Immunotherapy Combined With Carbon Ion Radiotherapy for Locally Advanced Cervical Cancer

NCT07702838 | Recruiting DMC

• 1 other identifier: IRB-2026-877（IIT）
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This study explores the therapeutic effect of carbon ion radiotherapy plus immunotherapy and chemotherapy for locally advanced cervical cancer.

Conditions

Uterine Cervical Neoplasms

Keywords

Carbon Ion Radiotherapy; Immunotherapy; Chemotherapy; Survival Outcome; Uterine Cervical Neoplasms

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  This endpoint is determined based on investigators' assessments per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1). If disease progression cannot be confirmed by imaging according to RECIST 1.1, progressive disease (PD) histopathologically verified following carbon ion radiotherapy combined with three-dimensional brachytherapy, concurrent chemotherapy and immunotherapy shall serve as the criterion for progression determination.

  At 2 years after the start of trial treatment

Secondary Outcomes (2)

• Overall survival (OS)

  At 2 years after the start of trial treatment

• Acute and late toxicities

  Acute toxicities: AEs within 90 days of carbon ion radiotherapy start, graded per CTCAE & RTOG acute radiation morbidity criteria. Late toxicities: Radiation-associated tissue injuries new or worsening >90 days after the star radiotherapy initiation.

Study Arms (1)

Immunotherapy Combined with Carbon Ion Radiotherapy and Concurrent Chemotherapy for Locally Advanced

EXPERIMENTAL

Immunotherapy: Anti-PD-1 therapy administered once every 3 weeks starting at radiotherapy initiation, with a total maintenance duration of 2 years. Chemotherapy: Weekly concurrent single-agent cisplatin (dose: 40 mg/m² per week) or carboplatin (target AUC = 2) given simultaneously with carbon ion external beam radiotherapy, for a total of 4 cycles. Radiotherapy: Carbon ion external beam radiotherapy plus 3 courses of three-dimensional intracavitary brachytherapy.

Radiation: Carbon ion external beam radiotherapy plus 3 courses of three-dimensional brachytherapy.

Interventions

Carbon ion external beam radiotherapy plus 3 courses of three-dimensional brachytherapy. RADIATION

Immunotherapy: Anti-PD-1 therapy administered once every 3 weeks starting at radiotherapy initiation, with a total maintenance duration of 2 years. Chemotherapy: Weekly concurrent single-agent cisplatin (dose: 40 mg/m² per week) or carboplatin (target AUC = 2) is given simultaneously with carbon ion external beam radiotherapy for a total of 4 cycles.

Also known as: Immunotherapy: Anti-PD-1 therapy, Chemotherapy

Immunotherapy Combined with Carbon Ion Radiotherapy and Concurrent Chemotherapy for Locally Advanced

Eligibility Criteria

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

You may qualify if:

• Female patients aged ≥ 18 years at the time of signing the informed consent form.
• Histopathologically confirmed diagnosis of cervical cancer (squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinoma).
• Stage IIB-IVA disease per the 2018 FIGO staging system.
• Presence of measurable lesions as defined by RECIST version 1.1.
• Patients reviewed by the carbon ion radiotherapy multidisciplinary team (MDT) with an indication for carbon ion radiotherapy.
• Patients voluntarily receiving carbon ion radiotherapy at Zhejiang Cancer Hospital and bearing all relevant treatment expenses.
• Complete clinical and imaging data available.
• Patients willing to participate in the trial and complete questionnaire surveys.
• Patients willing to participate in the trial and provide biospecimens, including cervical tissue, various body fluid specimens and tissue samples.
• Patients willing to attend regular standardised outpatient follow-up visits at our hospital.
• Eastern Cooperative 11. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0-2.
• No prior history of surgery, radiotherapy or chemotherapy for cervical cancer.
• Adequate function of major vital organs (bone marrow, liver, kidney, etc.), with laboratory values meeting the following criteria within 1 week prior to treatment: Absolute neutrophil count (ANC) ≥ 1500/μL; Platelet count ≥ 100,000/μL; Haemoglobin ≥ 9.0 g/dL (or ≥ 5.6 mmol/L); Creatinine clearance ≥ 50 mL/min; Total bilirubin ≤ 1.5 × upper limit of normal (ULN); if total bilirubin \> 1.5 × ULN, direct bilirubin shall be ≤ ULN; Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN; International Normalised Ratio (INR), prothrombin time (PT), and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN (excluding patients receiving anticoagulant therapy within the therapeutic range).
• Estimated overall survival ≥ 6 months.

You may not qualify if:

• Presence of severe concomitant complications (e.g., uncontrolled cardiovascular disease, hypertension, diabetes mellitus, refractory infection, active peptic ulcer, uncontrolled psychiatric disorders, etc.)
• Concurrent active second primary malignancy.
• Tumour invasion of the rectum (Stage IVA) or peritoneal metastasis (M1).
• Prior receipt of immunotherapy agents (including anti-PD-1, anti-PD-L1, anti-CTLA-4, etc.).
• Prior radical surgery, radiotherapy, or systemic therapy (including investigational agents) for cervical cancer. Note: Conisation of the cervix is permitted.
• Administration of any investigational drug within 4 weeks before the initiation of immunotherapy.
• Confirmed immunodeficiency or receipt of chronic systemic corticosteroid therapy (prednisone equivalent dose \>10 mg/day) or other immunosuppressive therapy within 7 days prior to immunotherapy.
• History of grade ≥3 severe hypersensitivity reactions to immunotherapeutic agents.
• Active autoimmune disease requiring systemic therapy within the past 2 years (replacement therapies such as thyroxine, insulin and physiological glucocorticoids are excluded).
• Prior history of non-infectious pneumonitis/interstitial lung disease requiring steroid treatment, or current active pneumonitis/interstitial lung disease.
• Active infection requiring systemic treatment.
• History of active hepatitis B (HBsAg positive) or active hepatitis C (detectable HCV RNA).
• Any disease, treatment, laboratory abnormality or other condition that, in the investigator's judgement, may confound study results, hinder full study participation or pose additional risks to the subject.
• Known psychiatric illness or substance abuse that may impair subject compliance; pregnant or breastfeeding females, or those planning conception/pregnancy during the study period (from screening to 120 days after the last study treatment).
• Previous allogeneic tissue or solid organ transplantation.

Sponsors & Collaborators

• Zhejiang Cancer Hospital: lead

Study Sites (1)

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310022, China

RECRUITING

Related Publications (24)

• Azzam AY, Ghozy S, Kallmes KM, Adusumilli G, Heit JJ, Hassan AE, Kadirvel R, Kallmes DF. Aspiration thrombectomy versus stent retriever thrombectomy alone for acute ischemic stroke: evaluating the overlapping meta-analyses. J Neurointerv Surg. 2023 Jan;15(1):34-38. doi: 10.1136/neurintsurg-2022-018849. Epub 2022 May 18.

  PMID: 35584912 BACKGROUND

• Wakatsuki M, Kato S, Kiyohara H, Ohno T, Karasawa K, Tamaki T, Ando K, Tsujii H, Nakano T, Kamada T, Shozu M; Working Group of the Gynecological Tumor. Clinical trial of prophylactic extended-field carbon-ion radiotherapy for locally advanced uterine cervical cancer (protocol 0508). PLoS One. 2015 May 20;10(5):e0127587. doi: 10.1371/journal.pone.0127587. eCollection 2015.

  PMID: 25993047 BACKGROUND

• Wakatsuki M, Kato S, Ohno T, Karasawa K, Ando K, Kiyohara H, Tsujii H, Nakano T, Kamada T, Shozu M; Working Group of the Gynecological Tumor. Dose-escalation study of carbon ion radiotherapy for locally advanced squamous cell carcinoma of the uterine cervix (9902). Gynecol Oncol. 2014 Jan;132(1):87-92. doi: 10.1016/j.ygyno.2013.10.021. Epub 2013 Oct 29.

  PMID: 24183732 BACKGROUND

• Jahangir Z, Bakillah A, Iqbal J. Regulation of Sphingolipid Metabolism by MicroRNAs: A Potential Approach to Alleviate Atherosclerosis. Diseases. 2018 Sep 17;6(3):82. doi: 10.3390/diseases6030082.

  PMID: 30227643 BACKGROUND

• Elmanfi S, Ma X, Sintim HO, Kononen E, Syrjanen S, Gursoy UK. Quorum-sensing molecule dihydroxy-2,3-pentanedione and its analogs as regulators of epithelial integrity. J Periodontal Res. 2018 Jun;53(3):414-421. doi: 10.1111/jre.12528. Epub 2018 Jan 17.

  PMID: 29344966 BACKGROUND

• Laserson U, Vigneault F, Gadala-Maria D, Yaari G, Uduman M, Vander Heiden JA, Kelton W, Taek Jung S, Liu Y, Laserson J, Chari R, Lee JH, Bachelet I, Hickey B, Lieberman-Aiden E, Hanczaruk B, Simen BB, Egholm M, Koller D, Georgiou G, Kleinstein SH, Church GM. High-resolution antibody dynamics of vaccine-induced immune responses. Proc Natl Acad Sci U S A. 2014 Apr 1;111(13):4928-33. doi: 10.1073/pnas.1323862111. Epub 2014 Mar 17.

  PMID: 24639495 BACKGROUND

• Zhang G, Zhang Z, Pei Y, Hu W, Xue Y, Ning R, Guo X, Sun Y, Zhang Q. Biological and clinical significance of radiomics features obtained from magnetic resonance imaging preceding pre-carbon ion radiotherapy in prostate cancer based on radiometabolomics. Front Endocrinol (Lausanne). 2023 Oct 20;14:1272806. doi: 10.3389/fendo.2023.1272806. eCollection 2023.

  PMID: 38027108 BACKGROUND

• Buizza G, Paganelli C, D'Ippolito E, Fontana G, Molinelli S, Preda L, Riva G, Iannalfi A, Valvo F, Orlandi E, Baroni G. Radiomics and Dosiomics for Predicting Local Control after Carbon-Ion Radiotherapy in Skull-Base Chordoma. Cancers (Basel). 2021 Jan 18;13(2):339. doi: 10.3390/cancers13020339.

  PMID: 33477723 BACKGROUND

• Ma L, Li Y, Sakamoto Y, Xie L, Suzuki S, Yoshida Y, Sui L, Guo G, Wen J, Ren W, Kakimi K, Osada K, Takahashi A, Shimokawa T. Optimal radiation dose to induce an abscopal effect by combining carbon-ion radiotherapy and anti-CTLA4 antibody. Neoplasia. 2025 Feb;60:101099. doi: 10.1016/j.neo.2024.101099. Epub 2024 Dec 13.

  PMID: 39674115 BACKGROUND

• Shiba S, Okonogi N, Kato S, Wakatsuki M, Kobayashi D, Kiyohara H, Ohno T, Karasawa K, Nakano T, Kamada T. Clinical Impact of Re-irradiation with Carbon-ion Radiotherapy for Lymph Node Recurrence of Gynecological Cancers. Anticancer Res. 2017 Oct;37(10):5577-5583. doi: 10.21873/anticanres.11991.

  PMID: 28982873 BACKGROUND

• Okonogi N, Ando K, Murata K, Wakatsuki M, Noda SE, Irie D, Tsuji H, Shozu M, Ohno T. Multi-Institutional Retrospective Analysis of Carbon-Ion Radiotherapy for Patients with Locally Advanced Adenocarcinoma of the Uterine Cervix. Cancers (Basel). 2021 May 31;13(11):2713. doi: 10.3390/cancers13112713.

  PMID: 34072676 BACKGROUND

• Wang X, Chen X, Li G, Han X, Gao T, Liu W, Tang X. Application of Carbon Ion and Its Sensitizing Agent in Cancer Therapy: A Systematic Review. Front Oncol. 2021 Jul 5;11:708724. doi: 10.3389/fonc.2021.708724. eCollection 2021.

  PMID: 34290989 BACKGROUND

• Tinganelli W, Durante M. Carbon Ion Radiobiology. Cancers (Basel). 2020 Oct 17;12(10):3022. doi: 10.3390/cancers12103022.

  PMID: 33080914 BACKGROUND

• Reinhardt JM, Christensen GE, Hoffman EA, Ding K, Cao K. Registration-derived estimates of local lung expansion as surrogates for regional ventilation. Inf Process Med Imaging. 2007;20:763-74. doi: 10.1007/978-3-540-73273-0_63.

  PMID: 17633746 BACKGROUND

• Paskett ED. Breast cancer-related lymphedema: attention to a significant problem resulting from cancer diagnosis. J Clin Oncol. 2008 Dec 10;26(35):5666-7. doi: 10.1200/JCO.2008.19.0850. Epub 2008 Nov 10. No abstract available.

  PMID: 19001317 BACKGROUND

• Nixon PL, Rangan A, Kim YG, Rich A, Hoffman DW, Hennig M, Giedroc DP. Solution structure of a luteoviral P1-P2 frameshifting mRNA pseudoknot. J Mol Biol. 2002 Sep 20;322(3):621-33. doi: 10.1016/s0022-2836(02)00779-9.

  PMID: 12225754 BACKGROUND

• Costabile M, Hii CS, Robinson BS, Rathjen DA, Pitt M, Easton C, Miller RC, Poulos A, Murray AW, Ferrante A. A novel long chain polyunsaturated fatty acid, beta-Oxa 21:3n-3, inhibits T lymphocyte proliferation, cytokine production, delayed-type hypersensitivity, and carrageenan-induced paw reaction and selectively targets intracellular signals. J Immunol. 2001 Oct 1;167(7):3980-7. doi: 10.4049/jimmunol.167.7.3980.

  PMID: 11564817 BACKGROUND

• Haeker M, Wu X, Abramoff M, Kardon R, Sonka M. Incorporation of regional information in optimal 3-D graph search with application for intraretinal layer segmentation of optical coherence tomography images. Inf Process Med Imaging. 2007;20:607-18. doi: 10.1007/978-3-540-73273-0_50.

  PMID: 17633733 BACKGROUND

• Anand KJ, Barton BA, McIntosh N, Lagercrantz H, Pelausa E, Young TE, Vasa R. Analgesia and sedation in preterm neonates who require ventilatory support: results from the NOPAIN trial. Neonatal Outcome and Prolonged Analgesia in Neonates. Arch Pediatr Adolesc Med. 1999 Apr;153(4):331-8. doi: 10.1001/archpedi.153.4.331.

  PMID: 10201714 BACKGROUND

• Thomson DP, Brown R, Dunn K, Scanlan E. Effect of a ground critical care transport service on air medical helicopter utilization. Prehosp Emerg Care. 1999 Apr-Jun;3(2):136-9. doi: 10.1080/10903129908958922.

  PMID: 10225647 BACKGROUND

• Xia KQ, Sun C, Zhou SQ. Particle image velocimetry measurement of the velocity field in turbulent thermal convection. Phys Rev E Stat Nonlin Soft Matter Phys. 2003 Dec;68(6 Pt 2):066303. doi: 10.1103/PhysRevE.68.066303. Epub 2003 Dec 17.

  PMID: 14754311 BACKGROUND

• Yawn BP. Vaccines and physician behavior. Arch Pediatr Adolesc Med. 1999 Apr;153(4):326-7. doi: 10.1001/archpedi.153.4.326. No abstract available.

  PMID: 10201713 BACKGROUND

• Kazdin AE, Wassell G. Therapeutic changes in children, parents, and families resulting from treatment of children with conduct problems. J Am Acad Child Adolesc Psychiatry. 2000 Apr;39(4):414-20. doi: 10.1097/00004583-200004000-00009.

  PMID: 10761342 BACKGROUND

• Latz S, Wolf AW, Lozoff B. Cosleeping in context: sleep practices and problems in young children in Japan and the United States. Arch Pediatr Adolesc Med. 1999 Apr;153(4):339-46. doi: 10.1001/archpedi.153.4.339.

  PMID: 10201715 BACKGROUND

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

Drug Therapy

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Hanmei Lou, MD

  Zhejiang Cancer Hospital

  STUDY CHAIR

Central Study Contacts

Zhuomin Yin, MD

CONTACT

yinzm@zjcc.org.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Masking Details: Open-label study, no masking performed
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Prospective single-arm clinical study

Study Record Dates

• First Submitted: June 29, 2026
• First Posted: July 14, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2030
• Last Updated: July 14, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)