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Not yet recruiting NCT07381777

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

Phase II Interventional Locally Advanced Rectal Cancer (LARC)

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: XELOX (Capecitabine and Oxaliplatin), Dostarlimab.
Who it may be relevant to
Registry conditions: Locally Advanced Rectal Cancer (LARC). Basic parameters: No limits · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
Italy
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

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Official title

Phase II Randomized Trial of XELOX Plus DoSTARlimab Versus XELOX Alone as Consolidation Treatment After Standard Chemoradiation in pMMR/MSS or MSI-Low Locally Advanced Rectal Cancer (LARC) Patients - IMMUNOSTAR Trial GOIRC-02-2024

Overview

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).

Detailed description

This is a phase II, multicenter, randomized (2:1) controlled, clinical trial to evaluate the preliminary efficacy and safety of consolidation chemotherapy (XELOX) plus anti-PD-1 antibody (dostarlimab) after standard long-course CRT followed by adjuvant dostarlimab versus follow-up (ARM A) compared to XELOX alone as consolidation (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.

Subsequent randomization into a ratio 1:1 will be performed after surgery, only for patients randomized in ARM A, to receive adjuvant dostarlimab for a maximum of 8 cycles (ARM A1) versus only follow-up (ARM A2), and in ARM B only follow-up (Figure 1).

If clinical complete responses (cCR) are documented after restaging, the patient may choose not to proceed with surgery and pursue nonoperative management (NOM) (Figure 1).

The patients before randomization will be stratified as follows:

* cT4 or \< cT4 stage; * positive or negative lymph nodes.

Interventions

  • Drug XELOX (Capecitabine and Oxaliplatin)
    Capecitabine 1000mg/m2 BID + Oxaliplatin 130mg/m2 Q3W
  • Drug Dostarlimab
    Dostarlimab IV 500mg Q3W

Primary outcome measures

  • Clinical complete response (cCR) at 12 months [Time frame: After 12 months of the end of the consolidation therapy]
Secondary outcome measures (8)
  • Clinical complete response (cCR) at 24 and 36 months [Time frame: After 24 and 36 months of the end of the consolidation therapy]
  • Assessment of Organ Preservation Rate [Time frame: From the enrollmentat to any time up to 3 years]
  • Disease Free Survival [Time frame: From randomization to recurrence of a tumor up to 3 years]
  • Overall Survival [Time frame: From initiation of study treatment to death from any cause up to 3 years]
  • Pathological Downstaging Rate [Time frame: Perioperative period (at surgical resection).]
  • Improvement of Quality of Life [Time frame: Baseline, during treatment, and at the end of adjuvant therapy (approximately 12 months).]
  • Adverse Events [Time frame: From first dose of study treatment through study completion, an average of 3 years]
  • Association Between ctDNA Status and Clinical Outcomes [Time frame: From ctDNA assessment during treatment through follow-up, up to 3 years.]

Eligibility criteria

Inclusion criteria

  • 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.

Exclusion criteria

  • 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Randomized
Model
Parallel assignment
Masking
Open label
Primary purpose
Treatment

Study locations

Italy · 30 centers
  • Ospedale San Donato - UOC Oncologia Medica dell'Aretino, Casentino, Valtiberina, Valdichia — Arezzo
  • Oncologia medica e prevenzione oncologica - Centro di Riferimento Oncologico — Aviano
  • UOC Oncologia Medica IRCCS Azienda Ospedaliero-Universitaria di Bologna — Bologna
  • Oncologia Medica Fondazione Poliambulanza Istituto Ospedaliero — Brescia
  • UOC Oncologia Medica - ARNAS Garibaldi PO Nesima — Catania
  • A.O. Oncologia S. Croce e Carle - presidio Ospedaliero A. Carle — Cuneo
  • AOUC Azienda Ospedaliero - Universitaria Careggi Oncologia Medica — Florence
  • U.O. Oncologia Medica 1 IRCCS Ospedale Policlinico San Martino — Genova
  • … and 22 more centers

Identifiers

NCT: NCT07381777 · GOIRC-02-2024

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗