Trial Title:
A Phase lb/lI Clinical Study in Advanced or Metastatic Esophageal Squamous Cell Carcinoma
NCT ID:
NCT06487702
Condition:
Esophageal Squamous Cell Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Esophageal Squamous Cell Carcinoma
Tegafur
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
fruquintinib++Candonilimab+ Tegafur，Gimeracil and Oteracil Potassium
Description:
Fruquintinib administration for 2 weeks followed by 1-week break
Candonilimab：10 mg/kg，D1，Q3W；
Tegafur，Gimeracil and Oteracil Potassium：30mg BID for body surface area < 1.25 m2; 40mg
BID for body surface area of 1.25-1.5 m2; and 50mg BID for body surface area >1.5 m2;
D1-14, q3w
Arm group label:
Experimental:fruquintinib+Candonilimab + Tegafur，Gimeracil and Oteracil Potassium
Summary:
This is a prospective, single-arm, open-label，multi-center, phase Ib/II study, aiming to
evaluate the efficacy and safety of Fruquintinib combined With Cadonilimab (AK104) and
Tegafur，Gimeracil and Oteracil Potassium in patients with locally advanced or metastatic
esophageal squamous cell carcinoma after the failure of first-line treatments.
Detailed description:
Esophageal cancer is a malignant tumor with high incidence and death rate in the world,
especially in china, and Esophageal squamous cell carcinoma (ESCC) is the main
pathological type of esophageal carcinoma in China. Among patients with advanced or
metastatic esophageal squamous cell carcinoma, the addition of immunotherapy to
chemotherapy, compared with chemotherapy, significantly improved overall survival and
progression-free survival in first-line treatments. Treatment of recurrent or metastatic
esophageal squamous cell carcinoma is usually poor. New treatments were
needed.Fruquintinib is an orally antiangiogenic agents, which target VEGFR1/2/3.
Candonilimab (AK104) is a PD-1/CTLA-4 Bispecific Antibody. A combination of Fruquintinib
and Candonilimab (AK104) and s-1 for advanced or metastatic esophageal squamous cell
carcinoma could be a novel therapy. Therefore, investigators initialize this phase Ib/II
study to explore the efficacy and safety of fruquintinib in combination with Candonilimab
(AK104) and S-1 treatment in ESCC patients with after failure in 1st-line treatment.
In dose escalation period, 3-12 patients with Esophageal squamous cell carcinoma will be
enrolled. Patients meeting enrollment eligibility will receive 21-day cycles of
fruquintinib 2-3 mg qd，D1-14,Q3W； combined with Candonilimab 10 mg/kg，D1，Q3W and S-1
(30mg BID for body surface area <1.25 m2;40mg BID for body surface area ≥1.25 - <1.5
m2;50mg BID for body surface area ≥1.5m2 ；D1-14,Q3W)
Safety information will be collected till disease progression or intolerable toxicity to
determine MTD and/or RPTD of fruquintinib combined with Candonilimab and S-1 in patients
with Esophageal squamous cell carcinoma .
This period will include the following 2 dose groups from low to high:
A: Fruquintinib 2 mg qd for 2 weeks followed by 1-week break + Candonilimab 10
mg/kg，intravenous infusion，D1, every 3 weeks+ S-1 ,Calculate dosage based on body surface
,30mg for BSA <1.25 m2;40 mg for BSA ≥1.25 - <1.5 m2; 50mg for BSA ≥1.5m2;BID，D1-14，Q3W
B: Fruquintinib 3 mg qd for 2 weeks followed by 1-week break + Candonilimab 10
mg/kg，intravenous infusion，D1, every 3 weeks+ S-1 ,Calculate dosage based on body surface
,30mg for BSA <1.25 m2;40 mg for BSA ≥1.25 - <1.5 m2; 50mg for BSA ≥1.5m2;BID，D1-14，Q3W
This study will use traditional 3+3 trial design (3 subjects will be enrolled in each
dose group first).
If 1 case of DLT is observed, additional 3 subjects will be enrolled in the same dose
group,when no new DLTs occurred, the trial was continued to the next dose level to
further evaluate toxicity ,to observe DLT and evaluate MTD.
If there are 2 or more cases of DLT in one dose group, the group lower than this dose
group by one level is MTD dose group. If 2 dose group levels MTD was not reached, then
the B group dose was RP2D.(DLT was predefined by the investigator in the protocol)
Subjects in the original dose group will continue to receive the next cycle of treatment
at the original dose till disease progression or treatment withdrawal due to any of the
following reasons: 1) death, 2) intolerable toxicity, 3) pregnancy, 4) the investigator
considers the study should be terminated for the subject's best interests, 5) the subject
or legal representative requests withdrawal, 6) loss to follow-up, 7) the subject has
poor compliance and cannot comply with the study protocol.
In phase II period,patients meeting enrollment eligibility will receive Fruquintinib PR2D
in combination with Candonilimab 10 mg/kg，intravenous infusion，D1, every 3 weeks and S-1
,Calculate dosage based on body surface ,30mg for BSA <1.25 m2;40 mg for BSA ≥1.25 - <1.5
m2; 50mg for BSA ≥1.5m2;BID，D1-14，Q3W, till disease progression or treatment withdrawal
due to any of the following reasons: 1) death, 2) intolerable toxicity, 3) pregnancy, 4)
the investigator considers the study should be terminated for the subject's best
interests, 5) the subject or legal representative requests withdrawal, 6) loss to
follow-up, 7) the subject has poor compliance and cannot comply with the study protocol.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. age:18-75 years old, Male or female patients
2. Histologically or cytologically confirmed esophageal squamous cell carcinoma
(including the gastroesophageal junction), (Adenosquamous carcinoma with squamous
cell carcinoma components-based is allowed to be included)
3. Irretrievably resected, local advanced, relapsed or metastatic esophageal squamous
cell carcinoma
4. Previously received platinum-based systemic anti-tumor first-line therapy; Or
received Neoadjuvant, adjuvant therapy, or radical chemoradiotherapy for ESCC, but
disease recurrence or progression within 6 months after completion of treatment; no
restrictions on prior immunotherapy treatment choice.
5. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 to 1
6. At least one measurable lesion (RECIST1.1)
7. Life expectancy of more than 3 months;
8. Women of childbearing age were required to have had a negative pregnancy test (serum
or urine) within 14 days before enrollment and to voluntarily use an appropriate
method of contraception during the observation period and for 8 weeks after the last
dose of the study drug.For men, either surgical sterilization or consent to use an
appropriate method of contraception during the observation period and for 8 weeks
after the last dose of the study drug was given
9. Have fully understood and voluntarily sign the ICF for this study;
10. Willingness and ability to comply with scheduled visits, treatment plans, laboratory
tests, and other study procedure;
11. Adequate hepatic, renal, heart, and hematologic functions
Exclusion Criteria:
1. Have had other malignancies within the past 5 years, except for curatively treated
radical skin basal cell or squamous cell carcinoma, Or cervical carcinoma in situ;
2. Have received major surgical procedures (such as craniotomy, thoracotomy, or
laparotomy) within 4 weeks before enrollment or are excepted to uddergo major
surgery during the study treatment; received laparoscopic exploration within 2 weeks
before enrollment; received central venous catheterization within 7 days prior to
enrollment
3. Have received chemotherapy, targeted therapy, traditional Chinese herbal medicine
with anti-tumor indications or immunomodulatory drugs (including thymosin,
interferon, interleukins, etc.) within the first 4 weeks prior to enrollment, or are
still within 5 half-lives of such medications
4. Have symptomatic central nervous system metastases (with stable brain metastases
confirmed by imageology for more than 3 months were eligible)
5. Severe infection ((≥CTCAE grade 2 infection) occurred within 4 weeks before the
first dose of study drug, such as severe pneumonia requiring hospitalization,
bacteremia, and infectious complications;Baseline chest imaging suggested active
pulmonary inflammation with clinically relevant symptoms or signs;the presence of
signs and symptoms of infection within 2 weeks before the first dose of the study
drug ,or the need for treatment with oral or intravenous antibiotics was excluded if
prophylactic antibiotics were used;
6. Previous and current presence of interstitial pneumonia, pneumoconiosis,
drug-related pneumonia, and severely impaired pulmonary function may interfere with
the detection and management of suspected drug-related pulmonary toxicity in
subjects;Subjects with radiation pneumonitis within 6 months
7. Had active pulmonary tuberculosis by medical history or CT examination, or who had a
history of active pulmonary tuberculosis within 1 year before enrollment ,or who had
a history of active pulmonary tuberculosis more than 1 year before enrollment but
had not received regular treatment
8. Congenital or acquired immune deficiency, such as human immunodeficiency virus (HIV)
infection, active hepatitis B (HBV DNA ≥ 500 IU/ml), hepatitis C (hepatitis C
antibody positive, and HCV-RNA above the detection limit of the assay) or
co-infection with hepatitis B and C;
9. Known history of allogeneic organ transplantation or allogeneic hematopoietic stem
cell transplantation
10. With thrombotic diseases or receiving anticoagulant drugs;
11. Patients at risk of gastrointestinal hemorrhage or obstruction;
12. Unable to swallow the experimental drug;
13. Patients who have previously experienced immune-related myocarditis, pneumonitis,
colitis, hepatitis, nephritis, etc.were judged to be at greater risk for
immunotherapy retreatment by the investigator;
14. Patients with complications who require long-term use of immunosuppressive drugs or
those who need systemic or local administration of corticosteroids with
immunosuppressive effects
15. Patients considered unsuitable for inclusion in this study by the investigator
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Medical Oncology,Sun Yat-sen University Cancer Center
Address:
City:
Guangzhou
Zip:
510060
Country:
China
Start date:
July 10, 2024
Completion date:
June 10, 2027
Lead sponsor:
Agency:
Rui-hua Xu, MD, PhD
Agency class:
Other
Source:
Sun Yat-sen University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06487702
