Anlotinib Plus Chemotherapy as First-line Therapy for Gastrointestinal Tumor Patients With Unresectable Liver Metastasis (ALTER-G-001)

NCT05262335 | Unknown Phase 2

• 1 other identifier: 2021223
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 7

Brief Summary

This is an open, multi-cohort, multi-center, exploratory and phase II clinical trial. To evaluate the efficacy and safety Anlotinib combined with chemotherapy as first-line and maintenance therapy for Gastrointestinal Tumors with Unresectable Liver Metastases.

Conditions

Gastrointestinal Tumors

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  Objective response rate is defined as the percentage of subjects whose best response was complete response (CR) or partial response (PR) according to the RECIST v1.1.

  up to 24 months

Secondary Outcomes (6)

• Progression-free survival (PFS)

  up to 24 months

• Disease Control Rate (DCR)

  up to 24 months

• Duration of Response (DoR)

  up to 24 months

• Safety: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

  Until 30 day safety follow-up visit

• Overall Survival (OS)

  Up to 24 months

Study Arms (3)

Experimental: Experimental group 1

EXPERIMENTAL

Initial treatment: Anlotinib + Oxaliplatin + Capecitabine. Maintenance treatment (after 6 cycles): Anlotinib + Capecitabine

Drug: Anlotinib + Oxaliplatin + Capecitabine

Experimental: Experimental group 2

EXPERIMENTAL

Initial treatment: Anlotinib + Cisplatin + Paclitaxel/ Docetaxel. Maintenance treatment (after 6 cycles): Anlotinib + Capecitabine

Drug: Anlotinib + Cisplatin + Paclitaxel/ Docetaxel

Experimental: Experimental group 3

EXPERIMENTAL

Initial treatment: Anlotinib + Standard first-line chemotherapy Maintenance treatment (after 6 cycles): Anlotinib + Capecitabine

Drug: Anlotinib + Standard first-line chemotherapy

Interventions

Anlotinib + Oxaliplatin + Capecitabine DRUG

1. Before 6 cycles, Anlotinib 12mg, po.qd, d1-14; Capecitabine 850 mg/m2, po. bid, d1-14; Oxaliplatin 130 mg/m2, iv (D1). The above schemes are repeated every three weeks. 2. After 6 cycles, the regimen is changed to Anlotinib (12mg, po.qd, d1-14)+ Capecitabine (500 mg, po. bid, d1-21). The regimen is repeated every 3 weeks until the disease progresses or unacceptable toxicity.

Experimental: Experimental group 1

Anlotinib + Cisplatin + Paclitaxel/ Docetaxel DRUG

1. Anlotinib 12mg, po.qd, d1-14; Cisplatin 60-75mg/m2, iv, d1/d1-d3; Paclitaxel 135mg/m2, iv (D1). or Docetaxel 75mg/m2, iv (D1). The above schemes are repeated every three weeks. 2. After 6 cycles, the regimen is changed to Anlotinib (12mg, po.qd, d1-14)+ Capecitabine (500 mg, po. bid, d1-21). The regimen is repeated every 3 weeks until the disease progresses or unacceptable toxicity.

Experimental: Experimental group 2

Anlotinib + Standard first-line chemotherapy DRUG

1. Anlotinib 12mg, po.qd, d1-14; Standard first-line chemotherapy determined by the researchers. The above schemes are repeated every three weeks. 2. After 6 cycles, the regimen is changed to Anlotinib (12mg, po.qd, d1-14)+ Capecitabine (500 mg, po. bid, d1-21). The regimen is repeated every 3 weeks until the disease progresses or unacceptable toxicity.

Experimental: Experimental group 3

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed Ⅳ phase of colorectal cancer with liver metastases (TanyNanyM1), and the liver metastases are unresectable; Or Histologically or cytologically confirmed Ⅳb phase of esophageal squamous cell carcinoma with liver metastases (TanyNanyM1) (excluding mixed type adenosquamous carcinoma), and the liver metastases are unresectable; Or Histologically or cytologically confirmed other gastrointestinal tumors with liver metastases (excluding gastrointestinal stromal tumors, neuroendocrine tumors and other malignant tumors of non-glandular epithelial origin), and the liver metastases are unresectable;
• No previous systemic treatment, including chemotherapy, targeted and immunotherapy;
• The target lesion must contain liver metastases. According to RECIST version 1.1, liver metastases have at least one measurable focus;
• Age from 18-75 years old;
• ECOG performance status of 0-1;
• Life expectancy of at least 3 months;
• The main organs are functioning normally (normal main organs function as defined below: Hemoglobin (Hb) ≥ 90 g/L, Neutrophils (ANC) ≥ 1.5×109/L, Platelet count (PLT) ≥ 90×109/L, Total bilirubin (TBIL) ≤ 1.5 × normal upper limit (ULN), Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 5 ×ULN, Creatinine Clearance rate (CCr) ≥60ml/min)
• Women of childbearing potential should agree to use and utilize an adequate method of contraception (such as intrauterine device，contraceptive and condom) throughout treatment and for at least 3 months after study is stopped；the result of serum or urine pregnancy test should be negative before enrollment；Man participants should agree to use and utilize an adequate method of contraception throughout treatment and for at least 2 months after study is stopped.
• Subjects volunteered to join the study, signed informed consent, good compliance, with follow-up.

You may not qualify if:

• Patients with active bleeding within 2 months of primary and/or metastatic lesions;
• Patients with previous arterial/venous thrombosis events within 6 months, such as cerebrovascular accidents (including temporary ischemic attack), deep venous thrombosis or pulmonary embolism;
• Patients who are receiving thrombolytic or anticoagulant therapies such as warfarin, heparin, or their analogists; allowed to take low-dose heparin (6000 to 12,000 U/d for adults) or low-dose aspirin (≤100 mg/d) for prophylactic purposes with an INR≤1.5×ULN;
• Gastrointestinal diseases with a bleeding tendency (such as active gastrointestinal ulcer) or be likely to cause gastrointestinal bleeding, perforation, or obstruction, or patients with fistula;
• Have undergone major surgery (craniotomy, thoracotomy or open surgery) within 4 weeks prior to the first dose study;
• HER2-positive gastric adenocarcinoma;
• A history of immunodeficiency, including a positive HIV test or other acquired, congenital immunodeficiency disease, or a history of organ transplantation;
• A variety of factors affecting oral medications (such as inability to swallow, chronic diarrhea, and intestinal obstruction);
• Symptomatic central nervous system metastasis and/or cancerous meningitis are known to exist;
• Patients with any severe and / or uncontrolled disease, including: Patients with hypertension that cannot be well controlled by single antihypertensive therapy (SBP ≥150 mmHg, Diastolic BP ≥100mmHg); Or taking two or more antihypertensive drugs to control blood pressure; Acute myocardial infarction, malignant arrhythmias (including QT interval \> 450ms in men and \> 470ms in women) and ≥2 grade congestive heart failure (NYHA grade); Active or uncontrolled severe infection (NCI-CTC AE grade ≥2 infection); Liver diseases such as cirrhosis, decompensated liver disease, active hepatitis, or chronic hepatitis (HBV-DNA \> 1000 IU/mL) require antiviral therapy; Diabetic patients with poor blood glucose control (fasting blood glucose (FBG) \> 10 mmol/L); Routine urine indicated urine protein ≥ ++, and confirmed 24-hour urine protein quantitative \> 1.0 g;
• Clinically significant ascites, including any ascites that can be found on a physical examination, ascites that has been treated or currently in need of treatment, and only those with a small amount of ascites but no symptoms can be selected;
• A moderate amount of fluid in both sides of the chest, or a large amount of fluid in one side of the chest, or has caused respiratory dysfunction Patient to be drained;
• Uncontrolled metabolic disorders or other non-malignant organs or secondary reactions to systemic diseases or cancers that may lead to higher medical risk and/or uncertainty in survival evaluation;
• Known to have active tuberculosis;
• Suffering from interstitial lung disease requiring steroid therapy;

Sponsors & Collaborators

• Ruijin Hospital: lead
• Chia Tai Tianqing Pharmaceutical Group Co., Ltd.: collaborator

Study Sites (7)

Jiangsu Cancer Hospital

Nanjing, Jiangsu, China

NOT YET RECRUITING

Jiangsu Province Hospital

Nanjing, Jiangsu, China

NOT YET RECRUITING

Affiliated Hospital of Jiannan University

Wuxi, Jiangsu, China

NOT YET RECRUITING

Wuxi Branch of Rujin Hospital

Wuxi, Jiangsu, China

RECRUITING

Jiading Cental Hospital Shanghai University of Medicine & Health Sciences

Shanghai, China

RECRUITING

Ruijin Hospital

Shanghai, China

RECRUITING

Tongji Hospital of Tongji University

Shanghai, China

NOT YET RECRUITING

Related Publications (2)

• Wu JW, Zhou CF, Han ZX, Zhang H, Yan J, Chen J, Wang CB, Qin ZQ, Mao Y, Tang XY, Zhu LJ, Wei XW, Cui DH, Yang XL, Shi M, Zhao LQ, Jiang JL, Zhu WY, Wang HM, Wang C, Zhu LJ, Zhang J. Anlotinib plus chemotherapy as a first-line treatment for gastrointestinal cancer patients with unresectable liver metastases: a multicohort, multicenter, exploratory trial. Signal Transduct Target Ther. 2024 Dec 9;9(1):344. doi: 10.1038/s41392-024-02051-4.

  PMID: 39648217 DERIVED

• Li H, Feng H, Zhang T, Wu J, Shen X, Xu S, Xu L, Wang S, Zhang Y, Jia W, Ji X, Cheng X, Zhao R. CircHAS2 activates CCNE2 to promote cell proliferation and sensitizes the response of colorectal cancer to anlotinib. Mol Cancer. 2024 Mar 21;23(1):59. doi: 10.1186/s12943-024-01971-7.

  PMID: 38515149 DERIVED

MeSH Terms

Conditions

Digestive System Neoplasms

Interventions

anlotinib; Oxaliplatin; Capecitabine; Cisplatin; Paclitaxel; Docetaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Central Study Contacts

Jun Zhang, Ph. D

CONTACT

+86-21-64370045; junzhang10977@sjtu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 21, 2022
• First Posted: March 2, 2022
• Study Start: December 1, 2021
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2024
• Last Updated: November 28, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (7)