21 days ) up to 6 months | Adverse events/Serious adverse events incidence and grading according to NCI-CTCAE v. 5.0 |
| duration of clinical complete response | up to to 12 months | defined as the time from the first documented date of clinical complete response to the date of documented local tumor regrowth, disease recurrence, or last available follow-up, whichever occurs first. |
| near-complete clinical response rate | at 6 and 12 months up to 12 months | absence of mass at digital rectal exam, small mucosal irregularity or superficial ulcer no more than 2 cm in diameter at endoscopic exam, and no metastatic nodes at MRI. |
| pathological complete response rate | after surgery (at 6 months) | defined as a Tumor Regression Grade (TRG) 1 according to Mandard modified scoring system. |
| rate of surgery (total mesorectal excision or local excision) | at 6 months (at the end of neoadjuvant dostarlimab) | defined as the proportion of patients who undergo surgical resection of the primary tumor, including either total mesorectal excision (TME) or local excision |
| Event-free survival | up to 12 months | defined as the time between dostarlimab starting and disease recurrence (local or distant), or disease progression (radiological or clinical) or second primary colorectal malignancy, or death from any cause, whichever comes first. |
| Time to distant recurrence | up to 12 months | defined as the time between dostarlimab starting and distant disease recurrence or progression. Patients who do not have a distant recurrence and are alive at the end of the study will be censored at the date of the last assessment visit. |
| Overall survival | up to 12 months | defined as the time between dostarlimab starting and death from any cause. Patients alive at the end of the study will be censored at the date of the last follow-up contact. |
| duration of near-complete clinical response | up to 12 months | defined as the time from the first documented date of near-complete clinical response to the date of documented conversion to complete clinical response, local tumor regrowth, disease recurrence, or last available follow-up, whichever occurs first. |
Countries
Italy
Contacts
Primary ContactMaria Carmela Piccirillo, MD
Backup ContactPiera Gargiulo, MD
Outcome results
None listed