Recurrent or Metastatic Esophageal Squamous Cell CarcinomaPhase 2NCT05732662
SBRT Combined With AK104 to Treatment Relapsed or Metastatic ESCC
A Phase 2 study testing SBRT and Cadonilimab in people with Recurrent or Metastatic Esophageal Squamous Cell Carcinoma, run by The First People's Hospital of Changzhou.
Trial summary
The entire treatment process is divided into two phases: Phase I SBRT combined with PD-1/CTLA-4 bispecific antibody (AK104) and Phase II AK104 single-agent maintenance therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent or Metastatic Esophageal Squamous Cell Carcinoma
- What is being tested?
- SBRT and Cadonilimab
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- No sites listed yet
- Study dates
- Apr 2023to Dec 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. age ≥ 18 years. 2. patients enrolled must be eligible for PD-1 treatment-naïve patients with recurrent or metastatic advanced esophageal squamous carcinoma with definite measurable recurrent or metastatic lesions.
- 3. have at least 2 or more clearly measurable lesions (maximum diameter of lesions≥1 cm and shortest diameter of ≥1.5 cm of lymph nodes according to RECIST v1.1), at least one of which is feasible for radiation therapy).
- 4. no congestive heart failure, unstable angina, or unstable arrhythmia within the last 6 months.
- 5. patient activity status score of 0-3 on the Eastern Cooperative Oncology Group (ECOG) scale with a life expectancy assessment of ≥ 3 months.
- 6. no previous serious abnormalities of hematopoietic, cardiac, pulmonary, hepatic, or renal function and immunodeficiency.
- 7. absolute T-lymphocyte values ≥ 0.5 times the lower limit of normal and neutrophils ≥ 2.0 × 109/L; AST and ALT ≤ 3.0 times the upper limit of normal (≤ 5.0 times the upper limit of normal for hepatocellular carcinoma/metastatic liver cancer); and creatinine ≤ 3.0 times the upper limit of normal, 1 week before enrollment.
- 8. patients must have the ability to understand and voluntarily sign the informed consent form.
Who cannot join
- 1. pregnant gestational or lactating women. 2. those with a history of other malignant diseases in the last 5 years. 3. persons with a history of uncontrolled epilepsy, central nervous system disease, or psychiatric disorder whose clinical severity, as judged by the investigator, may prevent signing an informed consent form or affect patient compliance with medication.
- 4. clinically significant (i.e., active) heart disease such as symptomatic coronary artery disease, New York Heart Association (NYHA) class II or worse congestive heart failure or severe arrhythmias requiring pharmacologic intervention, or a history of myocardial infarction within the last 12 months.
- 5. organ transplantation requiring immunosuppressive therapy. 6. Significant active infection or, in the judgment of the investigator, significant hematologic, renal, metabolic, gastrointestinal, endocrine dysfunction or metabolic disorder, or other serious uncontrolled concomitant disease.
- 7. hypersensitivity to any investigational drug component. 8. have a history of immunodeficiency, including testing positive for HIV or having other acquired or congenital immunodeficiency diseases, or a history of organ transplantation, or other immune-related diseases requiring long-term oral hormone therapy.
- 9. those who are undergoing acute or chronic TB infection (patients with positive T-spot test and suspicious TB foci on chest radiograph).
- 10. other conditions that the investigator considers unsuitable for enrollment.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: SBRT Combined With PD-1/CTLA-4 Dual Antibody to Overcome Anti-PD-1 Resistant in Relapsed or Metastatic Esophageal Squamous Cell Carcinoma
The entire treatment process is divided into two phases: Phase I SBRT combined with PD-1/CTLA-4 bispecific antibody (AK104) and Phase II AK104 single-agent maintenance therapy.
Read the detailed description
Phase I SBRT combined with AK104 treatment Target area and dose of SBRT: Select a relapsed or metastatic lymph node or lesion that has little effect on surrounding normal tissues and has not been irradiated before, and then perform radiation therapy with a total dose of 24-50Gy/8-12.5Gy/3-4f per lesion (the specific target area and dose range will be decided by the treating physician). AK104 is administered within one week after SBRT, and the regimen for AK104 is 10 mg/kg as a single dose. If multiple target lesions are treated with SBRT, multiple cycles of 21 days each are possible. When patients are treated with multiple courses of radiotherapy, it is difficult to ensure the accuracy of the overlapping doses of the re-course of radiotherapy, and the cumulative dose of organs at risk (OAR) is evaluated using the deformable image registration (DIR) technique.
Phase II AK104 monotherapy maintenance phase Monotherapy maintenance with AK104 10 mg/kg every 21 days until progression, up to one year if no progression. Patients were enrolled in Phase I and Phase II for a minimum of three cycles.
In addition, 10 mL of peripheral blood was drawn from patients before each cycle of treatment and analyzed by flow cytometry for lymphocyte subpopulation. And the changes of HMGB1 and cytokines IL-8, IL-6, IL-12, IFN-α, IFN-β, IL-2, IL-4, IL-5, INF-γ, TNF-α, IL-10, TGF-β were detected by ELISA test. By testing the above indicators, they are used to respond to the immune status after treatment as well as to screen for valid indicators that can be used to assess efficacy.
Throughout the study period, the assessment should be performed as much as possible according to the imaging assessment plan time points specified in the protocol. Tumor imaging assessments will be performed every 6 weeks during the first phase of treatment and every 9 weeks during the second phase of treatment. This project used velosity software to perform clinical tumor imaging assessment according to RECIST 1.1 criteria and irRECIST and iRECIST criteria assessment every 6 weeks; NCI-CTCAE 5.0 was used for safety assessment and adverse events were recorded throughout the study until 30 days after the end of treatment.
After the end of treatment, all subjects will be followed for survival every 3 months until death, loss to follow-up, withdrawal of knowledge, or the sponsor's decision to terminate the study.
- Being tested
- SBRT, Cadonilimab
- Keywords
- SBRT, AK104
- Medical subject headings
- Recurrence, Esophageal Squamous Cell Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SBRTRadiation
24-50Gy/8-12.5Gy/3-4f
CadonilimabDrug
10 mg/kg,q3w
| Study group | Role | What they receive |
|---|---|---|
| SBRT combined with PD-1/CTLA-4 dual antibody | Experimental | Not described Receives: Radiation: SBRT; Drug: Cadonilimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
ORR
objective response rate
Measured: Up to 3 years
Secondary outcomes (3)
PFS
progression-free surviva
Measured: Up to 3 years
OS
Overall survival
Measured: Up to 3 years
Treatment Related Severe Adverse Effects
Number of participants with treatment-related severe adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Measured: Up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2023
- Study startApr 2023 (estimated)
- Primary completionDec 2025 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent or Metastatic Esophageal Squamous Cell CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The First People's Hospital of Changzhou
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Wendong Gu, The First People's Hospital of Changzhou
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05732662
- Sponsor's protocol ID
- SBRTAK104
- Status last verified
- Feb 2023
- First submitted
- 8 Feb 2023
- Last updated
- 17 Feb 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- SBRT Combined With PD-1/CTLA-4 Dual Antibody to Overcome Anti-PD-1 Resistant in Relapsed or Metastatic Esophageal Squamous Cell Carcinoma
- ClinicalTrials.gov ID
- NCT05732662
- Acronym / sponsor ID
- SBRTAK104
- Keywords
- SBRT, AK104
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- The First People's Hospital of ChangzhouUniversity, hospital or other
- Study start
- Apr 2023 (estimated)
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 17 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The entire treatment process is divided into two phases: Phase I SBRT combined with PD-1/CTLA-4 bispecific antibody (AK104) and Phase II AK104 single-agent maintenance therapy.
Detailed description
Phase I SBRT combined with AK104 treatment Target area and dose of SBRT: Select a relapsed or metastatic lymph node or lesion that has little effect on surrounding normal tissues and has not been irradiated before, and then perform radiation therapy with a total dose of 24-50Gy/8-12.5Gy/3-4f per lesion (the specific target area and dose range will be decided by the treating physician). AK104 is administered within one week after SBRT, and the regimen for AK104 is 10 mg/kg as a single dose. If multiple target lesions are treated with SBRT, multiple cycles of 21 days each are possible. When patients are treated with multiple courses of radiotherapy, it is difficult to ensure the accuracy of the overlapping doses of the re-course of radiotherapy, and the cumulative dose of organs at risk (OAR) is evaluated using the deformable image registration (DIR) technique.
Phase II AK104 monotherapy maintenance phase Monotherapy maintenance with AK104 10 mg/kg every 21 days until progression, up to one year if no progression. Patients were enrolled in Phase I and Phase II for a minimum of three cycles.
In addition, 10 mL of peripheral blood was drawn from patients before each cycle of treatment and analyzed by flow cytometry for lymphocyte subpopulation. And the changes of HMGB1 and cytokines IL-8, IL-6, IL-12, IFN-α, IFN-β, IL-2, IL-4, IL-5, INF-γ, TNF-α, IL-10, TGF-β were detected by ELISA test. By testing the above indicators, they are used to respond to the immune status after treatment as well as to screen for valid indicators that can be used to assess efficacy.
Throughout the study period, the assessment should be performed as much as possible according to the imaging assessment plan time points specified in the protocol. Tumor imaging assessments will be performed every 6 weeks during the first phase of treatment and every 9 weeks during the second phase of treatment. This project used velosity software to perform clinical tumor imaging assessment according to RECIST 1.1 criteria and irRECIST and iRECIST criteria assessment every 6 weeks; NCI-CTCAE 5.0 was used for safety assessment and adverse events were recorded throughout the study until 30 days after the end of treatment.
After the end of treatment, all subjects will be followed for survival every 3 months until death, loss to follow-up, withdrawal of knowledge, or the sponsor's decision to terminate the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| SBRT combined with PD-1/CTLA-4 dual antibody | Experimental | Radiation: SBRT, Drug: Cadonilimab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 1. age ≥ 18 years. 2. patients enrolled must be eligible for PD-1 treatment-naïve patients with recurrent or metastatic advanced esophageal squamous carcinoma with definite measurable recurrent or metastatic lesions.
- 3. have at least 2 or more clearly measurable lesions (maximum diameter of lesions≥1 cm and shortest diameter of ≥1.5 cm of lymph nodes according to RECIST v1.1), at least one of which is feasible for radiation therapy).
- 4. no congestive heart failure, unstable angina, or unstable arrhythmia within the last 6 months.
- 5. patient activity status score of 0-3 on the Eastern Cooperative Oncology Group (ECOG) scale with a life expectancy assessment of ≥ 3 months.
- 6. no previous serious abnormalities of hematopoietic, cardiac, pulmonary, hepatic, or renal function and immunodeficiency.
Key exclusion criteria (6 listed)
- 1. pregnant gestational or lactating women. 2. those with a history of other malignant diseases in the last 5 years. 3. persons with a history of uncontrolled epilepsy, central nervous system disease, or psychiatric disorder whose clinical severity, as judged by the investigator, may prevent signing an informed consent form or affect patient compliance with medication.
- 4. clinically significant (i.e., active) heart disease such as symptomatic coronary artery disease, New York Heart Association (NYHA) class II or worse congestive heart failure or severe arrhythmias requiring pharmacologic intervention, or a history of myocardial infarction within the last 12 months.
- 5. organ transplantation requiring immunosuppressive therapy. 6. Significant active infection or, in the judgment of the investigator, significant hematologic, renal, metabolic, gastrointestinal, endocrine dysfunction or metabolic disorder, or other serious uncontrolled concomitant disease.
- 7. hypersensitivity to any investigational drug component. 8. have a history of immunodeficiency, including testing positive for HIV or having other acquired or congenital immunodeficiency diseases, or a history of organ transplantation, or other immune-related diseases requiring long-term oral hormone therapy.
- 9. those who are undergoing acute or chronic TB infection (patients with positive T-spot test and suspicious TB foci on chest radiograph).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SBRT24-50Gy/8-12.5Gy/3-4f | Radiation | SBRT combined with PD-1/CTLA-4 dual antibody |
| Cadonilimab10 mg/kg,q3w | Drug | SBRT combined with PD-1/CTLA-4 dual antibody |
Primary outcome
ORR
Time frame: Up to 3 years
objective response rate
3 secondary outcomes
PFS
Time frame: Up to 3 years
OS
Time frame: Up to 3 years
Treatment Related Severe Adverse Effects
Time frame: Up to 3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing SBRT and Cadonilimab in people with Recurrent or Metastatic Esophageal Squamous Cell Carcinoma, run by The First People's Hospital of Changzhou.
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 7 inclusion and 6 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: opening soon, as of the sponsor's last update on 17 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Wendong Gu, Doctor (13861220022 ext. 0519-68871162, guwendong1415@czfph.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ORR (time frame: Up to 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 17 Feb 2023.