A Phase lb/lI Clinical Study in Advanced or Metastatic Esophageal Squamous Cell Carcinoma

NCT06487702 | Not Yet Recruiting Phase 2

• 1 other identifier: HMPL-013-FLAG-E102
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Esophageal Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (2)

• MTD and/or PR2D

  To determine the Maximum Tolerated Dose ( MTD) and/or PR2D of fruquintinib combined with Cadonilimab and Tegafur,Gimeracil and Oteracil Porassium in patients with Esophageal squamous cell carcinoma (Phase Ib)

  During the first 3 weeks

• 16-Week Progression-free Survival (PFS) Rate (Phase II)

  16-Week Progression-free survival (PFS) rate is defined as the percentage of patients who are progression-free (stable disease, partial response, or complete response as defined by RECIST v1.1 criteria) at 16 weeks post registration

  16 week

Secondary Outcomes (3)

• Overall Response Rate (ORR) (Phase Ib）

  Tumor assessment will be performed using radiography method every 6 weeks until the occurrence of progressive disease (PD), using RECIST v 1.1

• Disease control rate (DCR) (Phase Ib）

  from treatment up to progressive disease or EOT due to any cause up to 1 year

• Overall survival (OS) （Phase Ib)

  up to approximately 1 year

Study Arms (1)

Experimental:fruquintinib+Candonilimab + Tegafur，Gimeracil and Oteracil Potassium

EXPERIMENTAL

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

Drug: fruquintinib++Candonilimab+ Tegafur，Gimeracil and Oteracil Potassium

Interventions

fruquintinib++Candonilimab+ Tegafur，Gimeracil and Oteracil Potassium DRUG

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

Experimental:fruquintinib+Candonilimab + Tegafur，Gimeracil and Oteracil Potassium

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• age:18-75 years old, Male or female patients
• 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)
• Irretrievably resected, local advanced, relapsed or metastatic esophageal squamous cell carcinoma
• 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.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 to 1
• At least one measurable lesion (RECIST1.1)
• Life expectancy of more than 3 months;
• 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
• Have fully understood and voluntarily sign the ICF for this study;
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedure;
• Adequate hepatic, renal, heart, and hematologic functions

You may not qualify if:

• 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;
• 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
• 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
• Have symptomatic central nervous system metastases (with stable brain metastases confirmed by imageology for more than 3 months were eligible)
• 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;
• 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
• 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
• 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;
• Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation
• With thrombotic diseases or receiving anticoagulant drugs;
• Patients at risk of gastrointestinal hemorrhage or obstruction;
• Unable to swallow the experimental drug;
• 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;
• Patients with complications who require long-term use of immunosuppressive drugs or those who need systemic or local administration of corticosteroids with immunosuppressive effects

Sponsors & Collaborators

• Rui-hua Xu, MD, PhD: lead

Study Sites (1)

Medical Oncology,Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

potassium oxonate

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Central Study Contacts

Hua R Xu, MD

CONTACT

13922206676; xurh@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief physician

Study Record Dates

• First Submitted: June 13, 2024
• First Posted: July 5, 2024
• Study Start: July 10, 2024
• Primary Completion (Estimated): June 10, 2026
• Study Completion (Estimated): June 10, 2027
• Last Updated: July 5, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)