A Single-arm, Single-center, Prospective, Phase II Study of Nimotuzumab, Tislelizumab Plus Radiotherapy for Recurrent and Metastatic Cervical Cancer
Overview
- Phase
- Phase 2
- Intervention
- Nimotuzumab、Tislelizumab
- Conditions
- Cervical Cancer
- Sponsor
- Peking Union Medical College Hospital
- Enrollment
- 55
- Primary Endpoint
- Progression-free survival (PFS)
- Status
- Not yet recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
Patients with recurrent or metastatic cervical cancer have very poor prognosis. For eligible patients, radiotherapy remains the choice, which has the most effective impact on the survival periods. Epidermal growth factor receptor (EGFR) is overexpressed in cervical cancer cells, anti-EGFR therapy maybe an ideal target for the treatment of cervical cancer. This study aims to discover the progression-free survival of combination therapy with nimotuzumab (an anti-epidermal growth factor receptor [EGFR] IgG1 humanized monoclonal antibody) 、Tislelizumab and radiotherapy in recurrent or metastatic uterine cervical squamous carcinoma in a single-arm, open, phase 2 clinical trial.
Detailed Description
Nimotuzumab, is a humanized antibody recognizing with high affinity the epidermal growthfactor (EGF-R)，has shown promising efficacy and tolerable toxicity in the cervical cancer. In this study, patients with recurrent or metastatic cervical cancer, will be included in this study according to the prescribed criteria in the protocal. Nimotuzumab 400 mg/time, intravenous injection, qw; Tislelizumab 200 mg/time, q3w until disease progression, intolerable toxicity, or 24 months of medication. Assess objective response rate; progression-free survival; median overall survival and safety ( adverse event).
Investigators
Lei Li
chief physician, professor
Peking Union Medical College Hospital
Eligibility Criteria
Inclusion Criteria
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 2；
- •Have recurrent, or metastatic squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix；
- •Oligometastases and Oligo-recurrence( number of metastatic organs ≤3, and the total number of metastases ≤5), with indications for radiotherapy, and which has not been treated with systemic chemotherapy；
- •At least one measurable lesion defined by Response Evaluation Criteria in Solid Tumors (RECIST) guideline 1.1；
- •Anticipative survival period of 3 months or more；
- •Have adequate organ function as indicated by the following laboratory values： (1) Hematological：Absolute neutrophil count (ANC)≥1.5×109/L；Platelets(PLT)≥90×109/L；Hemoglobin(Hb)≥90 g/L； (2) Hepatic：Serum total bilirubin (TBIL)≤2.5×ULN；ALT 和 AST≤2×ULN； (3) Renal:BUN 和 Cr ≤ 1.5×ULN；
- •Cardiac ultrasound：LVEF≥50%；
- •A WOCBP who has a positive blood pregnancy test within 72 hours prior to randomization（Postmenopausal women who have had amenorrhea for at least 12 months are considered infertile, and women who are known to have received Tubal ligation do not require a pregnancy test）；
- •For subjects who were not menopausal or had not undergone surgical sterilization, consent to abstinence or use of an effective contraceptive method was given during treatment and at least 5 months after the last administration of the drug during study treatment;
- •Volunteer to join the study, sign informed consent, have good compliance and willing to cooperate with the follow-up.
Exclusion Criteria
- •Patients who have received prior therapy with an anti-EGFR an anti-PD-1, anti-PD-L1 agent; Has a contraindication or hypersensitivity to Macromolecular protein preparationsany and component of Nimotuzumab and Tislelizumab
- •Other malignancies diagnosed within 5 years before the first dose, excluding basal cell carcinoma of the skin, squamous cell carcinoma of the skin and papillary thyroid carcinoma;
- •Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy， prior therapy with other targeted therapy and any anti-vascular endothelial growth factor (VEGF) drug. Other anti-tumor treatments not included in this trial protocol；
- •Patients who are pregnant or nursing. Patients of childbearing potential must agree to use contraceptive measures during study therapy and for at least five months after completion of this study.
- •Patients with recto-vaginal fistula,vesicovaginal fistula, uncontrolled vaginal bleeding and no underlying process leading to fistula；
- •Major surgical procedure unrelated to cervical cancer,and has not recovered adequately from toxicity and/or complications from surgery within 4 weeks before enrollment；
- •Has a known history of human immunodeficiency virus (HIV) infection,or has other acquired, congenital immunodeficiency disease, or has a history of organ transplantation；
- •Uncontrolled hypertension , cardiac arrhythmia and pulmonary disease.Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\]reactive) or known active Hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection.
- •Has known active Central Nervous System (CNS)metastases and/or carcinomatous meningitis. Participants with known brain metastases may participate provided that the brain metastases have been previously treated (except with chemotherapy) and are radiographically stable more than 2 weeks. Known brain metastases are considered active, if any of the following criteria are: There were measurable lesions outside the central nervous system, no metastases to meninges, midbrain, pons, cerebellum, medulla oblongata or spinal cord, no previous history of intracranial hemorrhage, and steroid therapy was discontinued 14 days before the first dose of study drug.
- •Patients with clinical signs or fluids of pleural effusion, ascites, or pericardial effusion requiring drainage (required or not significantly increased within 3 days of discontinuation of drainage) may be eligible;
Arms & Interventions
Nimotuzumab, Tislelizumab group
Subjects will receive Nimotuzumab 400 mg/time, intravenous injection, qw; Tislelizumab 200 mg/time, q3w until disease progression, intolerable toxicity, or 24 months of medication
Intervention: Nimotuzumab、Tislelizumab
Outcomes
Primary Outcomes
Progression-free survival (PFS)
Time Frame: one year
Progression-free survival is defined as the time from the start of treatment with caldonirimab and nimotuzumab until the first documentation of disease progression or death due to any cause, whichever occurs first
Secondary Outcomes
- Objective response rate (ORR)(one year)
- Median Overall survival（mOS）(three years)
- Adverse events (AEs)(three years)