Trial Title:
Nituzumab Plus Serplulimab Combined With SBRT in Cervical Cancer
NCT ID:
NCT06455072
Condition:
Cervical Cancer
Conditions: Official terms:
Uterine Cervical Neoplasms
Immune Checkpoint Inhibitors
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:
Nituzumab
Description:
EGFR monoclonal antibody
Arm group label:
Nituzumab Plus Serplulimab Combined With SBRT
Other name:
monoclonal antibody
Intervention type:
Drug
Intervention name:
Serplulimab
Description:
PD-1 (programmed death receptor 1) monoclonal antibody
Arm group label:
Nituzumab Plus Serplulimab Combined With SBRT
Other name:
Immune checkpoint inhibitors
Summary:
In recurrent advanced cervical cancer, patients were prone to drug resistance who have
relapsed within prior platinum-based chemotherapy. However, immune checkpoint inhibitor's
combination therapy has become a promising strategy for advanced cervical cancer.
Epidermal Growth Factor Receptor (EGFR) is overexpressed in cervical cancer cells.
Stereotactic radiotherapy (SBRT) can enhance the efficacy of immunotherapy.
Detailed description:
In recurrent advanced cervical cancer, patients were prone to drug resistance who have
relapsed within prior platinum-based chemotherapy. However, immune checkpoint inhibitor's
combination therapy has become a promising strategy for advanced cervical cancer.
Epidermal Growth Factor Receptor (EGFR) is overexpressed in cervical cancer cells.
Stereotactic radiotherapy (SBRT) can enhance the efficacy of immunotherapy.
Nituzumab is a humanized monoclonal antibody that binds to the epidermal growth factor
receptor. Serplulimab is a fully humanized, high-affinity monoclonal antibody against
programmed cell death-1 (PD-1).
This phase II, single-arm study aims to evaluate the efficacy and safety of Nituzumab
plus Serplulimab combined with SBRT in patients with recurrent advanced cervical cancer.
Patients who have failed in standard chemotherapy，histopathologically confirmed recurrent
advanced squamous cell cervical carcinoma regardless of programmed cell death-Ligand 1
(PD-L1) expression. Patients who have achieved the response state or come to stably at
least six months after immunotherapy were allowed. There was at least one lesion for SBRT
in addition to target lesions. ECOG 0-1 were considered eligible for enrollment.
Nituzumab was given intravenously (400mg qw, 21 days per cycle), and Serplulimab was
administered intravenously (200mg once every 3 weeks).The dose was 30-50 Gy in three to
five fractions and the number of lesions was no more than four by SBRT. The treatment was
continued until disease progression, death or intolerant toxicity.
The primary endpoint was objective response rate (ORR) and the secondary endpoints
included disease control rate (DCR), progression free survival (PFS), overall survival
(OS) and safety.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
-
1) Prospective participants will be voluntarily enrolled in this research study
and will provide written informed consent, demonstrating the ability to adhere
to scheduled visits and associated procedures.
2) Individuals aged between 18 and 75 years old are eligible for inclusion. 3)
Patients with histologically or cytologically confirmed cervical squamous cell
carcinoma, along with documented disease progression that is unresponsive to
curative treatment. It should be noted that confirmation of the original
primary tumor tissue by a pathological report is required.
4) Ineligibility due to failure of standard systemic treatment for persistent,
recurrent, or metastatic cervical cancer (defined as progression or recurrence
within six months after at least one cycle of standard systemic treatment;
patients who have previously received anti-PD-1/PD-L1 antibody treatment and
achieved CR, PR, or SD≥6 months may still be considered).
5) Not suitable for local treatments such as curative surgery or radiotherapy. 6)
A minimum interval of four weeks must occur between the completion of prior
systemic therapy and administration of the investigational drug. Additionally,
any treatment-related adverse events must have resolved to CTCAE V5.0 grade ≤1
(excluding hair loss and fatigue).
7) At least one measurable lesion must serve as a target lesion according to
RECIST V1.1 criteria.
8) Presence of at least one non-target lesion amenable to SBRT is also necessary.
9) Eastern Cooperative Oncology Group Performance Status (ECOG PS) score should be
either 0 or 1.
10）Expected survival time should exceed 12 weeks 11）Female subjects capable of
reproduction need to utilize effective contraception throughout the study period and
for at least five months following their final dose of the investigational drug
12）Subjects are required to consent providing sufficient tumor tissue samples for
EGFR expression detection including archived tumor samples (paraffin blocks or an
adequate number of unstained slides meeting study requirements); if no archived
tumor tissue samples are available, subjects must agree on biopsy from the tumor
site 13）Good organ function and bone marrow hematopoietic function.
Exclusion Criteria:
1. Diagnosed with malignancies other than basal cell carcinoma, squamous cell carcinoma
of the skin, in situ carcinoma cured by surgical resection, and/or papillary thyroid
carcinoma cured by surgery within 5 years prior to the initial dose. Participants
must have pathological types other than cervical squamous cell carcinoma.
2. Participants presenting with clinical symptoms or requiring drainage due to pleural
effusion, ascites, or pericardial effusion are eligible for inclusion, except those
whose effusion does not require drainage or ceases draining within 3 days without a
significant increase.
3. Participants who are scheduled for or have previously undergone organ or bone marrow
transplantation.
4. Individuals with acute or chronic active hepatitis B or C infection, who have HBV
DNA levels greater than 200IU/ml or 103 copies/ml, or are positive for anti-HCV
antibodies with HCV-RNA levels above the detection limit may be eligible.
Additionally, individuals with acute or chronic active hepatitis B or C infection
who have been treated with nucleoside analog antiviral agents and have HBV DNA or
HCV-RNA levels below the specified criteria or below the detection limit may also be
eligible.
5. Individuals with meningeal metastasis or symptomatic central nervous system (CNS)
metastasis may be considered for this study. Furthermore, individuals with
asymptomatic brain metastasis that has been treated and symptoms stabilized for at
least 2 weeks may also qualify if they meet specific criteria: presence of
measurable lesions outside of the CNS; absence of metastasis to certain areas within
the brain; no history of intracranial hemorrhage; discontinuation of hormone therapy
at least 14 days prior to receiving the first dose of study drug.
6. Any life-threatening bleeding event within the past 3 months, including the
requirement for blood transfusion, surgical intervention or local treatment, or
ongoing pharmacological therapy.
7. Any arterial thrombosis, embolism, or ischemia within the past 6 months, such as
myocardial infarction, unstable angina, or cerebrovascular accident. A history of
any significant thromboembolic event within the past 3 months, such as deep vein
thrombosis or any other thromboembolic event (thrombosis related to a portacatheter
or central venous catheter insertion site, superficial vein thrombosis, or a stable
post-treatment thrombosis is not considered "significant" thromboembolic event).
8. Hepatic vein thrombus involving both the hepatic trunk and the left and right
branches, or involving both the trunk and the superior mesenteric vein, inferior
vena cava; superior vena cava thrombus, superior vena cava syndrome.
9. Tumor invasion of surrounding important organs or blood vessels (such as the great
vessels of the mediastinum, the superior vena cava, the inferior vena cava, the
abdominal aorta, the iliac vessels, the trachea, the esophagus, etc.), or the risk
of developing a tracheo-esophageal fistula or an esophago-pleural fistula.
10. Uncontrollable hypertension, with a systolic blood pressure of ≥150mmHg or a
diastolic blood pressure of ≥100mmHg, history of hypertension crisis or hypertension
cerebral infarction.
11. Symptomatic congestive heart failure (New York Heart Association classification
II-IV). Symptomatic or uncontrolled arrhythmia. QT interval prolongation,
QTcF>470ms.
12. Severe bleeding tendency or coagulation disorder, or currently receiving
thrombolytic therapy.
13. History of gastrointestinal perforation and/or fistula within the past 6 months,
history of bowel obstruction (including incomplete bowel obstruction requiring
parenteral nutrition), inflammatory bowel disease or extensive bowel resection
(partial colon resection or extensive small bowel resection with chronic diarrhea),
Crohn's disease, ulcerative colitis, or chronic diarrhea.
14. History of interstitial pneumonitis, drug-induced pneumonitis, radiation
pneumonitis, idiopathic pneumonitis, or active pneumonitis. 15) Active tuberculosis
(TB), who are currently receiving anti-TB treatment or have received anti-TB
treatment within 1 year prior to the start of the study.
16) Individuals with Human Immunodeficiency Virus (HIV) infection (HIV 1/2 antibody
positive), known active syphilis infection.
17) Severe infections that are active or not well controlled. A severe infection within
4 weeks prior to the first dose, including but not limited to hospitalization due to
infection, sepsis, or severe pneumonia complications.
18) Oral or intravenous administration of therapeutic antibiotics within 1 week prior to
the start of the study.
19) Active systemic autoimmune diseases or a history of such disease within the past 2
years (Psoriasis, alopecia, vitiligo, or Graves' disease that do not require
systemic treatment within the past 2 years, hypothyroidism that only requires
thyroid hormone replacement therapy, and type 1 diabetes that only requires insulin
replacement therapy can be included). A history of primary immunodeficiency is
known. Only individuals with positive autoimmune antibodies need to be confirmed by
the investigator for the presence of autoimmune diseases. 20) You have used an
immunosuppressive drug within the past 4 weeks, excluding topical or inhaled
corticosteroids or physiological doses of systemic corticosteroids (i.e., no more
than 10 mg of prednisone or equivalent daily doses of other corticosteroids) used
for the relief of breathing difficulties associated with conditions such as asthma
or chronic obstructive pulmonary disease.
21) You have received a live attenuated vaccine within the past 4 weeks or plan to
receive one during the study.
22) You have received systemic immune stimulation therapy within the past 4 weeks.
23) You have had a major surgical procedure (craniotomy, thoracotomy, or laparotomy)
within the past 4 weeks or have an unhealed wound, ulcer, or fracture.
24) You have an uncontrolled/uncorrectable metabolic disorder or other non-malignant
tumor organ disease or systemic disease or cancer-related complications that may
result in higher medical risk and/or uncertainty in survival assessment.
25) You have any other acute or chronic disease, mental illness, or laboratory test
abnormality that may increase the risk of participating in the study or receiving
study medication, or interfere with the interpretation of study results, as
determined by the investigator.
26) You have previously received nintedanib or other anti-EGFR therapy. 27) You have
previously received sunitinib therapy. 28) Previous treatment with anti-CTLA-4
antibody.
29) Known to be allergic to any nivolumab, siltuximab component; or had a severe
allergic reaction to other monoclonal antibodies in the past.
30) Received any anti-cancer treatment within 4 weeks prior to starting the study:
systemic chemotherapy (oral fluoropyrimidine washout period is 2 weeks), endocrine
therapy, targeted therapy (small molecule targeted therapy washout period is 2 weeks
or 5.5 half-lives, whichever is longer), immunotherapy, tumor embolization therapy,
or traditional Chinese medicine treatment for anti-cancer indications, etc.
31）Pregnant or breastfeeding female patients.
Gender:
Female
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Fujian Cancer Hospital
Address:
City:
Fuzhou
Zip:
350011
Country:
China
Status:
Recruiting
Contact:
Last name:
Qin Xu
Phone:
+8613950419396
Email:
1379423879@qq.com
Start date:
February 1, 2023
Completion date:
January 31, 2025
Lead sponsor:
Agency:
Fujian Cancer Hospital
Agency class:
Other
Collaborator:
Agency:
Zhangzhou Municipal Hospital of Fujian Province
Agency class:
Other
Source:
Fujian Cancer Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06455072
