Using Toripalimab with Chemoradiotherapy for Advanced Cervical Cancer

Toripalimab Combined With Chemoradiotherapy Followed by Toripalimab Maintenance Therapy for High-risk Locally Advanced Cervical Cancer: the Phase II Single-arm TorCH -CC Study

This study is testing if adding a new, more affordable drug called Toripalimab to standard chemotherapy and radiation can help patients with advanced cervical cancer live longer without their cancer getting worse.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 130 (estimated)
• Ages: 18 Years to 70 Years
• Sex: Female
• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences (other)
• Drugs / interventions: chemotherapy, prednisone, Toripalimab, pembrolizumab
• Locations: 1 site (Beijing, Beijing)
• Trial ID: NCT06416696 on ClinicalTrials.gov

What this trial studies

This phase II clinical study evaluates the safety and efficacy of Toripalimab, a PD-1 inhibitor, in combination with chemoradiotherapy (CRT) for patients with high-risk locally advanced cervical cancer (HR-LACC). The study aims to improve the 2-year progression-free survival rate, which is currently low for HR-LACC patients. By utilizing Toripalimab, which is more affordable than other similar treatments, the study seeks to enhance treatment accessibility and patient outcomes in China. A total of 130 patients will be enrolled, and the primary endpoint will focus on progression-free survival over two years.

Who should consider this trial

Good fit: Ideal candidates include patients aged 18 to 70 with confirmed stages III-IVA cervical cancer who have not received prior treatment.

Not a fit: Patients with central nervous system diseases or those who have previously undergone surgery, radiotherapy, or systemic anticancer therapy for cervical cancer may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve survival rates for patients with high-risk locally advanced cervical cancer.

How similar studies have performed: Previous studies have shown success with similar approaches using PD-1 inhibitors in conjunction with chemoradiotherapy, indicating potential for this treatment to be effective.

Eligibility criteria

Inclusion Criteria:

1. Patients with histologically confirmed cervical squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma.
2. FIGO 2018 staging criteria classifying the disease as stages III-IVA.
3. Age range from 18 to 70 years inclusive.
4. No prior receipt of surgery, radiotherapy, or systemic anticancer therapy for the treatment of cervical cancer.
5. No previous exposure to the study drug.
6. Presence of at least one measurable or evaluable lesion as per RECIST version 1.1, with the measurable lesion exhibiting a longest diameter of ≥10 mm on spiral CT scan or a shortest diameter of ≥15 mm for enlarged lymph nodes, which has not been previously irradiated.
7. Absence of central nervous system diseases, both primary and metastatic.
8. WHO/ECOG performance status score of 0-1.
9. Anticipated survival duration of at least 12 weeks.
10. Adequate organ function within the following parameters (without the use of any blood components, cytokines, or growth factors within 14 days prior to randomization):

    1. Absolute neutrophil count (ANC) ≥1.5×10\^9/L
    2. Platelet count ≥90×10\^9/L
    3. Hemoglobin level ≥90 g/L
    4. Serum albumin level ≥30 g/L
    5. Bilirubin level ≤1.5 times the upper limit of normal (ULN)
    6. Alanine transaminase (ALT) and aspartate transaminase (AST) levels ≤3×ULN
    7. Serum creatinine level ≤1.5×ULN
    8. Thyroid-stimulating hormone (TSH) level ≤1×ULN (with eligibility also extended to patients with free triiodothyronine \[FT3\] or free thyroxine \[FT4\] levels ≤1×ULN).
11. For women of childbearing potential not undergoing surgical sterilization, a negative serum pregnancy test (hCG) within 72 hours prior to study randomization is required; breastfeeding must be absent. Additionally, the use of a medically approved contraceptive method is mandatory from the time of informed consent through the study treatment period and for 120 days following the final administration of the trial medication or 180 days after the last chemotherapy/radiotherapy session. Participants must also agree not to donate eggs for reproductive purposes or to freeze/preserve eggs for this use during the aforementioned period.
12. Provision of a tumor tissue biopsy specimen is mandatory.
13. Informed consent must be obtained with documentation.
14. Availability for follow-up assessments.

Exclusion Criteria:

* 1. Known hypersensitivity to any component of the study medication. 2. Participation in other clinical trials, with a washout period of less than 4 weeks following completion.

  3. Prior treatment with immune checkpoint inhibitors, including but not limited to other anti-PD-1 and anti-PD-L1 monoclonal antibodies.

  4. Patients requiring immunosuppressive pharmacotherapy. 5. Individuals requiring systemic or absorbable topical corticosteroids at immunosuppressive doses. Use of prednisone at a dosage greater than 10mg/day or equivalent is prohibited within two weeks of study drug administration.

  6. Presence of active autoimmune diseases or a history thereof, excluding vitiligo, resolved childhood asthma, or resolved atopic diseases. Patients with asthma requiring intermittent bronchodilator therapy or other interventions are also excluded.

  7. Active infectious processes necessitating antimicrobial therapy, including the use of antibacterial, antiviral, or antifungal agents.

  8. History of immunodeficiency, including HIV seropositivity or other acquired and congenital immunodeficiency disorders.

  9. Uncontrolled cardiac symptoms or diseases, such as NYHA class II or higher heart failure, unstable angina, myocardial infarction within the past year, atrial fibrillation, clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention, PR interval greater than 250 ms, or QTc interval ≥470 ms.

  10. A history of arterial or venous thromboembolic events within the past 6 months.

  11. Poorly controlled hypertension despite antihypertensive therapy (systolic blood pressure ≥140mmHg and/or diastolic blood pressure ≥90mmHg).

  12. Proteinuria of 2+ or higher and a 24-hour urinary protein excretion exceeding 1.0 g.

  13. Coagulopathy (INR \>2.0, PT \>16 seconds), a bleeding diathesis, or concurrent anticoagulation or thrombolytic therapy.

  14. Bilateral hydronephrosis, unless resolved by unilateral stent placement or percutaneous nephrostomy, or deemed mild and without clinical significance by the investigator.

  15. Contraindications to chemotherapy administration. 16. Contraindications to receiving brachytherapy. 17. History of other malignancies within the past 5 years, except for basal cell carcinoma and squamous cell carcinoma of the skin.

  18. Administration of live vaccines within 4 weeks preceding the first dose of the trial medication. Inactivated seasonal influenza vaccines are permissible.

  19. History of substance abuse that has not been successfully managed or presence of psychiatric disorders that may interfere with study participation.

  20. Any medical, psychiatric, or social conditions deemed by the investigator to potentially impact the subject's ability to provide informed consent, participate fully in the study, or affect the interpretability of the study results.

Where this trial is running

Beijing, Beijing

• Cancer Hospital, Chinese Academy of Medical Sciences — Beijing, Beijing, China (RECRUITING)

Study contacts

• Principal investigator: SHUANGZHENG JIA — Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Study coordinator: Shuangzheng Jia, Ph D

Conditions: Cervical Cancers