Anlotinib Plus Chemotherapy as First-line Therapy for Gastrointestinal Tumor Patients With Unresectable Liver Metastasis: A Multi-cohort, Multi-center Clinical Trial (ALTER-G-001)

Ruijin Hospital7 sites in 1 country116 target enrollmentDecember 1, 2021

InterventionsAnlotinib + Oxaliplatin + Capecitabine Anlotinib + Cisplatin + Paclitaxel/ Docetaxel Anlotinib + Standard first-line chemotherapy

DrugsAnlotinib + Oxaliplatin + Capecitabine Anlotinib + Cisplatin + Paclitaxel/ Docetaxel Anlotinib + Standard first-line chemotherapy

Overview

Phase: Phase 2
Intervention: Anlotinib + Oxaliplatin + Capecitabine
Conditions: Gastrointestinal Tumors
Sponsor: Ruijin Hospital
Enrollment: 116
Locations: 7
Primary Endpoint: Objective response rate (ORR)
Status: Recruiting
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

December 1, 2021

End Date

December 1, 2024

Last Updated

2 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Ruijin Hospital

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•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.

Exclusion Criteria

•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;

Arms & Interventions

Experimental: Experimental group 1

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

Intervention: Anlotinib + Oxaliplatin + Capecitabine

Experimental: Experimental group 2

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

Intervention: Anlotinib + Cisplatin + Paclitaxel/ Docetaxel

Experimental: Experimental group 3

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

Intervention: Anlotinib + Standard first-line chemotherapy

Outcomes

Primary Outcomes

Objective response rate (ORR)

Time Frame: up to 24 months

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.

Secondary Outcomes

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)
Radical Resection Rate of Liver Metastases(Up to 6 cycles)