Trial Title:
Toripalimab for High-risk Locally Advanced Cervical Cancer
NCT ID:
NCT06416696
Condition:
Cervical Cancers
Conditions: Official terms:
Uterine Cervical Neoplasms
Cisplatin
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Toripalimab
Description:
1. Radiotherapy: Both external beam and brachytherapy, with radiation therapy
techniques, target delineation, prescribed doses, and organ-at-risk constraints
following established guidelines.
2. Chemotherapy: The preferred regimen is cisplatin at a dose of 40mg/m^2 administered
intravenously once weekly for 5-6 cycles; for patients intolerant to cisplatin or
with renal impairment, carboplatin (AUC=2) may be considered, also administered once
weekly.
3. Toripalimab concurrent immunotherapy: Following the regimens of phase III RCTs such
as JUPITER-02, JUPITER-06, CHOICE-01, NEOTORCH, and RENOTORCH, Toripalimab is
administered at a fixed dose of 240mg per infusion, given intravenously once every 3
weeks for three doses.
4. The concurrent chemoradiotherapy and immunotherapy phase does not exceed 8 weeks in
duration.
Arm group label:
Toripalimab combined with Chemoradiotherapy followed by Toripalimab maintenance therapy
Other name:
Radiotherapy
Other name:
Chemotherapy(cisplatin)
Summary:
This phase II clinical study assesses the efficacy and safety of Toripalimab combined
with chemoradiotherapy (CRT) followed by Toripalimab maintenance in treating high-risk
locally advanced cervical cancer (HR-LACC). Despite CRT being the standard treatment,
HR-LACC patients face poor survival outcomes. Toripalimab, a cost-effective PD-1
inhibitor, has shown promise in prior research. The primary endpoint is 2-year
progression-free survival, with the study aiming to improve treatment accessibility and
patient prognoses in China.
Detailed description:
Cervical cancer is the most prevalent malignant tumor of the female reproductive system
in China, with an estimated 150,700 new cases and 55,700 new deaths annually. Concurrent
chemoradiotherapy (CRT) remains the standard treatment for locally advanced cervical
cancer (LACC). However, for high-risk LACC (HR-LACC) patients, the 2-year
progression-free survival (PFS) rate is only 57%-62%, and the 5-year overall survival
(OS) rate is 52%-64%, which are the leading causes of patient mortality. The KEYNOTE-A18
study demonstrated that the combination of pembrolizumab and CRT reduced the progression
risk and death risk by 30% and 27%, respectively, for HR-LACC patients. Following this,
the FDA approved pembrolizumab in combination with CRT for the treatment of newly
diagnosed stages III-IVA cervical cancer in January 2024. Nevertheless, the high cost of
pembrolizumab poses a significant barrier for patients in China. Toripalimab, the first
domestically approved PD-1 inhibitor in China, has shown good safety and efficacy in
previous studies and is more affordable. This phase II, single-arm, open-label study aims
to evaluate the efficacy and safety of Toripalimab combined with CRT followed by
Toripalimab maintenance therapy in 130 patients with stages III-IVA cervical cancer. The
primary endpoint is the 2-year PFS. The study is expected to contribute to the
implementation of precision and personalized treatment for HR-LACC in China, with the
potential to improve patient survival rates and quality of life.
Criteria for 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.
Gender:
Female
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Cancer Hospital, Chinese Academy of Medical Sciences
Address:
City:
Beijing
Zip:
100021
Country:
China
Status:
Recruiting
Contact:
Last name:
SHUANGZHENG JIA
Start date:
January 9, 2024
Completion date:
December 2026
Lead sponsor:
Agency:
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Agency class:
Other
Source:
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06416696
