NCT06767007

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

Evaluation of the Efficiency and Safety of Stereotactic Body Radiation Therapy Combined With PD-1 Antibody in the Treatment of Unresectable Locally Recurrent Rectal Cancer: A Prospective, Multicenter, Single-Arm, Open Label, Phase II Study

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 31 (estimated)
• Sponsor: Sixth Affiliated Hospital, Sun Yat-sen University · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

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. 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. Visit the clinic once every 3 months for checkups and tests

Detailed description

This clinical trial is a prospective, open-label, Phase II study. Patients with unresectable locally recurrent rectal cancer(ULRRC) by the multidisciplinary team (MDT) , and where the radiation oncology department within the MDT does not consider the presence of organs at risk (OARs) to affect the execution of SBRT, and who may benefit from improved progression-free survival or the creation of an R0 resection opportunity, are eligible for enrollment. Enrolled patients will receive high-dose fractionated radiotherapy of 5-8Gy per session, for a total of 5 sessions, with chemotherapy based on 5-FU before and after radiotherapy. Imaging assessments for surgical feasibility will be conducted 6 weeks (±2 weeks) after radiotherapy, and the MDT will decide on radical surgery, maintenance chemotherapy, or withdrawal 8 weeks (±2 weeks) after radiotherapy. Participants will receive: 1 cycle of chemotherapy combined with PD-1 therapy → SBRT treatment → 3-6 cycles of chemotherapy combined with PD-1 therapy (assessed 6 weeks after SBRT treatment) → Surgery/Maintenance therapy. Protocol of Stereotactic Body Radiation Therapy (SBRT): 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. Protocol of PD-1 Monoclonal Antibody: The PD-1 monoclonal antibody used is Sintilimab 200mg, administered intravenously on the first day.The study requires completion of at least 4 cycles of PD-1 monotherapy before and after SBRT to be considered eligible. Protocol of Chemotherapy Regimen: The choice of chemotherapy drugs will be at the discretion of the physician, based on the first-line chemotherapy regimen, using a second-line regimen primarily based on fluorouracil, such as a tri-weekly CAPOX or a bi-weekly mFOLFOX6/FOLFIRI/FOLFOXIRI + targeted therapy. Best supportive care will be provided during chemotherapy or chemoradiation. Six weeks (±2 weeks) after the completion of high-dose fractionated radiotherapy, the MDT will assess patients through enhanced CT scans and pelvic MRI to determine disease resectability. If feasible, surgery will be performed 8 weeks (±2 weeks) after chemoradiation. The specific surgical approach depends on the location of recurrence and adjacent structures, as determined by the surgeon. Postoperative adjuvant chemotherapy will be administered based on the assessment by the MDT; if surgery is not possible, maintenance chemotherapy or withdrawal will be considered. Patients who have completed the treatment or those who have not completed the treatment due to intolerable toxic reactions but have not shown tumor progression will be followed up every 3 months. The follow-up will include physical examinations, CT scans (every 3-6 months), pelvic MRI (3 months, 6 months, and the first year after SBRT treatment, then every 6-12 months thereafter), and colonoscopy examinations (once a year during the first, third, and fifth years of treatment). For patients who have already shown tumor progression, telephone follow-ups will be conducted every 3 months until death. During the follow-up, information on subsequent antitumor treatments and survival data of the patients will be collected.

Conditions

• Unresectable Locally Recurrent Rectal Cancer

Interventions

Type	Name	Description
RADIATION	Stereotactic Body Radiation Therapy (SBRT)	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.
DRUG	PD1	The PD-1 monoclonal antibody used is Sintilimab 200mg every 3 weeks
DRUG	Chemotherapy	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

Timeline

• Start date: 2025-01-06
• Primary completion: 2026-11-30
• Completion: 2027-11-30
• First posted: 2025-01-09
• Last updated: 2025-01-22

Locations

1 site across 1 country: China