Combining radiation therapy and PD-1 antibody for liver metastases from colorectal cancer

SBRT Combined With PD-1 Monoclonal Antibody in Unresectable Colorectal Liver Metastases: A Prospective, Multicenter, Single-arm, Phase II Clinical Study (SPARKLE-L)

This study is testing if combining a special type of radiation therapy with a new immune treatment can help people with liver cancer from colorectal cancer feel better and live longer.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Sixth Affiliated Hospital, Sun Yat-sen University (Academic / other)
• Drugs / interventions: chemotherapy, radiation, immunotherapy
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT06794086 on ClinicalTrials.gov

What this trial studies

This study investigates the effectiveness and safety of combining stereotactic body radiation therapy (SBRT) with a PD-1 monoclonal antibody in patients with unresectable liver metastases from colorectal cancer. It is a prospective, open-label, multicenter, single-arm Phase II study where eligible patients will receive SBRT followed by chemotherapy and immunotherapy. The aim is to improve the objective response rate, enhance long-term survival, and improve quality of life for these patients. The study will also assess the efficacy and safety of this combined treatment approach through radiological assessments and biopsies.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with unresectable colorectal cancer liver metastases that are deemed suitable for SBRT.

Not a fit: Patients with resectable liver metastases or those with other significant health issues may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve treatment outcomes and quality of life for patients with unresectable colorectal cancer liver metastases.

How similar studies have performed: While the combination of SBRT and PD-1 inhibitors is a novel approach, similar studies have shown promise in other cancer types, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

1. Written informed consent, voluntarily signed and dated by the subject, must be obtained in accordance with regulatory and institutional guidelines before any procedures related to the study protocol that are not part of routine care are performed.
2. Patients with pMMR/MSS colorectal adenocarcinoma;
3. Age 18-75 years;
4. Patients with histologically or cytologically confirmed colorectal cancer liver metastasis, with or without extrahepatic oligometastatic lesions, who are deemed by the hepatobiliary surgeon within the multidisciplinary team (MDT) to be ineligible for upfront R0 resection of liver metastases (unresectability is defined as one or more of the following conditions: ① Involvement of both left and right branches of the portal vein at the first hepatic hilum; ② Involvement of ≥2 hepatic veins at the second hepatic hilum; ③ No indication for upfront R0 resection/ablation after MDT discussion);
5. Liver metastases are measurable by imaging (based on RECIST 1.1 criteria), with a maximum diameter of ≤6 cm;
6. Patients who have not previously received radiotherapy for liver metastases, or whose liver tissue near the planned irradiation site has not been previously irradiated, and who have at least 700 cc of liver volume outside the treatment area;
7. Previous hepatectomy, systemic chemotherapy, or local ablation therapy, or hepatic arterial infusion pump chemotherapy is allowed, with a washout period of 2 weeks;
8. Child-Pugh score Class A ;
9. ECOG performance status 0-1;
10. Peripheral blood counts and liver and renal function within allowable ranges (tested within 15 days before the start of treatment);
11. No history of other malignancies, not pregnant or breastfeeding, and effective contraception should be used during the study period and for 6 months after the last dose;
12. Life expectancy of ≥6 months.

Exclusion Criteria:

1. Active hepatitis, cirrhosis, or Child-Pugh score Class B or C;
2. Extrahepatic metastases: bone or brain metastases, or ≥3 unresectable lung metastases (according to the 8th edition of the UICC);
3. Unmeasurable liver metastases;
4. History of severe drug allergies (including allergies to platinum agents, 5-FU, LV, and 5-HT3 receptor antagonists);
5. Patients who have participated in or are currently participating in other clinical trials within the past 4 weeks;
6. History of prior treatment with anti-PD-1, PD-L1, PD-L2, CTLA-4, or any other specific T-cell costimulatory or checkpoint pathway-targeted therapies;
7. Severe electrolyte abnormalities;
8. Presence of gastrointestinal diseases, such as active gastric or duodenal ulcers, ulcerative colitis, or unresected tumors with active bleeding; or other conditions that may lead to gastrointestinal bleeding or perforation (Note: Gastrointestinal fistulas that have not healed after surgical treatment, such as rectovesical, rectourethral, or rectovaginal fistulas, are exclusionary unless a stoma has been created and there are no active symptoms);
9. History of arterial thrombosis or deep vein thrombosis within 6 months; history of bleeding or evidence of bleeding tendency within 2 months;
10. Pregnant or breastfeeding women, or women of childbearing potential with a positive pregnancy test before the first dose; or female participants unwilling to strictly practice contraception during the study, as well as their partners;
11. Patients with active autoimmune deficiency diseases requiring systemic treatment within the past 2 years (i.e., use of immunomodulators, corticosteroids, or immunosuppressive drugs);
12. Presence of other active malignancies (except for malignancies that have been treated with curative intent and have been disease-free for over 3 years, or in situ cancers that can be cured with adequate treatment);
13. Presence of severe ECG abnormalities or active coronary artery disease within 12 months before study entry, severe/unstable angina, newly diagnosed angina or myocardial infarction, or New York Heart Association (NYHA) Class II or higher congestive heart failure;
14. Patients with active infections (fever above 38°C due to infection);
15. Patients with poorly controlled hypercalcemia, hypertension, or diabetes;
16. Patients with severe pulmonary diseases (interstitial pneumonia, pulmonary fibrosis, severe emphysema, etc.);
17. Patients with psychiatric disorders affecting clinical management or a history of central nervous system diseases;
18. Patients with severe complications (intestinal obstruction, renal insufficiency, hepatic insufficiency, cerebrovascular disorders, etc.);
19. Presence of any CTCAE Grade 2 or higher toxicity from prior treatments that has not resolved (except for anemia, alopecia, and skin pigmentation);
20. Any unstable medical condition that may affect patient safety or compliance with the study;
21. Patients deemed by the investigator to be unsuitable for participation in this clinical trial.

Where this trial is running

Guangzhou, Guangdong

• Sixth Affiliated Hospital, Sun Yat-sen University — Guangzhou, Guangdong, China (Recruiting)

Study contacts

• Principal investigator: Jun Huang, PhD. — Sun Yat-sen University
• Study coordinator: Jun Huang, PhD.

Conditions Colorectal Cancer; Liver Metastases; Stereotactic body radiation therapy; PD-1 Monoclonal Antibody