Trial Title:
AK104 and Low-dose Radiation in Recurrent/Metastatic HNSCC After Failure of First-line Systemic Therapy
NCT ID:
NCT06494995
Condition:
Head and Neck Squamous Cell Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Capecitabine
Conditions: Keywords:
low-dose radiotherapy
low-dose radiation
cadonilimab
CTLA-4
PD-1
Stereotactic Body Radiation Therapy
Hybrid radiation
Immune modulation
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Cadonilimab
Description:
a PD-1/CTLA-4 dual antibody
Arm group label:
Hybrid RT
Arm group label:
Metronomic chemotherapy and LDRT
Intervention type:
Radiation
Intervention name:
Low-dose radiotherapy
Description:
Low-dose radiation
Arm group label:
Hybrid RT
Arm group label:
Metronomic chemotherapy and LDRT
Intervention type:
Radiation
Intervention name:
SBRT
Description:
selected leisions to treat with stereotactic radiotherapy
Arm group label:
Hybrid RT
Intervention type:
Drug
Intervention name:
Capecitabine
Description:
Capecitabine metronomic chemotherapy
Arm group label:
Metronomic chemotherapy and LDRT
Summary:
Currently, there is a lack of high-quality clinical evidence for subsequent treatment
options for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) after
first-line treatment, especially for subsequent treatment after first-line therapy
combined with PD-1 inhibitors. Increasing evidence suggests that low-dose radiation
(LDRT) can reshape the tumor microenvironment.Cadonilimab is a bispecific antibody that
specifically binds to CTLA-4 and PD-1 proteins in the human body.
Considering that low-dose radiotherapy and cadonilimab both have immunomodulatory
effects, this study intends to select recurrent metastatic HNSCC patients who have failed
first-line and above treatment to explore the safety and efficacy of cadonilimab combined
with low-dose radiotherapy.
Detailed description:
Currently, there is a lack of high-quality clinical evidence for subsequent treatment
options for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) after
first-line treatment, especially for subsequent treatment after first-line therapy
combined with PD-1 inhibitors. Increasing evidence suggests that low-dose radiation
(LDRT) can reshape the tumor microenvironment, polarize macrophages towards M1, and M1
macrophages secrete chemokines to promote the recruitment of effector T cells while
inducing vascular normalization.
Cadonilimab is a bispecific antibody that specifically binds to CTLA-4 and PD-1 proteins
in the human body. It is the first approved PD-1/CTLA-4 bispecific antibody. In June
2022, cadonilimab was approved by the NMPA for the treatment of recurrent or metastatic
cervical cancer patients after platinum-based chemotherapy failure. The drug is currently
undergoing clinical trials for other types of cancers, including non-small cell lung
cancer, hepatocellular carcinoma, gastric cancer, esophageal cancer, and nasopharyngeal
cancer.
In view of the subsequent treatment strategies for recurrent metastatic HNSCC after
first-line treatment progress, there is still a lack of high-level evidence-based medical
evidence to confirm the best recommendation for subsequent treatment. Considering that
low-dose radiotherapy and cadonilimab both have immunomodulatory effects, this study
intends to select recurrent metastatic HNSCC patients who have failed first-line and
above treatment to explore the safety and efficacy of cadonilimab combined with low-dose
radiotherapy.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Patients who signed the informed consent and were willing to complete the study
according to the protocol;
2. Aged ≥18 years and ≤75 years;
3. Histologically confirmed head and neck squamous cell carcinoma;
4. Patients with recurrent and metastatic head and neck squamous cell carcinoma, with
progression on first-line treatment or above; or locally advanced head and neck
squamous cell carcinoma, with recurrence and metastasis within 6 months after
radical radiotherapy;
5. For patients with locally recurrent head and neck squamous cell carcinoma, those who
are not suitable for local treatment after multidisciplinary evaluation of head and
neck tumors;
6. At least one measurable lesion before treatment, that is, meeting the "measurable
lesion" requirement in the RECIST 1.1 standard;
7. Expected survival period>3 months;
8. ECOG score 0-2 points;
9. Good organ function: meet the following requirements:
1. Absolute neutrophil count (ANC) ≥1.5×109/L;
2. Platelet count ≥100×109/L;
3. Hemoglobin ≥9g/dL;
4. Serum albumin ≥2.8g/dL;
5. Total bilirubin ≤1.5×ULN, ALT, AST and/or ALP ≤3×ULN;
6. Serum creatinine ≤1.5×ULN and creatinine clearance ≥60 mL/min (Cockcroft-Gault,
see Appendix 3);
7. Activated partial thromboplastin time (APTT) and international normalized ratio
(INR) ≤1.5× ULN (screening is allowed for patients who are taking stable doses
of anticoagulant therapy such as low molecular weight heparin or warfarin and
whose INR is within the expected therapeutic range of the anticoagulant);
10. Patients with hepatitis B virus (HBV) infection and inactive/asymptomatic HBV
carriers, or patients with chronic or active HBV, will be allowed to enroll if HBV
DNA <500 IU/mL (or 2500 copies/mL) at screening. Patients with positive hepatitis C
antibodies will be allowed to enroll if HCV-RNA is negative at screening.
11. Women of childbearing age need to have a negative urine or serum pregnancy test
result within ≤7 days before treatment. And use a medically approved contraceptive
method (such as intrauterine device, birth control pills or condoms) during the
study treatment, at least 3 months after the last use of cadonilimab, and at least 6
months after the last use of chemotherapy;
12. Male subjects who are not sterilized must be willing to use a medically approved
contraceptive method (such as intrauterine device, birth control pills or condoms)
during the study treatment, at least 3 months after the last use of cadonilimab, and
at least 6 months after the last use of chemotherapy.
Exclusion Criteria:
1. Patients who have received anti-CTLA-4 antibodies, or any other antibodies or drugs
targeting T cell co-stimulation or checkpoint pathways, or small molecule tyrosine
kinase inhibitors, including lenvatinib, anlotinib, apatinib, etc.;
2. Patients with symptoms of spinal cord compression, risk of pathological fracture, or
emergency surgery and/or radiotherapy due to other medical needs;
3. Patients with a history of gastrointestinal perforation and/or fistula within 6
months before enrollment (if the gastrointestinal perforation or fistula has been
surgically removed, enrollment is allowed);
4. Patients with necrotic lesions within 4 weeks before enrollment, or tumors directly
invading the trachea, bronchus, esophagus, or arteries, and who are judged by the
investigator to have a risk of major bleeding;
5. Patients with other malignant tumors in the past or at the same time (except for
malignant tumors that have been cured and have survived without cancer for more than
3 years, such as basal cell carcinoma of the skin, carcinoma in situ of the cervix,
and papillary thyroid carcinoma);
6. Uncontrolled clinical symptoms or diseases of the heart, such as: a. NYHA heart
failure of grade II or above; b. Unstable angina pectoris; c. Myocardial infarction
within 1 year; d. Patients with clinically significant supraventricular or
ventricular arrhythmias requiring clinical intervention;
7. Received any of the following treatments:
1. Received any research drug within 4 weeks before the first use of the study
drug;
2. Enrolled in another clinical study at the same time, unless it is an
observational (non-interventional) clinical study;
3. Subjects who need to be given corticosteroids (daily prednisone equivalent dose
of >10 mg) or other immunosuppressants for systemic treatment within 2 weeks
before the first use of the study drug, except for the use of corticosteroids
for local inflammation and prevention of allergies, nausea and vomiting. Other
special cases need to be communicated with the investigator. In the absence of
active autoimmune diseases, inhaled or topical steroids and adrenocortical
hormone replacement at a dose of >10 mg/day prednisone are allowed;
4. Patients who have received anti-tumor vaccines or have received vaccines
(including live vaccines or inactivated vaccines) within 4 weeks before the
first administration of the study drug;
5. Patients who have undergone major surgery or severe trauma within 4 weeks
before the first use of the study drug;
8. The toxicity of previous anti-tumor treatment has not recovered to ≤CTCAE grade 1
(except for sequelae of alopecia and neurotoxicity related to previous platinum
treatment) or the level specified by the inclusion/exclusion criteria;
9. Severe infection (CTCAE>2) occurred within 4 weeks before the first use of the study
drug, such as severe pneumonia, bacteremia, infectious complications, etc. requiring
hospitalization; baseline chest imaging examinations indicate active lung
inflammation, symptoms and signs of infection within 4 weeks of the first use of the
study drug, or the need for oral or intravenous antibiotic treatment;
10. Active autoimmune diseases or a history of autoimmune diseases (such as interstitial
pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism,
hypothyroidism, including but not limited to these diseases or syndromes); but not
including autoimmune-mediated hypothyroidism treated with stable doses of thyroid
replacement hormone; type 1 diabetes using stable doses of insulin; patients with
vitiligo or healed childhood asthma/allergies who do not require any intervention as
adults;
11. Patients with a history of immunodeficiency, including HIV positive, or other
acquired or congenital immunodeficiency diseases, or a history of organ
transplantation and allogeneic bone marrow transplantation;
12. Patients with a history of interstitial lung disease (excluding radiation pneumonia
without steroid treatment) or non-infectious pneumonia;
13. Patients with active pulmonary tuberculosis infection found through medical history
or CT examination, or patients with a history of active pulmonary tuberculosis
infection within 1 year before enrollment, or patients with a history of active
pulmonary tuberculosis infection more than 1 year ago but without formal treatment;
14. Subjects with active hepatitis B (HBV DNA ≥500 IU/mL or 2500 copies/mL), hepatitis C
(positive hepatitis C antibody, and HCV-RNA is higher than the detection limit of
the analytical method);
15. known history of psychotropic drug abuse, alcoholism or drug abuse;
16. pregnant or lactating women;
17. the researcher judges that the subject has other factors that may force him to
terminate the study midway, such as other serious diseases (including mental
illness) requiring combined treatment, serious abnormal laboratory test values,
family or social factors that may affect the safety of the subject or the collection
of trial data.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Fudan University Shanghai Cancer Center
Address:
City:
Shanghai
Zip:
200032
Country:
China
Contact:
Last name:
Yu Wang, M.D.
Phone:
+8618017313971
Email:
neck130@hotmail.com
Contact backup:
Last name:
Xiaomin Ou, M.D.
Phone:
+8618017317872
Email:
0456218@fudan.edu.cn
Investigator:
Last name:
Yu Wang, M.D.
Email:
Principal Investigator
Investigator:
Last name:
Xiaomin Ou, M.D.
Email:
Principal Investigator
Start date:
July 1, 2024
Completion date:
July 1, 2028
Lead sponsor:
Agency:
Fudan University
Agency class:
Other
Source:
Fudan University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06494995
