SBRT + PD-1 Antibody in Unresectable Locally Recurrent Rectal Cancer（SPARKLE）

NCT06767007 | Recruiting Phase 2 DMC

• 1 other identifier: E2024300
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective study to delve into the therapeutic benefits of combining stereotactic body radiation therapy (SBRT) with PD-1 monoclonal antibody treatment for patients with unresectable locally recurrent rectal cancer (ULRRC). Our aim is to ascertain the safety of this approach and to offer robust, evidence-based medical guidance for the management of ULRRC using this innovative combination therapy. Researchers will combine SBRT with PD-1 for ULRRC to see if this treatment can provide a benefit of survival. Participants will:

1. 1.Receive chemotherapy combined with PD-1 therapy for 1 cycle → SBRT treatment → Chemotherapy combined with PD-1 therapy for 3-6 cycles (assessment 6 weeks after SBRT treatment) → Surgery/Maintenance therapy.
2. 2.Visit the clinic once every 3 months for checkups and tests

Conditions

Unresectable Locally Recurrent Rectal Cancer

Keywords

Unresectable Locally Recurrent Rectal Cancer; Stereotactic Body Radiation Therapy; PD-1 monoclonal antibody

Outcome Measures

Primary Outcomes (1)

• 1 year PFS

  1 year Progression-Free Survival Rate

  1 year

Secondary Outcomes (7)

• 1 year OS

  1 year

• ORR

  1 year

• DCR

  1 year

• R0 resection rate

  1 year

• 2 years PFS

  2 years

Study Arms (1)

SBRT+PD1

EXPERIMENTAL

Participants of experimental arm (SBRT+PD-1 monotherapy group) will receive following treatments by sequences: Chemotherapy combined with PD-1 therapy for 1 cycle → SBRT treatment → Chemotherapy combined with PD-1 therapy for 3-6 cycles (assessment 6 weeks after SBRT treatment) → Surgery/Maintenance therapy.

Radiation: Stereotactic Body Radiation Therapy (SBRT); Drug: PD1; Drug: Chemotherapy

Interventions

Stereotactic Body Radiation Therapy (SBRT) RADIATION

Patients will begin SBRT treatment within 2 weeks after the first round of chemotherapy. Intensity-modulated radiation therapy (IMRT) technology will be used, with a target gross tumor volume (GTV) of 5-8Gy/5 sessions, a total dose of 25-40Gy equivalent to a biological effective dose (BED) of 37.5-72Gy, administered from Monday to Friday. For patients who have previously received pelvic radiotherapy, the re-irradiation dose will be 3-5Gy/5 sessions, a total dose of 15-25Gy equivalent to a BED of 19.5-37.5Gy, administered from Monday to Friday.

SBRT+PD1

PD1 DRUG

The PD-1 monoclonal antibody used is Sintilimab 200mg every 3 weeks

SBRT+PD1

Chemotherapy DRUG

First-line chemotherapy regimen of rectal cancer, using a second-line regimen primarily based on fluorouracil, such as a tri-weekly CAPOX or a bi-weekly mFOLFOX6/FOLFIRI/FOLFOXIRI + targeted therapy

SBRT+PD1

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Before implementing procedures related to the research protocol rather than routine care, informed consent forms with the subject's voluntary signature and dated must be obtained in accordance with regulations and institutional guidelines;
• Patients with pMMR/MSS colorectal cancer;
• Age between 18 and 75 years;
• Tumor recurrence confirmed by histology, cytology, or imaging, and the multidisciplinary team (MDT) including surgeons assesses that the recurrent lesion cannot achieve a one-stage R0 resection (unresectable is defined as: 1. Pelvic MRI showing sacral infiltration at or above S2, 2. And/or lateral pelvic wall invasion, 3. And/or obturator vascular nerve infiltration, 4. After MDT discussion, there are no indications for a one-stage R0 resection, 5. The patient refuses total pelvic exenteration or debulking surgery);
• Locally recurrent rectal adenocarcinoma without clear distant metastasis at diagnosis/MDT team assesses oligometastases as resectable/controllable (UICC 8th edition);
• No prior radiotherapy, or a gap of more than 6 months between the completion of initial radiotherapy and the start of retreatment, with a previous radiotherapy dose of less than 50.4Gy, and no late toxicity in the small bowel or bladder;
• ECOG performance status 0-1;
• Peripheral blood counts and liver and kidney functions within the following allowed ranges (tested within 15 days before treatment start):
• White blood cells (WBC) ≥ 3.0×10\^9/L or Absolute Neutrophil Count (ANC) ≥ 1.5×10\^9/L;
• Hemoglobin (HGB) ≥ 80 g/L;
• Platelets (PLT) ≥ 100×10\^9/L;
• Liver transaminases (AST/ALT) \< 3.0 times the upper limit of the normal range;
• Total bilirubin (TBIL) \< 1.5 times the upper limit of the normal range;
• Creatinine (CREAT) \< 1.5 times the upper limit of the normal range;
• No history of other malignancies, not pregnant or breastfeeding, and should use effective contraception during the study period and for 6 months after the last administration;

You may not qualify if:

• Patients with a history of severe drug allergies (including allergies to platinum-based agents, 5-FU, LV, and 5-HT3 receptor antagonists);
• Patients who have participated in or are currently participating in other clinical trials within 4 weeks of enrollment;
• History of receiving anti-PD-1, PD-L1, PD-L2, CTLA-4, or any other specific T-cell co-stimulation or checkpoint pathway targeted therapies;
• Severe electrolyte abnormalities;
• Presence of gastrointestinal diseases, such as active ulcers of the stomach or duodenum, ulcerative colitis, or unresected tumors with active bleeding; or other conditions that may lead to gastrointestinal bleeding or perforation; or gastrointestinal perforations that have not healed after surgical treatment;
• History of arterial thrombosis or deep vein thrombosis within 6 months; history of bleeding or evidence of bleeding tendency within 2 months;
• Pregnant or breastfeeding women or women who may become pregnant with a positive pregnancy test before the first dose; or female participants who are unwilling to strictly use contraception during the study period and their partners;
• Brain metastases with a diameter greater than 3cm or a total volume greater than 30cc;
• Clinical or radiological evidence of spinal cord compression, or tumors within 3 millimeters of the spinal cord on MRI;
• History or concurrent presence of other active malignant tumors (except for malignant tumors that have been treated curatively and have not recurred for more than 3 years or carcinoma in situ that can be cured with adequate treatment);
• Combined with severe electrocardiogram abnormalities or active coronary artery disease within 12 months before participating in the study, severe/unstable angina or newly diagnosed angina or myocardial infarction, New York Heart Association (NYHA) Class II or higher congestive heart failure;
• Patients with active infections (infections causing fever above 38°C);
• Patients with poorly controlled hypercalcemia, hypertension, diabetes;
• Patients with severe pulmonary diseases (interstitial pneumonia, pulmonary fibrosis, severe emphysema, etc.);
• Patients with mental disorders affecting clinical treatment or a history of central nervous system diseases;

Sponsors & Collaborators

• Sixth Affiliated Hospital, Sun Yat-sen University: lead
• Fudan University: collaborator
• Yunnan Cancer Hospital: collaborator
• Shenzhen People's Hospital: collaborator
• Sun Yat-Sen University Cancer Center: collaborator

Study Sites (1)

Sixth Affiliated Hospital, Sun Yat-sen University

Guangzhou, Guangdong, 510065, China

RECRUITING

MeSH Terms

Interventions

Radiosurgery; Drug Therapy

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Jun Huang, MD

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jun Wang, M.D.

CONTACT

13926451242; huangj97@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Deputy director of the colorectal surgery

Study Record Dates

• First Submitted: January 4, 2025
• First Posted: January 9, 2025
• Study Start: January 6, 2025
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): November 30, 2027
• Last Updated: April 23, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)