Trial Title:
Neoadjuvant Cadonilimab Combined With Anlotinib in Locally Advanced Resectable Esophageal Squamous Cell Carcinoma
NCT ID:
NCT06426797
Condition:
Locally Advanced Esophageal Squamous Cell Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Esophageal Squamous Cell Carcinoma
Conditions: Keywords:
esophageal squamous cell carcinoma
neoadjuvant immunotherapy
pathological complete response
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
Patients with locally advanced resectable esophageal squamous cell carcinoma
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Cadonilimab plus anlotinib
Description:
cadonilimab (10mg/Kg, ivgtt, d1) and anlotinib (12mg, P.O., d1-d14) on a 21-day regimen
for 3 cycles
Arm group label:
locally advanced ESCC
Summary:
The goal of this clinical trial is to learn if cadonilimab combined with anlotinib can be
a safe and effective neoadjuvant therapy in patients with locally advanced resectable
esophageal squamous cell carcinoma (ESCC). The main questions it aims to answer are:
What level of pathological complete response (pCR) rate can be achieved with this
neoadjuvant regimen? Is this neoadjuvant regimen safe enough with acceptable toxicity?
Participants will:
Receive cadonilimab (10mg/Kg, ivgtt, d1) and anlotinib (12mg, P.O., d1-d14) on a 21-day
regimen for 3 cycles.
Undertake radical resection of ESCC after neoadjuvant therapy if there is no surgical
contraindication.
Accept an follow-up for 2 years after surgery.
Detailed description:
Esophageal cancer has a high incidence in China, among which esophageal squamous cell
carcinoma is the most common. Neoadjuvant chemoradiotherapy combined with surgery is
currently the recommended treatment modality for locally advanced esophageal cancer, but
the side effects of chemoradiotherapy are serious, which increases the risk of surgery.
Immune checkpoint inhibitors have made significant progress in the field of cancer
treatment in recent years, and have now become an important treatment method for advanced
and metastatic esophageal cancer. Several trials on neoadjuvant immuno-chemotherapy
demonstrated better outcomes with acceptable toxicity compared to traditional
chemoradiotherapy. Cadonilimab is a dual immune antibody drug comprised of PD-1 antibody
and CTLA-4 antibody, which has the anti-tumor effect of two immune checkpoint pathways at
the same time.
On the other hand, angiogenesis plays a vital role in the growth and metastasis of
tumors, and anti-angiogenic drugs have become an important part of cancer treatment.
Anlotinib is an oral, small molecule anti-angiogenic targeted agent that has been
approved for use in a variety of cancer treatments.
This study plans to conduct a prospective study of cadonilimab combined with anlotinib in
the neoadjuvant treatment of resectable esophageal squamous cell carcinoma, and aims to
explore the efficacy and safety of this neoadjuvant regimen that avoids chemoradiotherapy
in locally advanced resectable esophageal squamous cell carcinoma.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Able to provide written informed consent and understand and agree to comply with the
requirements of this study as well as the assessment schedule.
2. Be at least 18 years of age on the date of signing the ICF.
3. Histopathologically confirmed esophageal squamous cell carcinoma: the clinical stage
is T1-2N1-3M0, T2 (diameter≥3 cm) N0M0 or T3-4aN0-3M0 (stage II-IVA), and the
staging should be based on the AJCC 8th edition esophageal cancer staging system.
4. Patients are asked to provide an archival tumor tissue sample (FFPE tissue block or
approximately 15 [≥6] freshly cut unstained FFPE sections) and a pathology report of
this baseline sample. If no archival sample is available or the sample is not
available, a biopsy sample is requested at baseline.
5. Prior to study enrollment, patients are evaluated by thoracic surgeon in charge of
surgery to verify that they meet the study requirements for R0 resection with
radical curative intent.
6. Cardiac and pulmonary function is good, and surgical resection for curative purposes
is confirmed, and cardiopulmonary function tests and respiratory or cardiology
consultation can be completed if necessary.
7. Measurable disease as assessed by the investigator according to RECIST version 1.1.
8. Eligible for anlotinib treatment.
9. ECOG performance status ≤ 2 points.
10. ≤ 14 days prior to enrollment, the following laboratory test values during the
screening period suggest that the patient has good organ function:
- Patient has not had a blood transfusion or use of growth factor supportive
therapy within ≤14 days prior to blood draw, when the following items are
tested prior to enrollment:
- Absolute neutrophil count ≥ 1.5 x 109/L
- Platelet ≥ 75×109/L
- Hemoglobin ≥ 90 g/L
- Glomerular filtration rate (GFR) estimated by the Cooperative Equation for
Epidemiology of Chronic Kidney Disease ≥45mL/min/1.73 m2.
- Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN) (total bilirubin must
be <3 ×ULN in patients with Gilbert's syndrome).
- AST and ALT≤2.5 ×ULN.
- Patients not receiving anticoagulant therapy: International normalized ratio or
activated partial prothrombin time ≤ 1.5× ULN.
11. Females of childbearing potential must be willing to practice highly effective
contraception for the duration of the study, and for ≥120 days after the last dose
of cadonilimab or anlotinib, whichever occurs later, and have a negative urine or
serum pregnancy test result within ≤7 days prior to enrollment.
Exclusion Criteria:
1. Previous treatment for current esophageal cancer, including chemotherapy or
radiotherapy.
2. Prior receipt of antibodies or drugs targeting immune checkpoint pathways, including
but not limited to anti-cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4),
anti-PD-1, and anti-PD-L1 therapeutic antibodies.
3. Patients with non-squamous cell carcinoma.
4. Presence of locally advanced, unresectable disease, regardless of disease stage and
presence or absence of metastases (stage IV).
5. Active autoimmune disease or history of autoimmune disease that may recur.
Note: Patients with the following conditions do not need to be excluded and can
proceed for further enrollment screening:
- Well-controlled type I diabetes
- Hypothyroidism (as long as it is treated with hormone replacement therapy
alone)
- Well-controlled celiac disease
- Skin conditions that do not require systemic treatment (e.g., vitiligo,
psoriasis, alopecia)
- Any other illness that is not expected to recur in the absence of an external
trigger
6. Any active malignancy in the ≤ 2 years prior to enrollment, with the exception of
the specific cancers studied in this study and cancers that have recured locally
after radical therapy (e.g., resected basal cell or squamous cell skin cancer,
superficial bladder cancer, cervical or breast carcinoma in situ).
7. Any condition requiring systemic treatment with corticosteroids (prednisone or
equivalent> 10 mg/day) or other immunosuppressive medications within ≤14 days prior
to enrollment.
Note: Patients with current or prior use of any of the following steroid regimens do
not need to be excluded:
- Adrenal replacement steroids (prednisone or equivalent> 10 mg/day)
- Topical, ocular, intra-articular, intranasal, or inhaled corticosteroids with
very low systemic absorption
- Short-term (≤7 days) prophylactic use of corticosteroids (e.g., contrast
allergy) or for the treatment of non-autoimmune diseases (e.g., delayed-type
hypersensitivity reactions caused by contact allergens)
8. Poorly controlled diabetes mellitus ≤ 14 days prior to enrollment, or abnormal
laboratory test results of potassium, sodium, or corrected calcium > grade 1
(regardless of standard medical management) or ≥ grade 3 hypoalbuminemia.
9. Has a history of interstitial lung disease, non-infectious pneumonitis, or poorly
controlled diseases, including pulmonary fibrosis, acute lung disease, etc.
10. Severe chronic or active infection requiring systemic antibacterial, antifungal or
antiviral therapy, including tuberculosis infection, etc. Severe infection within 4
weeks prior to enrollment, including but not limited to hospitalization for
complications of infection, bacteremia, or severe pneumonia.
11. Known history of HIV virus infection.
12. Patients with untreated chronic hepatitis B or HBV carriers with hepatitis B virus
(HBV) DNA ≥ 500 IU/mL, or patients with active hepatitis C virus (HCV) should be
excluded.
Note: Patients with inactive hepatitis B surface antigen (HBsAg) carriers, treated
and stable hepatitis B carriers (HBV DNA < 500 IU/mL), and cured hepatitis C
patients can be enrolled.
13. Any major surgical procedure requiring general anesthesia ≤ 28 days prior to
enrollment.
14. Previous allogeneic stem cell transplantation or organ transplantation.
15. Any of the following cardiovascular risk factors:
- Cardiogenic chest pain within 28 days prior to enrollment, defined as moderate
pain with instrumental limitation of activities of daily living.
- Symptomatic pulmonary embolism within 28 days prior to enrollment.
- Any history of acute myocardial infarction within 6 months prior to enrollment.
- Any history of heart failure consistent with New York Heart Association
Classification Class III or IV≤ 6 months prior to enrollment.
- Any ≥ grade 2 ventricular arrhythmic event within 6 months prior to enrollment
(inclusive).
- Any history of cerebrovascular accident within 6 months prior to enrollment.
- Hypertension that remains uncontrolled with standard antihypertensive
medication within 28 days prior to enrollment.
- Syncope or seizures ≤ 28 days prior to enrollment.
16. History of severe allergic reaction to chimeric or humanized antibodies or fusion
proteins.
17. Received any other chemotherapy, immunotherapy (e.g., interleukin, interferon,
thymosin), or any investigational therapy during the study period.
18. Patients who have not returned to baseline or stable levels of toxic side effects
(due to prior antineoplastic therapy) unless the AE is not considered to pose a
safety risk (e.g., alopecia, neuropathy, and specific laboratory abnormalities).
19. Received a live vaccine ≤ 4 weeks prior to enrollment. Note: Seasonal influenza
vaccines are usually inactivated and are therefore permitted. Intranasal vaccination
is a live vaccine, so it is not allowed.
20. Has an underlying medical condition (including laboratory abnormalities) or
alcohol/drug abuse or dependence that, in the opinion of the investigator, is
detrimental to study drug administration or affects the interpretation of drug
toxicity or adverse events, or in the judgment of the investigator that the
patient's adherence during the study is not adequate that could affect compliance.
21. Participating in another therapeutic clinical study at the same time.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Start date:
May 2024
Completion date:
May 2027
Lead sponsor:
Agency:
Peking University People's Hospital
Agency class:
Other
Collaborator:
Agency:
Akeso Pharmaceuticals, Inc.
Agency class:
Other
Source:
Peking University People's Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06426797
