XELOX Plus DoSTARlimab Versus XELOX Alone as Consolidation Treatment After Standard Chemoradiation in pMMR/MSS or MSI-Low Locally Advanced Rectal Cancer (LARC) Patients

NCT07381777 | Not Yet Recruiting Phase 2

• 1 other identifier: GOIRC-02-2024
• Study Type: interventional
• Target: 270
• Locations: 1 country
• Sites: 30

Brief Summary

This is a phase II, multicenter, randomized (2:1) controlled, clinical trial to evaluate the preliminary efficacy and safety of consolidation chemotherapy (XELOX) plus dostarlimab after standard long-course CRT (ARM A) compared to XELOX alone (ARM B) in patients with pMMR/MSS or MSI-Low LARC (cT3-4 cN0, any cT cN+) candidate to receive standard long course CRT followed by TME. After the surgery, the patients in ARM A will be randomized (1:1) to receive adjuvant dostarlimab (ARM A1) versus follow-up (ARM A2), and in ARM B only follow-up. If clinical complete responses (cCR) are documented after consolidation treatment, the patient may choose not to proceed with surgery and pursue nonoperative management (NOM).

Conditions

Locally Advanced Rectal Cancer (LARC)

Keywords

Consolidation chemotherapy; dostarlimab; pMMR/MSS; MSI-Low; LARC; phase II; clinical complete response (cCR); safety

Outcome Measures

Primary Outcomes (1)

• Clinical complete response (cCR) at 12 months

  To evaluate the clinical complete response (cCR) after 12 months of the end of consolidation treatment, defined as an absence of residual disease on digital and endoscopic rectal examination, as well as the absence of residual disease on rectal MRI, with no restricted diffusion on T2-weighted imaging (cT0N0M0), or the pathological complete response (pCR), in patients who undergo surgery, defined as an absence of viable tumor cells after full pathologic examination of the resected specimen (pT0N0M0)

  After 12 months of the end of the consolidation therapy

Secondary Outcomes (8)

• Clinical complete response (cCR) at 24 and 36 months

  After 24 and 36 months of the end of the consolidation therapy

• Assessment of Organ Preservation Rate

  From the enrollmentat to any time up to 3 years

• Disease Free Survival

  From randomization to recurrence of a tumor up to 3 years

• Overall Survival

  From initiation of study treatment to death from any cause up to 3 years

• Pathological Downstaging Rate

  Perioperative period (at surgical resection).

Study Arms (2)

XELOX + DOSTARLIMAB (Arm A)

EXPERIMENTAL

4 cycle - consolidation chemotherapy (XELOX) plus anti-PD-1 antibody (dostarlimab) after standard long-course CRT, followed by randomisation to adjuvant dostarlimab (Arm A1) versus follow-up (Arm A2)

Drug: XELOX (Capecitabine and Oxaliplatin); Drug: Dostarlimab

XELOX (Arm B)

ACTIVE COMPARATOR

4 cycle- XELOX alone as consolidation treatment

Drug: XELOX (Capecitabine and Oxaliplatin)

Interventions

XELOX (Capecitabine and Oxaliplatin) DRUG

Capecitabine 1000mg/m2 BID + Oxaliplatin 130mg/m2 Q3W

XELOX (Arm B); XELOX + DOSTARLIMAB (Arm A)

Dostarlimab DRUG

Dostarlimab IV 500mg Q3W

XELOX + DOSTARLIMAB (Arm A)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically proven rectal adenocarcinoma with distal extension less 16 cm from the anal verge.
• Stage cT3-4 cN0 cM0, any cT cN+ M0 \[N+ stage, three or more lymph nodes of diameter \>0.5 cm measured by endorectal ultrasound, or one or more lymph nodes of diameter \>1 cm measured by magnetic resonance (MRI)\].
• Proficient mismatch repair (pMMR)/microsatellite stable status (MSS) or microsatellite instability (MSI)-low (MSI-L)
• ECOG-Performance Status 0-1
• No previous treatment with chemotherapy or radiation therapy.
• No prior exposure to immune-mediated therapy, excluding therapeutic anticancer vaccines.
• Neutrophil count \>1,500/mL, platelet count \>100.000/mL, hemoglobin \>9.0 g/dL, serum creatinine \<1.5 3 upper limit of normal (ULN), alanine aminotransferase and aspartate aminotransferase 2.5 3 ULN, total bilirubin \<1.5 3 ULN.
• Signed written informed consent.

You may not qualify if:

• Subjects with active, known, or suspected autoimmune disease requiring systemic treatment (systemic steroids or immunosuppressive agents), except for subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune conditions only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• Distant metastases documented.
• Participants have received a live vaccine within 30 days of the planned start of study therapy. COVID-19 vaccines that do not contain live viruses are allowed. Note: mRNA and adenoviral-based COVID-19 vaccines are considered non-live.
• Participants have a current active history of pneumonitis or interstitial lung disease.

Sponsors & Collaborators

• Gruppo Oncologico Italiano di Ricerca Clinica: lead
• GlaxoSmithKline: collaborator

Study Sites (30)

Ospedale San Donato - UOC Oncologia Medica dell'Aretino, Casentino, Valtiberina, Valdichiana Aretina

Arezzo, Italy

Location

Oncologia medica e prevenzione oncologica - Centro di Riferimento Oncologico

Aviano, Italy

Location

UOC Oncologia Medica IRCCS Azienda Ospedaliero-Universitaria di Bologna

Bologna, Italy

Location

Oncologia Medica Fondazione Poliambulanza Istituto Ospedaliero

Brescia, Italy

Location

UOC Oncologia Medica - ARNAS Garibaldi PO Nesima

Catania, Italy

Location

A.O. Oncologia S. Croce e Carle - presidio Ospedaliero A. Carle

Cuneo, Italy

Location

AOUC Azienda Ospedaliero - Universitaria Careggi Oncologia Medica

Florence, Italy

Location

U.O. Oncologia Medica 1 IRCCS Ospedale Policlinico San Martino

Genova, Italy

Location

S.C. Oncologia Medica, Ospedale Felettino

La Spezia, Italy

Location

IRCCS - Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori"

Meldola (FC), Italy

Location

Oncologia Falck - ASST Grande Ospedale Metropolitano Niguarda

Milan, Italy

Location

Struttura Complessa Oncologia Medica 1 - Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Italy

Location

AOU di Modena - Policlinico di Modena - DH Oncologico

Modena, Italy

Location

Oncologia Clinica Sperimentale Addome Istituto Nazionale Tumori - IRCCS Fondazione G. Pascale

Naples, Italy

Location

UOC Di Oncologia Medica AOU Federico II

Naples, Italy

Location

UOC Oncoematologia AOU Vanvitelli

Naples, Italy

Location

UOC Oncologia 1 - Ospedale Busonera - IRCCS Istituto Oncologico Veneto

Padua, Italy

Location

UOC Oncologia Medica Azienda Ospedaliero Universitaria di Parma

Parma, Italy

Location

SC Oncologia, Fondazione IRCCS Policlinico S. Matteo

Pavia, Italy

Location

Oncologia Medica 2 Universitaria

Pisa, Italy

Location

UOC Oncologia Ravenna Dipartimento di Oncologia ed Ematologia - AUSL Romagna

Ravenna, Italy

Location

SOC di Oncologia Provinciale, AUSL IRCCS di Reggio Emilia

Reggio Emilia, Italy

Location

Fondazione Policlinico Universitario Campus Bio-Medico

Roma, Italy

Location

Oncologia Medica - Policlinico Universitario Gemelli IRCCS

Roma, Italy

Location

IRCCS Istituto clinico humanitas

Rozzano, Italy

Location

Oncologia Ricerca Clinica - IRCCS Casa Sollievo della Sofferenza

San Giovanni Rotondo, Italy

Location

U.O. C. di Oncologia Medica - OSPEDALE CIVILE SS ANNUNZIATA

Sassari, Italy

Location

Oncologia Medica 1, A.O.U. Città della Salute e della Scienza di Torino Ospedale Molinette

Torino, Italy

Location

SOC Oncologia Azienda sanitaria Universitaria Friuli Centrale - P.O. S. Maria della Misericordia

Udine, Italy

Location

ASST Brianza

Vimercate, Italy

Location

MeSH Terms

Interventions

XELOX; Capecitabine; Oxaliplatin; dostarlimab

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Organic Chemicals

Central Study Contacts

Carmine Pinto, MD

CONTACT

+39 0522 96212; Carmine.Pinto@ausl.re.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: randomization (2:1) to consolidation chemotherapy (XELOX) plus anti-PD-1 antibody (dostarlimab) after standard long-course CRT followed by adjuvant dostarlimab VS follow-up (ARM A) compared to XELOX alone as consolidation (ARM B) Arm A subsequent randomization (1:1) to adjuvant dostarlimab for a maximum of 8 cycles (ARM A1) VS only follow-up (ARM A2), and in ARM B only follow-up

Study Record Dates

• First Submitted: March 28, 2025
• First Posted: February 2, 2026
• Study Start: January 31, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): December 31, 2030
• Last Updated: February 2, 2026

Record last verified: 2025-05

Locations

IT (30)