Induction Immunotherapy Combined With Chemotherapy Followed by Concurrent Chemoradiotherap and Immunotherapy for Cervical Cancer
Induction Immunotherapy Combined With Chemotherapy Followed by Concurrent Chemoradiotherap and Immunotherapy for Advanced Cervical Cancer: An Open-Label, Single-Arm, Phase II Trial
Tianjin Medical University Cancer Institute and Hospital
34 participants
Dec 1, 2024
INTERVENTIONAL
Conditions
Summary
To explore the efficacy and tolerability of a platinum-based regimen combined with the PD-1 antibody toripalimab administered prior to concurrent chemoradiotherapy in patients with locally advanced cervical cancer.
Eligibility
Inclusion Criteria11
- Women aged 18-75 years.
- Histologically confirmed, previously untreated locally advanced cervical cancer of squamous, adenocarcinoma, or adenosquamous type.
- At least one measurable lesion that has not received prior local therapy (non-nodal lesion ≥ 10 mm longest diameter or pathological lymph node ≥ 15 mm short axis, per RECIST 1.1).
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
- Estimated life expectancy ≥ 6 months.
- Investigator-assessed eligibility for concurrent chemoradiotherapy.
- No clinically significant active bleeding.
- Laboratory values: WBC \> 4 × 10⁹/L; platelets \> 100 × 10⁹/L.
- No history of other malignancies.
- Women of child-bearing potential must have a negative serum pregnancy test and use effective contraception throughout the study.
- Written informed consent obtained prior to any study-related procedures.
Exclusion Criteria21
- Tumor recurrence or distant metastasis at screening.
- Active autoimmune disease requiring systemic therapy, or any chronic condition requiring long-term high-dose corticosteroids (≥10 mg/day prednisone or equivalent) or other immunosuppressive agents.
- Systemic corticosteroids (\>10 mg/day prednisone or equivalent) or any other immunosuppressive drugs within 14 days before first study dose or anticipated during the study.
- Live-attenuated vaccination within 30 days before first dose or planned during the study.
- Prior organ transplantation or known HIV infection.
- Active hepatitis B (HBV DNA \>2000 IU/mL or \>10⁴ copies/mL, or HBsAg positive) or active hepatitis C (HCV RNA \>10³ copies/mL); co-infection with both viruses is also excluded.
- Prior therapy with any agent targeting PD-1, PD-L1, PD-L2, CD137, CTLA-4 (e.g., ipilimumab), or any other antibody or drug that modulates T-cell co-stimulation or checkpoint pathways.
- Known hypersensitivity to monoclonal antibodies, fusion proteins, or any excipients in the investigational products.
- History of another malignancy within the past 5 years, except adequately treated cervical carcinoma in situ, basal-cell carcinoma of the skin, or other localized malignancies considered cured.
- Severe non-surgical comorbidity or acute infection.
- Peripheral neuropathy \> Grade 1 (NCI-CTCAE).
- Inadequate hematologic or organ function:
- WBC \< 4.0 × 10⁹/L, ANC \< 1.5 × 10⁹/L, platelets \< 100 × 10⁹/L, Hb \< 90 g/L
- TBIL \> 1.5 × ULN, ALT/AST \> 2.5 × ULN, BUN \> 1.5 × ULN, creatinine \> 1.5 × ULN
- Symptomatic brain metastases.
- Clinically significant cardiac arrhythmias, myocardial ischemia, severe conduction block, heart failure, or severe valvular disease.
- Severe bone-marrow failure.
- Uncontrolled psychiatric illness.
- Pregnant or lactating women.
- Investigator-judged unsuitability for the trial.
- Concurrent participation in another interventional clinical study.
Interventions
Induction chemo-immunotherapy (platinum-based tri-weekly regimen) * Paclitaxel 175 mg/m² IV on day 1 * Cisplatin 50 mg/m² IV on day 1 or carboplatin AUC 4-5 IV on day 1 * Toripalimab 240 mg IV on day 1, administered immediately before each chemotherapy infusion Cycle length: every 3 weeks Number of cycles: 2 Concurrent chemoradiotherapy (weekly regimen) * Radiation therapy delivered according to institutional protocol * Cisplatin 40 mg/m² IV once weekly * Toripalimab 240 mg IV on day 1 of every 3-week cycle, given before chemotherapy Cycle length: every 3 weeks during radiotherapy Maintenance immunotherapy • Toripalimab 240 mg IV on day 1 every 3 weeks (Q3W) Duration: 1 year (total 13 cycles)
* PTV: 6 MV photons, 1.80 Gy per fraction × 28 fractions = 50.4 Gy. * PGTVnd: 6 MV photons, 2.14 Gy per fraction × 28 fractions = 59.92 Gy. Brachytherapy:Dose prescriptions * Dose: 7.00 Gy per fraction × 4 fractions = 28.0 Gy.
Locations(1)
View Full Details on ClinicalTrials.gov
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NCT07092696