AzTrials
AzTrials

Esophageal Squamous Cell CarcinomaPhase 2NCT05990231

Cadonilimab/Anlotinib in Locally Advanced or Relapsed/Metastatic ESCC Patients After Failure of PD-1 Combined With Platinum-containing Chemotherapy

A Phase 2 study testing Cadonilimab combined Anlotinib in people with Esophageal Squamous Cell Carcinoma, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial summary

Advanced esophageal squamous cell carcinoma patients who have failed first-line PD-1 inhibitor combined with chemotherapy lack a standard treatment option. Second-line treatments have limited efficacy, indicating a significant unmet clinical need. Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Esophageal Squamous Cell Carcinoma
What is being tested?
Cadonilimab combined Anlotinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
35 participants
Where
1 siteChina
Study dates
1 Sep 2023to 1 Aug 2025
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Voluntarily sign a written informed consent form.
  • Age ≥18 and ≤80 years, both males and females are eligible.
  • ECOG performance status score of 0 or 1.
  • Expected survival≥3 months.
  • Patients with locally advanced or recurrent/metastatic esophageal squamous cell carcinoma confirmed by histology and/or cytology that is incurable (including curative surgery and curative radio/chemotherapy). Patients with locally advanced or recurrent/metastatic esophageal squamous cell carcinoma who have failed of PD-1 inhibitor combined with platinum-based chemotherapy , and are not allowed to receive other systemic anti-tumor treatments. Note: For patients who have received adjuvant/neoadjuvant PD-1 inhibitor combined with platinum-based chemotherapy for non-metastatic disease with curative intent, or curative platinum-based radio/chemotherapy combined with PD-1 inhibitor for locally advanced or recurrent/metastatic disease, if disease progression occurs within <6 months after the end of the last treatment, and the patients has not received other systemic anti-tumor treatments after disease progression, they are allowed to be enrolled.
  • According to RECIST v1.1, patients must have at least one measurable lesion. For patients who have received radiotherapy previously and have no other target lesions available, when there is objective evidence of significant progression after radiotherapy, the lesion treated with radiotherapy can be considered as a target lesion.
Show all 13Show fewer
  • The function of important organs meets the following requirements (excluding any blood components and growth factors used within 14 days):
  • Normal bone marrow function, neutrophils ≥1,500/mm3, platelet count ≥100,000/mm3, hemoglobin ≥5.6 mmol/L (9g/dL);
  • Normal renal function or serum creatinine ≤1.5 mg/dL and/or creatinine clearance rate ≥60 ml/min;
  • Normal liver function or bilirubin ≤1.5 times ULN, ASAT \& ALST ≤1.5 times ULN.
  • Female patients of childbearing potential must undergo a urine or serum pregnancy test within the first 3 days before the first dose (if the urine pregnancy test result cannot be confirmed as negative, a serum pregnancy test must be performed, and the serum pregnancy result will prevail), and the result must be negative. If a female patient of childbearing potential has sexual intercourse with an uncircumcised male partner, the subject must take effective contraceptive measures from the beginning of screening and must agree to continue using contraceptive methods for 120 days after the last dose of study drug; whether to stop contraception after this time point should be discussed with the investigator.
  • If an uncircumcised male subject has sexual intercourse with a female partner of childbearing potential, the subject must take effective contraceptive measures from the beginning of screening until 120 days after the last dose; whether to stop contraception after this time point should be discussed with the investigator.
  • The patient is willing and able to comply with the scheduled visits, treatment plan, laboratory tests, and other requirements of the study.

Who cannot join

  • Subjects who meet any of the following criteria will be ineligible to participate in this study:
  • Subjects who have had other malignant tumors within 3 years prior to enrollment, except those who have been cured by local treatment such as basal or squamous cell skin cancer, superficial bladder cancer, cervical or breast carcinoma in situ.
  • Subjects who are concurrently enrolled in another clinical study, unless it is an observational, non-interventional clinical study or a follow-up period of an interventional study.
  • Subjects who have received systemic anti-tumor therapy (chemotherapy, immunotherapy, etc.) for non-target lesions within 3 weeks before the first dose of study drug; palliative local therapy for non-target lesions within 2 weeks before the first dose of study drug; non-specific immunomodulatory therapy (such as interleukin, interferon, thymosin, tumor necrosis factor, etc., excluding IL-11 for thrombocytopenia) within 2 weeks before the first dose of study drug; or Chinese herbal medicine or traditional Chinese medicine with anti-tumor indications within 1 week before the first dose of study drug.
  • Subjects who have received any treatment targeting tumor immune mechanisms, such as immunotherapy other than PD-1 inhibitors (including immune checkpoint inhibitors such as anti-CTLA-4 antibodies, anti-CD47 antibodies, anti-SIRPα antibodies, anti-LAG-3 antibodies, etc.), immune checkpoint agonists (such as ICOS, CD40, CD137, GITR, OX40 antibodies, etc.), immune cell therapy, biologics, etc., other than PD-1 inhibitors.
  • Subjects who have experienced any of the following during previous PD-1 inhibitor treatment:
Show all 33Show fewer
  • Grade 3 or higher irAE caused by PD-1 inhibitor treatment (excluding endocrine system-related irAEs), irAEs that led to permanent discontinuation of treatment, grade 2 immune-related cardiac toxicity or any grade of neurologic or ophthalmologic irAE.
  • All adverse events during previous PD-1 inhibitor treatment have not been completely resolved or resolved to grade 1 before screening for this study. For subjects with grade ≥2 endocrine adverse events, if the condition is stable with appropriate alternative treatment and asymptomatic, enrollment is allowed.
  • Previous adverse events that required the use of immunosuppressive agents other than glucocorticoids or recurrence of adverse events during previous immunotherapy that required systemic use of glucocorticoids.
  • Screening imaging shows that the tumor surrounds or invades important blood vessels or organs (such as the heart and pericardium, trachea, aorta, superior vena cava, etc.), or there is obvious necrosis or cavity, and the investigator judges that entering the study would increase the risk of bleeding; there are subjects at risk of developing esophagotracheal fistula or esophageal pleural fistula.
  • Subjects who have had active autoimmune diseases requiring systemic treatment in the past two years (such as use of disease-modifying drugs, corticosteroids, immunosuppressive therapy), and replacement therapy (such as thyroid hormone, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered systemic treatment.
  • Subjects with non-infectious pneumonia/interstitial lung disease (including radiation pneumonitis) requiring systemic glucocorticoid therapy that is currently uncontrolled.
  • Presence of brainstem, meningeal metastasis, spinal cord metastasis or compression.
  • Presence of active central nervous system (CNS) metastatic lesions. Note: Subjects with previously treated brain metastases (such as surgery or radiotherapy) are allowed to enroll if they are clinically stable for at least 2 weeks (from the time of first administration of study drug) and have discontinued corticosteroid hormones for 7 days before administration of study drug; untreated asymptomatic brain metastases (i.e., no neurological symptoms, no need for corticosteroid hormones, no brain metastases with a long axis >1.5 cm and no obvious peritumoral edema) are eligible to enroll.
  • Presence of pleural effusion, pericardial effusion or ascites with clinical symptoms or requiring repeated drainage.
  • Presence of uncontrolled comorbidities currently including but not limited to decompensated liver cirrhosis, nephrotic syndrome, uncontrolled metabolic disorders, or psychiatric/social conditions that would limit compliance with study requirements or affect the subject's ability to provide written informed consent.
  • History of myocarditis, cardiomyopathy or malignant arrhythmia. Unstable angina pectoris requiring hospitalization within 12 months before the first dose of study drug, myocardial infarction, congestive heart failure (New York Heart Association functional class II or higher), vascular disease (such as aortic aneurysm at risk of rupture), or other cardiac damage that may affect the safety evaluation of the study drug (such as poorly controlled arrhythmia or myocardial ischemia) within 12 months before the first dose of study drug.
  • Occurrence of any arterial thrombotic events within 6 months before the first dose of study drug; grade 3 or higher venous thromboembolic events according to NCI CTCAE 5.0; transient ischemic attacks; cerebrovascular accidents; hypertensive crises or hypertensive encephalopathy; exacerbation of chronic obstructive pulmonary disease within 1 month before the first dose of study drug; current hypertension with systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg despite oral antihypertensive therapy.
  • History of severe bleeding tendency or coagulation dysfunction; significant bleeding symptoms within 1 month before the first dose of study drug, including but not limited to gastrointestinal bleeding, bleeding peptic ulcer, hemoptysis (defined as coughing up or spitting out ≥1 teaspoon fresh blood or small clots or coughing up blood without sputum), which allows for inclusion if it is due to hemorrhoids and does not require intervention.
  • Active or past history of confirmed inflammatory bowel disease (such as Crohn's disease, ulcerative colitis, or chronic diarrhea).
  • Severe infection occurring within 4 weeks prior to the first dose of study drug, including but not limited to complications requiring hospitalization, sepsis, or severe pneumonia; active infection treated with systemic anti-infective therapy within 2 weeks prior to the first dose of study drug (excluding antiviral therapy for hepatitis B or C).
  • Known active tuberculosis (TB) or suspected active TB requiring clinical evaluation to rule out; known active syphilis infection.
  • Participants with active hepatitis B (HBsAg-positive with HBV-DNA levels above 1000 copies/mL (200 IU/mL) or higher than the lower limit of detection, whichever is higher) must receive antiviral therapy for hepatitis B during the study treatment period; active hepatitis C infection (HCV antibody-positive with HCV-RNA levels above the lower limit of detection).
  • History of immunodeficiency; positive HIV antibody test; current use of long-term systemic corticosteroids or other immunosuppressive agents.
  • Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
  • Unresolved toxicities from prior anti-tumor therapy, defined as toxicities not yet resolved to NCI CTCAE version 5.0 grade 0 or 1, or at a level dictated in the inclusion/exclusion criteria, with the exception of alopecia. Participants with irreversible toxicities that are not expected to be exacerbated by study drug may be included in the study after consultation with the investigator (e.g., hearing loss). Participants with radiation-induced long-term toxicities judged by the investigator to be irreversible may be included in the study.
  • Major surgery or serious injury within 30 days prior to the first dose of study drug, or planned major surgical procedure within 30 days after the first dose of study drug (at the discretion of the investigator); minor surgical procedure within 3 days prior to the first dose of study drug (excluding peripheral venous catheterization and placement of venous infusion port).
  • Known hypersensitivity to any component of the study drug; history of serious hypersensitivity reaction to other monoclonal antibodies.
  • Receipt of live vaccine or attenuated live vaccine within 30 days prior to the first dose of study drug, or planned receipt of live vaccine or attenuated live vaccine during the study period; use of inactivated vaccine is allowed.
  • Known history of psychiatric illness, drug abuse, alcoholism, or drug addiction.
  • Pregnant or breastfeeding women.
  • Any past or current disease, treatment, or laboratory abnormality that may confound the study results, interfere with subject participation for the full duration of the study, or may not be in the best interest of the subject to participate in the study.
  • Local or systemic diseases caused by non-malignant tumors; or diseases or symptoms secondary to malignancy that may result in higher medical risk and/or uncertainty in survival assessment, such as tumor leukemic reaction (white blood cell count >20×109/L), cachexia (known weight loss exceeding 10% in the 3 months prior to screening), etc.

Trial locations and contacts

1 site in 1 country.

Hong Shen, MD contact

+86 13857136137

shenhong0023@zju.edu.cn

Jing Zhao, MD contact

+86 13958122786

jingzhao@zju.edu.cn

China1 site, 1 recruiting

  • 2nd Affiliated Hospital, School of Medicine, Zhejiang University, China

    Hangzhou, Zhejiang, 310000

    Hong Shen, MD, +86 13857136137, shenhong0023@zju.edu.cn

    Hong Shen, MD

    Recruiting

Other trials in China

About this study

Official title: Cadonilimab Combined With Anlotinib in Locally Advanced or Relapsed/Metastatic Esophageal Squamous Cell Carcinoma Patients After Failure of PD-1 Inhibitor Combined With Platinum-containing Chemotherapy: A Single-center, Single-arm Exploratory Study

Advanced esophageal squamous cell carcinoma patients who have failed first-line PD-1 inhibitor combined with chemotherapy lack a standard treatment option. Second-line treatments have limited efficacy, indicating a significant unmet clinical need. Anlotinib is a novel multi-target tyrosine kinase inhibitor (TKI) has anti-tumor angiogenesis and tumor growth inhibition effects. Cadonilimab is a human immunoglobulin (Ig) G1 monoclonal antibody (mAb), which is a bispecific antibody that blocks both PD-1 and CTLA-4. Both of them have shown certain efficacy and good safety in more than second-line therapy for patients with advanced esophageal squamous cell carcinoma as monotherapy. This study aims to evaluate the efficacy and safety of cadonilimab combined with anlotinib in patients with locally advanced or recurrent/metastatic esophageal squamous cell carcinoma who have progressed on PD-1 inhibitor combined with platinum-containing chemotherapy.

Being tested
Cadonilimab combined Anlotinib
Keywords
Esophageal Squamous Cell Carcinoma, Cadonilimab, Anlotinib, CTLA-4, PD-1
Medical subject headings
Esophageal Squamous Cell Carcinoma, Diabetes Mellitus, Insulin-Dependent, 12

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Cadonilimab combined AnlotinibDrug

    Cadonilimab: intravenous administration at a dose of 10mg/kg on day 1 of each cycle, every 3 weeks (Q3W) Anlotinib: 12mg, orally once a day (orally before breakfast, the daily medication time should be as the same as possible), continuous taking for 2 weeks, stopping for 1 week, 3 weeks (21 days) as a treatment cycle

Study groups in NCT05990231
Study groupRoleWhat they receive
Cadonilimab combined with anlotinibExperimentalNot described
Receives: Drug: Cadonilimab combined Anlotinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective response rate

    The proportion of patients whose tumor volume reduced by 30% and could maintain for more than 4 weeks, that is, the sum of the proportion of complete remission (CR) and partial remission (PR)

    Measured: 2 years

Secondary outcomes (5)

  1. Disease control rate （DCR)

    The percentage of disease remission (including complete remission and partial remission, pr+cr) and stable disease (SD) in the number of evaluable cases after treatment

    Measured: 2 years

  2. Duration of Response(DOR)

    Remission duration refers to the time from the first CR or PR to disease progression.

    Measured: 2 years

  3. Progression-Free-Survival （PFS）

    Time from randomization to disease progression or death

    Measured: 2 years

  4. Overall survival (OS)

    The overall survival time of tumor patients

    Measured: 2 years

  5. Adverse events

    The incidence and severity of adverse events (AES) and clinically significant abnormal laboratory test results.

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Aug 2023
  2. Study start1 Sep 2023 (estimated)
  3. Primary completion1 Aug 2025 (estimated)
  4. Study completion1 Aug 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
35 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05990231
Sponsor's protocol ID
2023-0563
Status last verified
Aug 2023
First submitted
6 Aug 2023
Last updated
11 Sep 2023
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cadonilimab combined Anlotinib in people with Esophageal Squamous Cell Carcinoma, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 11 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Hong Shen, MD (+86 13857136137, shenhong0023@zju.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective response rate (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05990231.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Sep 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in