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

Официальное название

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

Обзор

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).

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

• Clinical complete response (cCR) at 12 months [Срок оценки: After 12 months of the end of the consolidation therapy]

Вторичные конечные точки (8)

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

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Италия · 30 центров

• 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
• … и ещё 22 центра

Идентификаторы

NCT: NCT07381777 · GOIRC-02-2024

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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