Study on the Safety and Efficacy of MR-Linac Technique in Patients With Unresectable Locally Advanced Colon Cancer

Safety and Efficacy Clinical Trial

— UNLACC  

Official title:

Study on the Safety and Efficacy of MR-Linac Technique in Patients With Unresectable Locally Advanced Colon Cancer

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06244537
• Other study ID #: SCCHEC-02-2024-017
• Status: Not yet recruiting
• Phase: N/A
• Start date: February 29, 2024
• Est. completion date: December 31, 2025

Study information

• Verified date: February 2024
• Source: Sichuan Cancer Hospital and Research Institute
• Contact: Qian Peng, chief physician
• Phone: +086 17708130617
• Email: pengqian[@]scszlyy.org.cr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In this phase I single-arm clinical study, 20 patients with T4b unresectable locally advanced colon cancer are proposed to be enrolled, who will be treated with MR-Linac with short course radiotherapy (25Gy/5F), followed by 4 cycles of mFOLFOX6 or 3 cycles of XELOX chemotherapy, then radical surgical resection, and then postoperatively with 8 cycles of mFOLFOX6 or 5 cycles of XELOX. The study will assess patients' surgical R0 resection rate, pCR or cCR rate, PFS, OS, and related adverse effects of treatment, aiming to explore the feasibility, safety, and efficacy of MR-Linac in the treatment of unresectable locally advanced colon cancer.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: December 31, 2025
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

1. Patients over 18 years old

2. Patients can remain in a stationary position on the treatment bed for 1-1.5 hours

3. ECOG score 0-1

4. Pathological diagnosis of colon adenocarcinoma, clinical stage cT4bN0-2M0

5. Organ function is normal, and the following conditions are required: white blood cell count =3.5×10^9/L; platelet count =100×10^9/L; hemoglobin =90g/L. Total bilirubin level =1.5× upper limit of normal (ULN); AST and ALT levels =2.5 × ULN; endogenous creatinine clearance rate: 56-122ml/min; serum creatinine <1.0× ULN; serum albumin =30g/L.

6. Able to adhere to the study protocol during the research period

7. Signed written informed consent

Exclusion Criteria:

1. Patients with dMMR or MSI-H

2. Presence of other types of tumors in addition to colon adenocarcinoma

3. Claustrophobia or inability to undergo MRI or treatment due to the presence of metal implants or other reasons

4. Distant metastasis (M1)

5. Pregnant or lactating women

6. Previous anti-tumor treatment

7. Concurrent use of prohibited drugs for treatment

8. Known history of positive human immunodeficiency virus testing or known acquired immunodeficiency syndrome.

9. Clinically significant (i.e., active) cardiovascular disease: cerebrovascular accident/stroke (<6 months prior to enrollment), myocardial infarction (<6 months prior to enrollment), unstable angina pectoris, congestive heart failure (=New York Heart Association class II) or severe arrhythmia requiring medication treatment

10. Individuals with uncontrolled epilepsy, central nervous system disorders or a history of mental illness, whose clinical severity may hinder signing informed consent or affect patient compliance with oral medication according to the investigator's judgement

11. Organ transplant surgery requiring immunosuppressive therapy

12. Severe, uncontrolled recurrent infections or other severe, uncontrolled comorbidities

Related Conditions & MeSH terms

• Colonic Neoplasms
• Safety and Efficacy

Intervention

Radiation:
• MR-linac
Patients enrolled will be treated with MR-Linac with short course radiotherapy (25Gy/5F), followed by 4 cycles of mFOLFOX6 or 3 cycles of XELOX chemotherapy, then radical surgical resection, and then postoperatively with 8 cycles of mFOLFOX6 or 5 cycles of XELOX chemotherapy.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Sichuan Cancer Hospital and Research Institute

References & Publications (25)

Boldrini L, Intven M, Bassetti M, Valentini V, Gani C. MR-Guided Radiotherapy for Rectal Cancer: Current Perspective on Organ Preservation. Front Oncol. 2021 Mar 30;11:619852. doi: 10.3389/fonc.2021.619852. eCollection 2021. — View Citation

Cao W, Chen HD, Yu YW, Li N, Chen WQ. Changing profiles of cancer burden worldwide and in China: a secondary analysis of the global cancer statistics 2020. Chin Med J (Engl). 2021 Mar 17;134(7):783-791. doi: 10.1097/CM9.0000000000001474. — View Citation

Chang H, Yu X, Xiao WW, Wang QX, Zhou WH, Zeng ZF, Ding PR, Li LR, Gao YH. Neoadjuvant chemoradiotherapy followed by surgery in patients with unresectable locally advanced colon cancer: a prospective observational study. Onco Targets Ther. 2018 Jan 17;11: — View Citation

Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J. Cancer statistics in China, 2015. CA Cancer J Clin. 2016 Mar-Apr;66(2):115-32. doi: 10.3322/caac.21338. Epub 2016 Jan 25. — View Citation

Chiloiro G, Boldrini L, Meldolesi E, Re A, Cellini F, Cusumano D, Corvari B, Mantini G, Balducci M, Valentini V, Gambacorta MA. MR-guided radiotherapy in rectal cancer: First clinical experience of an innovative technology. Clin Transl Radiat Oncol. 2019 — View Citation

Foxtrot Collaborative Group. Feasibility of preoperative chemotherapy for locally advanced, operable colon cancer: the pilot phase of a randomised controlled trial. Lancet Oncol. 2012 Nov;13(11):1152-60. doi: 10.1016/S1470-2045(12)70348-0. Epub 2012 Sep 2 — View Citation

Huang CM, Huang MY, Ma CJ, Yeh Y-, Tsai HL, Huang CW, Huang CJ, Wang JY. Neoadjuvant FOLFOX chemotherapy combined with radiotherapy followed by radical resection in patients with locally advanced colon cancer. Radiat Oncol. 2017 Mar 7;12(1):48. doi: 10.11 — View Citation

Intven MPW, de Mol van Otterloo SR, Mook S, Doornaert PAH, de Groot-van Breugel EN, Sikkes GG, Willemsen-Bosman ME, van Zijp HM, Tijssen RHN. Online adaptive MR-guided radiotherapy for rectal cancer; feasibility of the workflow on a 1.5T MR-linac: clinica — View Citation

Karoui M, Rullier A, Luciani A, Bonnetain F, Auriault ML, Sarran A, Monges G, Trillaud H, Le Malicot K, Leroy K, Sobhani I, Bardier A, Moreau M, Brindel I, Seitz JF, Taieb J. Neoadjuvant FOLFOX 4 versus FOLFOX 4 with Cetuximab versus immediate surgery for — View Citation

Karoui M, Rullier A, Piessen G, Legoux JL, Barbier E, De Chaisemartin C, Lecaille C, Bouche O, Ammarguellat H, Brunetti F, Prudhomme M, Regimbeau JM, Glehen O, Lievre A, Portier G, Hartwig J, Goujon G, Romain B, Lepage C, Taieb J; for PRODIGE 22 investiga — View Citation

Kontaxis C, Bol GH, Kerkmeijer LGW, Lagendijk JJW, Raaymakers BW. Fast online replanning for interfraction rotation correction in prostate radiotherapy. Med Phys. 2017 Oct;44(10):5034-5042. doi: 10.1002/mp.12467. Epub 2017 Aug 9. — View Citation

Krishnamurty DM, Hawkins AT, Wells KO, Mutch MG, Silviera ML, Glasgow SC, Hunt SR, Dharmarajan S. Neoadjuvant Radiation Therapy in Locally Advanced Colon Cancer: a Cohort Analysis. J Gastrointest Surg. 2018 May;22(5):906-912. doi: 10.1007/s11605-018-3676- — View Citation

Qiu B, Ding PR, Cai L, Xiao WW, Zeng ZF, Chen G, Lu ZH, Li LR, Wu XJ, Mirimanoff RO, Pan ZZ, Xu RH, Gao YH. Outcomes of preoperative chemoradiotherapy followed by surgery in patients with unresectable locally advanced sigmoid colon cancer. Chin J Cancer. — View Citation

Reibetanz J, Germer CT. [Neoadjuvant chemotherapy for locally advanced colon cancer : Initial results of the FOxTROT study.]. Chirurg. 2013 Oct 13. doi: 10.1007/s00104-013-2631-8. Online ahead of print. No abstract available. German. — View Citation

Reima H, Soplepmann J, Elme A, Lohmus M, Tiigi R, Uksov D, Innos K. Changes in the quality of care of colorectal cancer in Estonia: a population-based high-resolution study. BMJ Open. 2020 Oct 8;10(10):e035556. doi: 10.1136/bmjopen-2019-035556. — View Citation

Ryan R, Gibbons D, Hyland JM, Treanor D, White A, Mulcahy HE, O'Donoghue DP, Moriarty M, Fennelly D, Sheahan K. Pathological response following long-course neoadjuvant chemoradiotherapy for locally advanced rectal cancer. Histopathology. 2005 Aug;47(2):14 — View Citation

Schmoll HJ, Van Cutsem E, Stein A, Valentini V, Glimelius B, Haustermans K, Nordlinger B, van de Velde CJ, Balmana J, Regula J, Nagtegaal ID, Beets-Tan RG, Arnold D, Ciardiello F, Hoff P, Kerr D, Kohne CH, Labianca R, Price T, Scheithauer W, Sobrero A, Ta — View Citation

Slotman B, Gani C. Online MR-guided radiotherapy - A new era in radiotherapy. Clin Transl Radiat Oncol. 2019 Apr 17;18:102-103. doi: 10.1016/j.ctro.2019.04.011. eCollection 2019 Sep. No abstract available. — View Citation

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caa — View Citation

Tomizawa K, Miura Y, Fukui Y, Hanaoka Y, Toda S, Moriyama J, Inoshita N, Ozaki Y, Takano T, Matoba S, Kuroyanagi H. Curative resection for locally advanced sigmoid colon cancer using neoadjuvant chemotherapy with FOLFOX plus panitumumab: A case report. In — View Citation

van Rossum PS, van Lier AL, van Vulpen M, Reerink O, Lagendijk JJ, Lin SH, van Hillegersberg R, Ruurda JP, Meijer GJ, Lips IM. Diffusion-weighted magnetic resonance imaging for the prediction of pathologic response to neoadjuvant chemoradiotherapy in esop — View Citation

Venigalla S, Chowdhry AK, Wojcieszynski AP, Lukens JN, Plastaras JP, Metz JM, Ben-Josef E, Mahmoud NN, Reiss KA, Shabason JE. Comparative Effectiveness of Neoadjuvant Chemoradiation Versus Upfront Surgery in the Management of Recto-Sigmoid Junction Cancer — View Citation

Winkel D, Bol GH, Kroon PS, van Asselen B, Hackett SS, Werensteijn-Honingh AM, Intven MPW, Eppinga WSC, Tijssen RHN, Kerkmeijer LGW, de Boer HCJ, Mook S, Meijer GJ, Hes J, Willemsen-Bosman M, de Groot-van Breugel EN, Jurgenliemk-Schulz IM, Raaymakers BW. — View Citation

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* Note: There are 25 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MRI-linac Treatment Completion Rate	Is adaptive radiotherapy guided by MRI feasible for patients with locally advanced unresectable colon cancer? The feasibility of each patient will be recorded as a binary variable (1=feasible; 0=not feasible).	2 years
Primary	Clinical complete response (cCR)	Clinical complete response refers to the absence of detectable tumor clinically after treatment.	2 years
Primary	Pathological complete response (pCR)	Pathological complete response is defined as the absence of any signs of cancer in tissue samples after treatment.	2 years
Secondary	Toxicity reaction (CTC 4.0 standard)	CTC 4.0, also known as Common Terminology Criteria for Adverse Events version 4.0, is an extensively used classification system for assessing drug toxicity. This system categorizes drug toxicity into five levels: Grade 0, Grade 1, Grade 2, Grade 3, and Grade 4.	long range
Secondary	R0 resection rate	During surgery, the R0 resection rate refers to the complete removal of the entire tumor with no residual abnormalities present in the surrounding normal tissue.	2 years
Secondary	Surgical complications	Surgical complications refers to adverse events or problems that arise during or after a surgical procedure. These complications can range from minor issues to serious complications that may have significant consequences for the patient.	2 years
Secondary	Local control rate	Proportion of cases in remission and stable disease after treatment, i.e., proportion of patients who did not experience disease progression.	2 years
Secondary	Disease-free survival	The time from the start of treatment to the first tumor recurrence/metastasis, or death of the subject due to any cause.	2 years
Secondary	Overall survival	Time from the start of the patient's treatment to the patient's death from any cause	2 years