Short-course Radiotherapy Followed by Sequential Chemotherapy With or Without PD-1 Monoclonal Antibody and Bevacizumab as Total Neoadjuvant Therapy in pMMR/MSS Locally Advanced Rectal Cancer （SPARK）
pMMR/MSS Locally Advanced Rectal Cancer
De qué trata este estudio
El registro indica que este estudio recluta participantes. La disponibilidad puede variar por centro.
- Tipo de estudio
- De intervención
- Fase
- Fase 2
- Rango de edad
- 18 años - 75 años
- Sexo admitido
- Todos los sexos
- Voluntarios sanos
- No aceptados
- Participantes
- 86 Estimado
Estos son puntos de partida, no una decisión de elegibilidad. El equipo debe revisar todos los requisitos.
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Acerca de la investigación
Safety and efficacy of Short-Course Radiotherapy Followed by Sequential Chemotherapy with or without PD-1 Monoclonal Antibody and Bevacizumab as Total Neoadjuvant Therapy in pMMR/MSS Locally Advanced Rectal Cancer.
Complete Response (CR) Rate of Short-Course Radiotherapy Followed by Sequential Chemotherapy with or without PD-1 Monoclonal Antibody and Bevacizumab as Total Neoadjuvant Therapy in pMMR/MSS Locally Advanced Rectal Cancer.
¿Quién podría participar?
La lista siguiente contiene el texto del patrocinador. Puede incluir condiciones, tratamientos previos, resultados de pruebas y otros requisitos. Aparecer en tu búsqueda no significa que califiques.
Inclusion Criteria:
1. Voluntarily signed written informed consent form.
2. Age ≥18 and ≤75 years at enrollment.
3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
4. Life expectancy \>2 years.
5. Histologically confirmed rectal adenocarcinoma.
6. Tumor biopsy demonstrating pMMR (all four mismatch repair proteins-MSH1, MSH2, MSH6, and PMS2-positive by immunohistochemistry) or genetic testing confirming MSS (microsatellite stable).
7. Clinical stage II-III rectal cancer (cT3-4NanyM0 or cTxN+M0) per AJCC 8th Edition TNM staging, assessed via high-resolution MRI ± endoscopic ultrasound/transrectal Doppler ultrasound. Tumor must be ≤12 cm from the anal verge by MRI.
8. Pre-enrollment surgical evaluation by an attending surgeon confirming eligibility for curative-intent R0 resection.
9. No prior systemic or local anti-cancer therapy for rectal cancer (radiotherapy, chemotherapy, immunotherapy, biologics, or small-molecule targeted therapy).
10. Willingness to provide tumor tissue (archival or fresh biopsy) and peripheral blood samples for biomarker analysis during screening and study procedures.
11. Adequate organ function.
12. For women of childbearing potential (WOCBP):Negative urine or serum pregnancy test within 3 days prior to treatment (serum test required if urine result is inconclusive).Agreement to use highly effective contraception (e.g., intrauterine device, hormonal implants) from screening until 120 days after last study treatment. Periodic abstinence and calendar-based methods are prohibited.
13. The subject is willing and able to comply with scheduled visits, treatment regimens, laboratory tests, and other study requirements as outlined in the protocol.
Exclusion Criteria:
1. Suspected metastatic lesions or locally advanced unresectable disease regardless of stage.
2. History of other malignancies within 5 years prior to enrollment, except those cured by local therapy (e.g., basal/squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the breast).
3. Concurrent participation in another interventional clinical trial (observational or non-interventional studies allowed).
4. Acute complications requiring emergency surgery (e.g., bowel obstruction, perforation, hemorrhage).
5. Multiple primary rectal cancers.
6. Prior pelvic/abdominal radiotherapy.
7. Conditions impairing oral drug absorption (e.g., dysphagia, malabsorption syndrome).
8. Prior systemic/local anti-tumor therapy for locally advanced rectal cancer (surgery, chemotherapy, radiotherapy, immunotherapy \[checkpoint inhibitors/agonists, cell therapy\], biologics, or targeted agents).
9. Non-specific immunomodulators (e.g., interleukins, interferons) within 2 weeks or anti-tumor herbal medicines within 1 week prior to treatment.
10. Active autoimmune disease requiring systemic immunosuppression (e.g., corticosteroids \>10 mg/day prednisone equivalent) within 2 years (hormone replacement allowed).
11. History of non-infectious pneumonitis or interstitial lung disease requiring steroids.
12. Bleeding diathesis/coagulopathy or chronic anticoagulation (e.g., CHADS2 score ≥2 for atrial fibrillation).
13. Uncontrolled comorbidities (e.g., decompensated cirrhosis, nephrotic syndrome, peptic ulcers) or psychiatric disorders affecting consent/study compliance.
14. Cardiac history:Myocarditis/cardiomyopathy/malignant arrhythmias.Unstable angina/CHF within 12 months.Arterial thromboembolism within 6 months (e.g., stroke, TIA).Grade ≥3 venous thromboembolism (CTCAE v5.0).Uncontrolled hypertension (SBP ≥160 mmHg/DBP ≥100 mmHg).
15. Active inflammatory bowel disease (Crohn's/ulcerative colitis) or chronic diarrhea.
16Active severe infection requiring hospitalization/systemic antibiotics within 4 weeks (excluding HBV/HCV antivirals).
17.Major surgery/trauma within 30 days or minor procedures within 3 days (excluding PICC placement).
18.Immunodeficiency (HIV-positive, chronic immunosuppressants). 19.Active tuberculosis (confirmed by sputum/X-ray) or syphilis. 20.Prior allogeneic organ/stem cell transplantation. 21.Active hepatitis:HBV: HBsAg+ with HBV-DNA \>1000 copies/mL (200 IU/mL) without antiviral therapy.HCV: Anti-HCV+ with detectable HCV-RNA.
22.Live vaccines within 30 days or planned during study. 23.Hypersensitivity to study drugs/monoclonal antibodies. 24.Substance abuse or psychiatric disorders compromising compliance. 25.Pregnancy/lactation. 26.Conditions confounding efficacy/safety assessments or limiting survival evaluation (e.g., leukemoid reaction \[WBC \>20×10⁹/L\], cachexia \[\>10% weight loss in 3 months\], BMI ≤18).
27.Other conditions deemed inappropriate by investigators.
Entiende la evaluación inicialTratamiento, grupos y participación
El registro puede describir tratamientos y duración sin incluir un calendario completo. Pide al equipo las visitas, procedimientos, riesgos, costos y alternativas. Mantén tu atención habitual salvo que tu médico te indique un cambio.
- Asignación
- Asignación al azar
- Enmascaramiento
- Enmascaramiento simple
Control group
Short-course radiotherapy → CAPOX regimen chemotherapy (6 cycles) → undergo surgery or watch-and-wait strategy within 2-4 weeks after the last dose of capecitabine.
Other: Short-course radiotherapy followed by sequential chemotherapy
Experimental group
Short-course radiotherapy → PD-1 monoclonal antibody and bevacizumab combined with CAPOX regimen chemotherapy (4 cycles) → PD-1 monoclonal antibody combined with CAPOX regimen chemotherapy (2 cycles) → undergo surgery or watch-and-wait strategy within 2-4 weeks after the last dose of capecitabine.
Other: Short-course radiotherapy followed by sequential chemotherapy combined with PD-1 monoclonal antibody and bevacizumab
Short-course radiotherapy followed by sequential chemotherapy combined with PD-1 monoclonal antibody and bevacizumab OTHER
Short-course radiotherapy → PD-1 monoclonal antibody and bevacizumab combined with CAPOX regimen chemotherapy (4 cycles) → PD-1 monoclonal antibody combined with CAPOX regimen chemotherapy (2 cycles) → undergo surgery or watch-and-wait strategy within 2-4 weeks after the last dose of capecitabine.
Short-course radiotherapy followed by sequential chemotherapy OTHER
Short-course radiotherapy → CAPOX regimen chemotherapy (6 cycles) → undergo surgery or watch-and-wait strategy within 2-4 weeks after the last dose of capecitabine.
Qué evalúan los investigadores
Estas medidas indican qué se estudia. No prueban que un tratamiento funcione.
Medidas principales
Complete Response Rate
Plazo: cCR will be assessed 2-4 weeks after completion of TNT, with final clinical classification by 8 weeks after completion of TNT. pCR will be assessed 1 week after TME.
Defined as the proportion of subjects achieving pathological complete response (pCR) or clinical complete response (cCR) following neoadjuvant therapy. pCR is characterized by the absence of residual tumor in the resected primary tumor site and lymph nodes; cCR is defined as achieving ycT0N0 status according to the 2024 CWWD criteria.
Medidas secundarias
Pathological complete response rate
Plazo: 1 week after TME.
Proportion of all randomised participants with no viable tumour in the resected primary tumour and all assessed regional lymph nodes (ypT0N0).
Clinical complete response rate
Plazo: cCR assessed at 2-4 weeks after TNT completion, with final clinical classification by 8 weeks after TNT completion.
Proportion of all randomised participants with confirmed cCR who enter watch-and-wait without total mesorectal excision in the primary-response assessment pathway. Digital rectal examination, contrast-enhanced pelvic MRI and endoscopy must all meet the prespecified cCR criteria.
Tumour regression grade
Plazo: 1 week after TME.
Distribution of primary-tumour regression grades among participants undergoing radical surgery, using the American Joint Committee on Cancer (AJCC) system. Grades 0, 1, 2 and 3 indicate complete, near-complete, partial, and poor or no response, respectively.
R0 resection rate
Plazo: 1 week after TME.
Proportion of participants undergoing radical surgery with no macroscopic residual disease and microscopically negative proximal, distal and circumferential resection margins.
Sphincter preservation rate
Plazo: 1 year after completion of radical treatment. For participants undergoing total mesorectal excision, the surgery date is the reference date.
roportion of all randomised participants managed with watch-and-wait after confirmed cCR or undergoing sphincter-preserving surgery without a permanent stoma. A prophylactic temporary stoma is not a failure. An unreversed stoma determined to be permanent is a failure.
Event-free survival
Plazo: From randomisation to the final follow-up data cut-off, with planned follow-up of at least 36 months per participant. EFS probabilities are assessed at 1, 2 and 3 years.
Time from randomisation to the first objectively confirmed distant metastasis or local disease progression, unresectable disease or macroscopic residual disease at surgery (R2), local recurrence after surgery, or death from any cause.
Title: Overall survival
Plazo: From randomisation to the final follow-up data cut-off, with planned follow-up of at least 36 months per participant. Median OS and the 3-year OS probability are assessed.
Time from randomisation to death from any cause. Participants without a documented death are censored at the last date they were known to be alive.
3-year cumulative incidence of postoperative local recurrence
Plazo: From randomisation through 3 years.
Cumulative incidence of the first objectively confirmed local recurrence after surgery within 3 years after randomisation. Death before local recurrence is treated as a competing event.
3-year cumulative incidence of distant metastasis
Plazo: From randomisation through 3 years.
Cumulative incidence of first objectively confirmed distant metastasis, with death before metastasis treated as a competing event.
Incidence and severity of adverse events
Plazo: AEs: first study treatment to 90 days after the last study-drug dose or 30 days after surgery, whichever is later. Postoperative complications: surgery through day 30.
Incidence and severity of adverse events, including clinically relevant laboratory abnormalities and perioperative events, among participants receiving any protocol treatment, reported by treatment received. Grading uses CTCAE v5.0, except late radiation toxicity, which uses RTOG/EORTC. Postoperative complications are summarised among surgical participants and graded using Clavien-Dindo.
Otras medidas
Health-related quality of life
Plazo: Before first study treatment, 2 days before cycle 4 (21-day cycles), at TNT completion, then every 3 months for 2 years and every 6 months thereafter until study completion, with planned follow-up of at least 36 months after randomisation.
EORTC QLQ-C30 and QLQ-CR29 domain and single-item scores, including changes from baseline.
Patient-reported symptomatic adverse events
Plazo: Every 3 weeks during treatment, starting on the first day of study treatment.
Scores for selected PRO-CTCAE symptom domains and attributes, using the official questionnaire with a 7-day recall period.
Nutritional risk and status
Plazo: Baseline, before each systemic treatment cycle, at TNT completion, and before and 30 days after surgery.
NRS 2002 screening results and scores, together with PG-SGA scores and global categories among participants undergoing that assessment. No PG-SGA score or category is assigned when assessment is not performed after a negative nutritional screen.
Revisa las tablas completas y sus limitaciones en el registro oficial.
Abrir resultados oficiales ↗Centros de investigación (1)
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1 centros
Sixth Affiliated Hospital, Sun Yat-sen UniversityGuangzhou, Guangdong, ChinaReclutando
Equipo y fechas
- Patrocinador principal
- Dechang Diao
- Inicio del estudio
- 23 may 2025 Real
- Finalización primaria
- 31 dic 2031 Estimado
- Finalización del estudio
- 31 dic 2031 Estimado
- Primera publicación
- 5 jun 2025 Real
- Última actualización
- 10 nov 2026 Real
Contactos oficiales del estudio
Título oficial del estudio
Short-Course Radiotherapy Followed by Sequential Chemotherapy Combined With PD-1 Monoclonal Antibody and Bevacizumab Versus Short-Course Radiotherapy Followed by Sequential Chemotherapy as Total Neoadjuvant Therapy in pMMR/MSS Locally Advanced Rectal Cancer
Consulta a Wellness Clinical Research
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Fuente: API v2 de ClinicalTrials.gov. Patrocinadores e investigadores envían la información. La NLM no aprueba la seguridad ni la ciencia de todos los estudios registrados. Aviso del registro.
Consultado: 12 nov 2026 · Última actualización del registro: 10 nov 2026