Targeted Treatment Plus Tislelizumab and HAIC for Advanced CRCLM Failed From Standard Systemic Treatment

NCT06199232 | Active Not Recruiting

• 1 other identifier: SALVLIVE
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief Summary

Hepatic arterial infuison chemothearpy (HAIC), targeted therapy, and programmed death-1 (PD-1) inhibitors have been demonstrated to be effective for colorectal cancer liver metastasis (CRCLM). Thus, the investigators will conduct a prospective trial to explore the efficacy and safety of targeted treatment based on ctDNA genotyping combined with tislelizumab and HAIC as salvage treatment for advanced CRCLM failed from standard systemic treatment, aiming to provide individualized optimized regimen for microsatellite stable (MSS) CRCLM in salvage treatment.

Conditions

ctDNA Genotype; MSS; Failed From Standard Treatment; Liver Metastasis Colon Cancer

Keywords

hepatic arterial infusion chemotherapy; targeted therapy; tislelizumab; ctDNA genotype; MSS CRCLM

Outcome Measures

Primary Outcomes (1)

• PFS rate at 6 months

  Proportion of patients with 6- month progression-free survival after treatment begining in all patients.

  From the date of treatment begining to the date of 6 months after the treatment begining.

Secondary Outcomes (6)

• PFS

  From date of treatment beginning until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

• OS

  From date of treatment beginning until the date of death from any cause, assessed up to 100 months

• intrahepatic PFS

  From date of treatment beginning until the date of first documented progression in liver or date of death from any cause, whichever came first, assessed up to 100 months

• ORR

  Evaluation of tumor burden based on mRECIST criteria through study completion, an average of once per 3 months.

• DCR

  Evaluation of tumor burden based on mRECIST criteria through study completion, an average of once per 3 months.

Study Arms (1)

Treatment Arm

EXPERIMENTAL

HAIC combined with targeted therapy and PD-1 inhibitor

Drug: HAIC+targeted therapy+PD-1 inhibitor

Interventions

HAIC+targeted therapy+PD-1 inhibitor DRUG

HAIC regimen: doublet or triplet regimen based on the response and adverse events occurred in the previous standard treatment (depended on the decision of researchers)-oxaliplatin (85 mg/m2, split into d1 and d2, 0-2h,) and 5-fluorouracial (2g/m2, split into d1 and d2, 2-24h)/ oxaliplatin (65 mg/m2, 0-2h, d1), irinotecan (100 mg/m2, 0-2h, d2), and 5-fluorouracial (2g/m2, split in d1 and d2, 2-24h), repeated every 4 weeks; drug-eluting TACE will be performed at 3rd-4th cycles if the lesions in liver is abundant with blood supply. Tislelizumab (a PD-1 inhibitor): 200 mg, intravenous drip for 30-60 minutes before 24h of HAIC, q4w. Cetuximab (Group A, KRAS/NRAK/BRAF/EGFR wide type and interrupt cetuximab more than 3 months): 500 mg/m2, intravenous drip before HAIC, q4w. Fruquintinib (Group B, KRAS/NRAS/BRAF/EGFR mutation type and wide type but treated with cetuximab in last 3 months): 3 mg/d, d3-23, then suspend for 1w.

Also known as: HAIC+Fruquintinib/Cetuximab+Tislelizumab

Treatment Arm

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years old.
• Colorectal cancer confirmed by histopatology.
• The metastasis is mainly located in liver.
• Unresectable liver metastasis is confirmed by CT/MRI scan and multidisciplinary.
• Failed from standard first- and second-line systemic treatment.
• At least one measurable lesion according to modified Response Evaluation Criteria in Solid Tumors guidelines (mRECIST).
• Eastern Cooperative Oncology Group (ECOG) performance status \<2.
• Child-Pugh A or B (≤ 7).
• Expectant survival time ≥ 3 months.
• Adequate organ function as follows:
• Hemoglobin ≥ 90 g/L;
• Absolute neutrophil count ≥ 1.5×10\^9/L;
• Blood platelet count ≥ 775×10\^9/L;
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤ 5 times of upper limit of normal (ULN);
• Total bilirubin ≤ 2 times of ULN;

You may not qualify if:

• Extensive extrahepatic metastasis (\>25% of tumor burden in liver).
• HER2 (3+) or HER2 amplification.
• MSI-H or dMMR.
• Allergic to contrast media.
• Pregnant or lactational.
• Allergic to oxaliplatin or cetuximab.
• Coinstantaneous a lot of malignant hydrothorax or ascites.
• History of organ transplantation (including bone marrow auto-transplantation and peripheral stem cell transplantation).
• Coinstantaneous infection and need anti-infection therapy.
• Coinstantaneous peripheral nervous system disorder.
• History of obvious mental disorder and central nervous system disorder.
• Concomitant malignancy within 5 years, except for non-melanoma skin cancer and carcinoma in situ of cervix.
• Without legal capacity.
• Impact the study because of medical or ethical reasons.
• Clinically severe gastrointestinal bleeding within 6 months of the start of treatment or any life-threatening bleeding events within 3 months of the start of treatment.

Sponsors & Collaborators

• Peking University: lead

Study Sites (1)

Peking Univerisity Cancer Hospital

Beijing, Beijing Municipality, 100142, China

Location

Related Publications (9)

• Kanas GP, Taylor A, Primrose JN, Langeberg WJ, Kelsh MA, Mowat FS, Alexander DD, Choti MA, Poston G. Survival after liver resection in metastatic colorectal cancer: review and meta-analysis of prognostic factors. Clin Epidemiol. 2012;4:283-301. doi: 10.2147/CLEP.S34285. Epub 2012 Nov 7.

  PMID: 23152705 BACKGROUND

• Hackl C, Neumann P, Gerken M, Loss M, Klinkhammer-Schalke M, Schlitt HJ. Treatment of colorectal liver metastases in Germany: a ten-year population-based analysis of 5772 cases of primary colorectal adenocarcinoma. BMC Cancer. 2014 Nov 4;14:810. doi: 10.1186/1471-2407-14-810.

  PMID: 25369977 BACKGROUND

• Cho M, Gong J, Fakih M. The state of regional therapy in the management of metastatic colorectal cancer to the liver. Expert Rev Anticancer Ther. 2016;16(2):229-45. doi: 10.1586/14737140.2016.1129277. Epub 2016 Jan 13.

  PMID: 26652741 BACKGROUND

• Wang Y, Wei B, Gao J, Cai X, Xu L, Zhong H, Wang B, Sun Y, Guo W, Xu Q, Gu Y. Combination of Fruquintinib and Anti-PD-1 for the Treatment of Colorectal Cancer. J Immunol. 2020 Nov 15;205(10):2905-2915. doi: 10.4049/jimmunol.2000463. Epub 2020 Oct 7.

  PMID: 33028620 BACKGROUND

• Li Q, Cheng X, Zhou C, Tang Y, Li F, Zhang B, Huang T, Wang J, Tu S. Fruquintinib Enhances the Antitumor Immune Responses of Anti-Programmed Death Receptor-1 in Colorectal Cancer. Front Oncol. 2022 Mar 17;12:841977. doi: 10.3389/fonc.2022.841977. eCollection 2022.

  PMID: 35371995 BACKGROUND

• Grothey A, Van Cutsem E, Sobrero A, Siena S, Falcone A, Ychou M, Humblet Y, Bouche O, Mineur L, Barone C, Adenis A, Tabernero J, Yoshino T, Lenz HJ, Goldberg RM, Sargent DJ, Cihon F, Cupit L, Wagner A, Laurent D; CORRECT Study Group. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013 Jan 26;381(9863):303-12. doi: 10.1016/S0140-6736(12)61900-X. Epub 2012 Nov 22.

  PMID: 23177514 RESULT

• Li J, Qin S, Xu R, Yau TC, Ma B, Pan H, Xu J, Bai Y, Chi Y, Wang L, Yeh KH, Bi F, Cheng Y, Le AT, Lin JK, Liu T, Ma D, Kappeler C, Kalmus J, Kim TW; CONCUR Investigators. Regorafenib plus best supportive care versus placebo plus best supportive care in Asian patients with previously treated metastatic colorectal cancer (CONCUR): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2015 Jun;16(6):619-29. doi: 10.1016/S1470-2045(15)70156-7. Epub 2015 May 13.

  PMID: 25981818 RESULT

• Li J, Qin S, Xu RH, Shen L, Xu J, Bai Y, Yang L, Deng Y, Chen ZD, Zhong H, Pan H, Guo W, Shu Y, Yuan Y, Zhou J, Xu N, Liu T, Ma D, Wu C, Cheng Y, Chen D, Li W, Sun S, Yu Z, Cao P, Chen H, Wang J, Wang S, Wang H, Fan S, Hua Y, Su W. Effect of Fruquintinib vs Placebo on Overall Survival in Patients With Previously Treated Metastatic Colorectal Cancer: The FRESCO Randomized Clinical Trial. JAMA. 2018 Jun 26;319(24):2486-2496. doi: 10.1001/jama.2018.7855.

  PMID: 29946728 RESULT

• Mayer RJ, Van Cutsem E, Falcone A, Yoshino T, Garcia-Carbonero R, Mizunuma N, Yamazaki K, Shimada Y, Tabernero J, Komatsu Y, Sobrero A, Boucher E, Peeters M, Tran B, Lenz HJ, Zaniboni A, Hochster H, Cleary JM, Prenen H, Benedetti F, Mizuguchi H, Makris L, Ito M, Ohtsu A; RECOURSE Study Group. Randomized trial of TAS-102 for refractory metastatic colorectal cancer. N Engl J Med. 2015 May 14;372(20):1909-19. doi: 10.1056/NEJMoa1414325.

  PMID: 25970050 RESULT

Study Officials

• Xiaodong Wang, M.D.

  Peking University Cancer Hospital & Institute

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 24, 2023
• First Posted: January 10, 2024
• Study Start: January 23, 2024
• Primary Completion (Estimated): May 23, 2026
• Study Completion (Estimated): May 23, 2027
• Last Updated: January 28, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)