Combination treatment for recurrent cervical cancer

Cadonilimab Plus Anlotinib for Recurrent, Metastasis or Persistent Cervical Cancer

This study is testing a new combination of treatments for people with recurrent cervical cancer to see if it helps them feel better and live longer.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 35 (estimated)
• Ages: 18 Years to 75 Years
• Sex: Female
• Sponsor: Zhongnan Hospital (other)
• Drugs / interventions: cadonilimab, anlotinib, chemotherapy, immunotherapy, pembrolizumab, radiation
• Locations: 1 site (Wuhan, Hubei)
• Trial ID: NCT05817214 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the efficacy and safety of a new treatment regimen combining cadonilimab, anlotinib, and granulocyte-macrophage colony-stimulating factor (GM-CSF) for patients with recurrent, metastatic, or persistent cervical cancer. Participants will receive cadonilimab every three weeks, anlotinib orally for two weeks followed by a break, and GM-CSF injections for two weeks with breaks in between. The study will assess treatment response and identify potential biomarkers for efficacy. The treatment duration will last up to two years or until disease progression or intolerable side effects occur.

Who should consider this trial

Good fit: Ideal candidates are female patients aged 18 to 75 with recurrent, metastatic, or persistent cervical cancer who have only received standard first-line systemic treatment.

Not a fit: Patients with cervical cancer who have not received prior systemic treatment or those with other types of cancer may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat cervical cancer.

How similar studies have performed: Previous studies have shown promising results with similar immunotherapy approaches in cervical cancer, indicating potential for success with this combination.

Eligibility criteria

Inclusion Criteria:

1. Obtain informed consent signed by the patient or their legal representative;
2. Female patients aged ≥18 and ≤75 years old;
3. ECOG PS score of 0-1;
4. Expected survival period ≥6 months;
5. Pathological types include squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma originating from the cervix;
6. Can provide tumor tissue specimens archived within 2 years or willing to undergo tumor tissue biopsy to provide fresh specimens for further testing;
7. At least one evaluable lesion meeting the criteria of RECIST 1.1;
8. Have only received standard first-line systemic treatment in the past: (1) If first-line treatment does not include immunotherapy, failure of first-line treatment is sufficient (for patients who have previously achieved cure, any number of neoadjuvant or adjuvant chemotherapy cycles do not count towards the line count, unless disease progression occurs within 3 months after ≥3 cycles of neoadjuvant/adjuvant chemotherapy; for persistent disease, ≥2 cycles of previous chemotherapy can be counted as one line, otherwise not counted); (2) If first-line treatment includes immunotherapy, clinical benefit must occur after first-line treatment, namely partial or complete tumor remission, with the duration of efficacy lasting more than 6 months.
9. Sitting blood pressure in a resting state is below the normal high value (\<140/90 mmHg), or 24-hour dynamic blood pressure monitoring average blood pressure is below the normal high value (\<140/90 mmHg), regardless of whether antihypertensive drugs are being taken orally;
10. Hematological indicators meet the following criteria (not transfused or administered hematopoietic growth factor drugs within the past 7 days): white blood cell count (WBC) ≥3.5×109/L, absolute neutrophil count (ANC) ≥1.5×109/L, platelets (PLT) ≥100×109/L, hemoglobin (Hb) ≥90g/L;
11. Liver function indicators meet the following criteria: ALT and AST ≤2.5 times the upper limit of normal (ULN), bilirubin ≤1.5×ULN, albumin ≥35g/L;
12. Coagulation function indicators meet the following criteria (not receiving anticoagulant or hemostatic drug therapy): PT and APTT ≤1.5×ULN, while INR ≤1.5 ULN;
13. Renal function indicators meet the following criteria: blood urea nitrogen (BUN) and creatinine (Cr) ≤1.5×ULN, urinary protein \<2+ or 24-hour urinary protein quantification \<1g;
14. Women of childbearing age must undergo serum pregnancy testing within 7 days before initial medication, with negative results, and not be lactating. Female subjects of childbearing age must agree to use effective contraception during the study period and within 180 days after the last dose of the study drug;
15. Good compliance.

Exclusion Criteria:

Translation:

1. Any unstable systemic diseases, including but not limited to active infections within 4 weeks (defined as fever exceeding 38.5°C, evidence of bacteremia, or evidence of infectious changes in the heart, brain, kidneys, lungs, liver, and intestines), circulatory accidents within 6 months (malignant hypertensive crisis, myocardial infarction, severe/unstable angina, heart failure above NYHA class 2, clinically significant supraventricular or ventricular arrhythmias, or cerebral vascular accidents not yet recovered from or resulting in severe sequelae), uncontrolled type 2 diabetes (fasting blood glucose \>11.1 mmol/L or glycated hemoglobin \>8%), and pulmonary insufficiency (any cause leading to decreased lung function, defined as FEV1/FVC \<70%, FEV1 \<80% of predicted value).
2. History of autoimmune diseases, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, autoimmune liver diseases, systemic vasculitis, scleroderma, dermatomyositis, autoimmune hemolytic anemia;
3. Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS); active hepatitis (hepatitis B, defined as HBV-DNA ≥ 500 IU/ml; hepatitis C, defined as HCV-RNA higher than the detection limit of the assay) or combined hepatitis B and hepatitis C infection;
4. History of attenuated live vaccine administration within 28 days before the first dose of the study drug or expected attenuated live vaccine administration during the study period;
5. Tumor invasion of major blood vessels on imaging or investigator judgment indicating a high risk of tumor invasion of important vessels causing fatal bleeding or other diseases with a high risk of severe bleeding;
6. Previous treatment with anlotinib or cadonilimab;
7. Evidence of active tuberculosis infection within the past year before screening;
8. Diagnosis of any other malignant tumors, adequately treated basal cell carcinoma or squamous cell skin carcinoma, or cervical carcinoma in situ within 5 years before entering the study;
9. Major surgery within 28 days before randomization (tissue biopsy for diagnostic purposes and insertion of a central venous catheter via percutaneous puncture are allowed);
10. Active venous or arterial thromboembolic events within 6 months before randomization, such as cerebrovascular accidents (including transient ischemic attacks), deep vein thrombosis, and pulmonary embolism;
11. Previous or planned allogeneic bone marrow or solid organ transplantation;
12. Clinically significant intestinal obstruction, occurrence of intestinal repair, intestinal anastomosis, intestinal diversion, or enterocutaneous fistula for any reason at any time;
13. Participants who experienced symptoms of hemoptysis within 2 months before entering the study and had a maximum daily hemoptysis volume of approximately ≥2.5 mL. Participants who experienced significant bleeding symptoms or had a clear bleeding tendency, such as gastrointestinal bleeding, bleeding gastric ulcers, baseline fecal occult blood test ++ and above, or vasculitis, within 3 months before entering the study; known hereditary or acquired bleeding and thrombotic tendencies, such as hemophilia, coagulation disorders, thrombocytopenia, splenic hyperfunction, etc.;
14. Visible hematuria or other evidence of active urinary system bleeding;
15. Currently receiving thrombolysis or requiring long-term anticoagulant therapy with warfarin or heparin, or requiring long-term antiplatelet therapy (aspirin ≥300 mg/day or clopidogrel ≥75 mg/day);
16. Known allergy to anlotinib, cadonilimab or any of their excipients;
17. Participation in any other drug clinical studies within the previous 4 weeks before randomization or within 5 half-lives of the last study drug administration;
18. History of substance abuse, alcoholism, or drug addiction;
19. Coexisting severe cognitive impairment and inability to achieve stable mental status;
20. As judged by the investigator, patients may have other factors that could lead to premature termination of the study, such as other serious illnesses or severe laboratory abnormalities, or factors affecting the safety of the participants or the collection of trial data and samples due to family or social reasons, etc.

Where this trial is running

Wuhan, Hubei

• Zhongnan Hospital of Wuhan University — Wuhan, Hubei, China (RECRUITING)

Study contacts

• Principal investigator: Hui Qiu, Ph.D. — Wuhan University
• Study coordinator: Shaoxing Sun, M.D.

Conditions: Cervical Cancer, Cadonilimab, Anlotinib, Granulocyte-macrophage colony-stimulating factor, Immunotherapy