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
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 270
- 试验地点
- 30
- 主要终点
- Clinical complete response (cCR) at 12 months
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
XELOX + DOSTARLIMAB (Arm A)
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)
干预措施: XELOX (Capecitabine and Oxaliplatin) (Drug)
XELOX + DOSTARLIMAB (Arm A)
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)
干预措施: Dostarlimab (Drug)
XELOX (Arm B)
4 cycle- XELOX alone as consolidation treatment
干预措施: XELOX (Capecitabine and Oxaliplatin) (Drug)
结局指标
主要结局
Clinical complete response (cCR) at 12 months
时间窗: After 12 months of the end of the consolidation therapy
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)
次要结局
- 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).)
- Improvement of Quality of Life(Baseline, during treatment, and at the end of adjuvant therapy (approximately 12 months).)
- Adverse Events(From first dose of study treatment through study completion, an average of 3 years)
- Association Between ctDNA Status and Clinical Outcomes(From ctDNA assessment during treatment through follow-up, up to 3 years.)