Trial Title:
Adebrelimab in Combination With Apatinib and Chemotherapy/Chemoradiotherapy in Immuno-experienced Second-line ESCC.
NCT ID:
NCT06464614
Condition:
Esophageal Cancer
Conditions: Official terms:
Paclitaxel
Apatinib
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:
Adebrelimab
Description:
Adebrelimab 1200mg，d1，q3w, until disease progression or unacceptable toxicity
Arm group label:
Adebrelimab＋Apatinib＋Investigator chosen chemotherapy (ICC)
Arm group label:
Adebrelimab＋Apatinib＋Radiotherapy＋Investigator chosen chemotherapy (ICC)
Other name:
SHR-1316
Intervention type:
Drug
Intervention name:
Apatinib
Description:
Apatinib 250mg，d1-21，q3w, until disease progression or unacceptable toxicity
Arm group label:
Adebrelimab＋Apatinib＋Investigator chosen chemotherapy (ICC)
Arm group label:
Adebrelimab＋Apatinib＋Radiotherapy＋Investigator chosen chemotherapy (ICC)
Other name:
Apatinib capsule
Intervention type:
Drug
Intervention name:
Investigator chosen chemotherapy (ICC)
Description:
Nab-paclitaxel: 125mg/m2 intravenously, D1, D8, q3w, 4-6 cycles;Intravenous infusion of
100 mg, D1, qw is used at the same time as radiotherapy.
Ilinotecan: 125mg/m2 intravenously, D1, D8, q3w, 4-6 cycles; Capecitabine, 625 mg/m2
orally, d1-14, q3w; continued until disease progression, intolerable toxicity, or
withdrawal due to other reasons; when synchronized with radiotherapy, 625mg/m2, bid,
oral, d1-5, qw.
Arm group label:
Adebrelimab＋Apatinib＋Investigator chosen chemotherapy (ICC)
Arm group label:
Adebrelimab＋Apatinib＋Radiotherapy＋Investigator chosen chemotherapy (ICC)
Other name:
Albumin-paclitaxel
Intervention type:
Radiation
Intervention name:
Radiotherapy
Description:
Radiotherapy mode: IMRT for the primary lesion and SBRT for the metastasis; If the
patient has symptoms of dysphagia, the radiation dose is 1.8 Gy×28 F or 2 Gy×25 F, d1-5 5
times a week; If oligometastatic lesions occur in the body: the radiation dose is 8
Gy×5F, d1-5; If oligometastatic lesions occur in the brain, the radiation dose is 7
Gy×5F, d1-5.
Arm group label:
Adebrelimab＋Apatinib＋Radiotherapy＋Investigator chosen chemotherapy (ICC)
Summary:
To assess the efficacy and safety of adebrelimab in combination with apatinib mesylate
and chemoradiotherapy in immuno-experienced second-line esophageal squamous cell
carcinoma (with symptomatic dysphagia or oligometastatic disease)，and to evaluate the
efficacy and safety of adebrelimab in combination with apatinib mesylate and
chemoradiotherapy in immuno-experienced second-line esophageal squamous cell carcinoma
(without symptomatic dysphagia or oligometastatic disease).
Detailed description:
The treatment of advanced second-line esophageal squamous cell carcinoma has always been
mainly chemotherapy. Since 2019, a number of phase III clinical trials (ESCORT,
KEYNOTE-181, RATIONALE 302, ATRACTION-3, etc.) have confirmed that there is a significant
difference in OS between the immune monotherapy group and the chemotherapy group, and
immunotherapy can bring better survival benefits. Although the above studies have brought
new possibilities for second-line patients with advanced esophageal cancer, the results
of the study show that the response rate of immune monotherapy is limited, with a
single-agent ORR of about 13%-20%, mPFS of about 2 months, and mOS about 8 months.
Therefore, finding a suitable combination therapy model to further improve the efficacy
of advanced second-line esophageal cancer has gradually become a research hotspot in
recent years. In recent years, many experts have also made a lot of explorations. The
combination of anti-angiogenic drugs and immunotherapy drugs can be synergistic.
Dysphagia is a major symptom in patients with esophageal cancer, leading to significant
nutritional deficiencies, pain, and subsequent deterioration in quality of life.
Management of dysphagia is a key goal of esophageal cancer treatment, along with the need
to improve nutritional status and quality of life, which may have a positive impact on
the overall prognosis of patients. Current treatment methods for dysphagia include
esophageal dilation, endoluminal stenting, systemic chemotherapy, external beam
radiotherapy (EBRT), brachytherapy, and concurrent chemoradiotherapy (CTRT). At present,
there is no consensus on how to better manage this symptom with these treatment regimens,
and more research is needed to continue to explore.
To assess the efficacy and safety of adebrelimab in combination with apatinib mesylate
and chemoradiotherapy in immuno-experienced second-line esophageal squamous cell
carcinoma (with symptomatic dysphagia or oligometastatic disease), and to evaluate the
efficacy and safety of adebrelimab in combination with apatinib mesylate and
chemoradiotherapy in immuno-experienced second-line esophageal squamous cell carcinoma
(without symptomatic dysphagia or oligometastatic disease).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
-
1. Age 18-75 years old, male or female; 2. Esophageal squamous cell carcinoma
confirmed by histology or cytology; 3. Patients who have progressed or are
intolerant to first-line chemotherapy combined with immunotherapy (chemotherapy
regimen can include platinum, purple shirt or fluorouracil as the basis, etc.)
(progression of maintenance therapy after first-line chemotherapy combined with
immunization can also be included).
4. Cohort A: Subjects who have at least one of the following two conditions will
be treated with adebelimab combined with apatinib mesylate and
chemoradiotherapy;
1. Symptomatic dysphagia, Mellow score ≥1 (Mellow score: 0 = able to eat all solid
foods, 1 = only partially solid foods, 2 = able to eat soft foods, 3 = only
able to drink liquids, 4 = complete dysphagia);
2. Hypometastatic disease: Oligometastatic disease is considered when there are ≤
3 metastases in the liver, lungs, retroperitoneal lymph nodes, adrenal glands,
soft tissues, bones, or brain. In addition, after receiving a median of 18
weeks of systemic therapy, metastatic lesions are considered to be
oligometastatic lesions at the time of restaging if they do not progress or
only progress in size. If the number of lesions increases when restaged after
systemic therapy, it is not considered oligometastatic disease.
Cohort B: If the subjects do not have the above conditions, they will be
treated with adebelimab in combination with apatinib mesylate and chemotherapy;
5. Have at least one measurable lesion according to the Efficacy Evaluation
Criteria in Solid Tumors (RECIST 1.1); 6.ECOG：0～1； 7. Expected survival≥12
weeks; 8. The blood routine and biochemical indexes of the subjects within 7
days before enrollment meet the following criteria:
a. Hemoglobin ≥90g/L, absolute neutrophil count (ANC) ≥ 1.5×109/L, platelet ≥
100×109/L (patients must not have received blood transfusion or growth factor
support within 14 days of blood sample collection); b. ALT, AST ≤ 2.5 times the
upper limit of normal (ULN); ALP ≤ 2.5 times ULN; c. Serum total bilirubin <
1.5 times ULN (patients with Gilbert syndrome can be enrolled if total
bilirubin < 3 times ULN); d. Serum creatinine < 1.5 times ULN or estimated
glomerular filtration rate ≥60ml/min/1.73m2; e. Serum albumin≥30g/L;
International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times ULN,
unless the patient is receiving anticoagulant therapy and the PT value is
within the range of anticoagulant intended treatment; Activated partial
thromboplastin time (APTT) ≤ 1.5 times ULN. 9. Doppler ultrasound assessment:
left ventricular ejection fraction (LVEF) ≥ low limit of normal (50%).
10. Females of childbearing potential should agree to use contraception (such as
intrauterine device, contraceptive pills or condoms) during the study and for 6
months after the end of the study, have a negative serum or urine pregnancy
test within 7 days prior to study enrollment and must be non-lactating
patients, and males should agree to use contraception during the study and for
6 months after the end of the study period; 11. No serious concomitant disease
that makes the survival time < 5 years; 12. Subjects voluntarily joined this
study, signed the informed consent form, had good compliance, and cooperated
with follow-up.
Exclusion Criteria:
-
1. Patients have any active autoimmune disease or history of autoimmune disease
(such as the following, but not limited to: autoimmune hepatitis, interstitial
pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis,
hyperthyroidism; patients with vitiligo; asthma that has been completely
relieved in childhood and does not require any intervention in adulthood can be
included; asthma patients requiring medical intervention with bronchodilators
cannot be included); 2. The patient is using immunosuppressants, or systemic
hormone therapy to achieve the goal of immunosuppression (dose> 10mg/day
prednisone or other effective hormones), and continues to use it within 2 weeks
before enrollment; 3. Patients with esophageal squamous cell carcinoma whose
primary lesion is active hemorrhage; 4. Those with a variety of factors that
affect oral medication (such as inability to swallow, gastrointestinal
resection, chronic diarrhea and intestinal obstruction, etc.); 5. Patients with
brain metastases with symptoms or symptomatic control time of less than 3
months; 6. Patients with any severe/uncontrolled disease, including: patients
with unsatisfactory blood pressure control (systolic blood pressure ≥150mmHg or
diastolic blood pressure ≥100 mmHg); Patients with grade I or grade myocardial
ischemia or myocardial infarction, arrhythmias (including QT interval ≥480ms)
and grade I cardiac insufficiency, active or uncontrolled serious infections,
liver disease such as decompensated liver disease, active hepatitis B (HBV-DNA≥
104 copies/ml or 2000IU/ ml) or hepatitis C (positive for hepatitis C antibody
and HCV-RNA above the lower limit of detection of the analytical method),
urinalysis shows urine protein ≥++, and 24-hour urine protein quantification
>1.0g; 7. Long-term unhealed wounds or fractures; 8. Pulmonary hemorrhage with
NCI CTCAE grade >1 within 4 weeks prior to enrollment; bleeding from other
sites with NCI CTCAE grade >2 within 4 weeks prior to enrollment; patients with
bleeding tendencies (such as active peptic ulcers) or patients who are
receiving thrombolytic or anticoagulant therapy such as warfarin, heparin, or
their analogues; 9. Patients who have had arterior/venous thrombotic events
within 6 months, such as cerebrovascular accident (including transient ischemic
attack), deep vein thrombosis and pulmonary embolism; 10. Patients whose
imaging shows that the tumor has invaded important blood vessels or who are
judged by the investigator to have a high probability of invading important
blood vessels during the follow-up study period, causing fatal hemorrhage; 11.
Pregnant or lactating women; 12. Patients with other malignant tumors within 5
years (except for basal cell carcinoma of the skin and carcinoma in situ of the
cervix that have been cured); 13. Patients with a history of psychotropic drug
abuse who cannot be abstained from or patients with mental disorders; 14.
Patients who have participated in clinical trials of other drugs within four
weeks; 15. According to the judgment of the investigator, patients with
concomitant diseases that seriously endanger the safety of patients or affect
the completion of the study; 16. Those who, in the opinion of the investigator,
are not suitable for inclusion.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
The First Affiliated Hospital of Henan University of Science and Technology
Address:
City:
Luoyang
Zip:
470000
Country:
China
Start date:
July 15, 2024
Completion date:
August 1, 2026
Lead sponsor:
Agency:
The First Affiliated Hospital of Henan University of Science and Technology
Agency class:
Other
Source:
The First Affiliated Hospital of Henan University of Science and Technology
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06464614
