Anlotinib Combined With mXELIRI as Second-line Treatment of Advanced Colorectal Cancer

NCT05035914 | Unknown Phase 1

• 1 other identifier: Guangzhouucm
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 1

Brief Summary

1. 1.Determine the maximum tolerable dose (MTD) and / or phase II recommended dose (RP2D) of the allotinib combined mXELIRI protocol.
2. 2.To evaluate the safety and tolerance of the combination of anlotinib and mXELIRI in the second-line treatment of patients with advanced colorectal cancer

Conditions

Advanced Colorectal Cancer

Keywords

advanced colorectal cancer

Outcome Measures

Primary Outcomes (3)

• Maximum tolerated dose (MTD)

  The main side effects of drugs are the main reasons for limiting the increase of the dose of chemotherapy drugs, which are dose limiting toxicity of chemotherapy drugs

  Through study completion, up to 24 months

• Phase II clinical recommended dose (RP2D)

  When the minimum number of patients is included in the dose increasing phase, the recommended dose of phase 2 can be determined accurately and quickly

  each 42 days up to intolerance the toxicity or PD

• Objective response rate

  Objective response rate is defined as the percentage of subjects with evidence of a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1.prior to progression or any further therapy.

  Through study completion, up to 24 months

Secondary Outcomes (5)

• Progression free survival

  From date of enrollment until the date of first documented progression, assessed up to 24 months

• Overall survival

  From date of enrollment until death, assessed up to 24 months

• Disease control rate

  Through study completion, up to 24 months

• Duration of remission

  Through study completion, up to 24 months

• Score of quality of Life

  From date of enrollment until death, assessed up to 24 months

Study Arms (1)

Experimental: anlotinib+mXELIRI

EXPERIMENTAL

Dose-escalation phase: A: anlotinib 8 mg, po, qd, d1-14; iritecan 180-200mg/m2, iv, d1;capecitabine 800mg/m2, po, bid, d1-14; every 3 weeks as a cycle; B: anlotinib 10 mg, po, qd, d1-14; iritecan 180-200mg/m2, iv, d1;capecitabine 800mg/m2, po, bid, d1-14; every 3 weeks as a cycle; C: anlotinib 12 mg, po, qd, d1-14; iritecan 180-200mg/m2, iv, d1;capecitabine 800mg/m2, po, bid, d1-14; every 3 weeks as a cycle; Dose-expansion phase: anlotinib RP2D, po, qd, d1-14; iritecan 180-200mg/m2, iv, d1;capecitabine 800mg/m2, po, bid, d1-14; every 3 weeks as a cycle;

Drug: Anlotinib Hydrochloride

Interventions

Anlotinib Hydrochloride DRUG

Anlotinib Hydrochloride is a capsule in the form of 8 mg ,10 mg and 12 mg, orally, once daily, 2 weeks on/1 week off.

Experimental: anlotinib+mXELIRI

Eligibility Criteria

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

You may qualify if:

• ECOG performance status (PS) 0-1
• The expected survival time is not less than 12 weeks
• Patients with stage IV colorectal cancer confirmed by pathology or imaging have measurable lesions (according to RECIST 1.1, the long diameter of tumor lesions on CT scan is greater than or equal to 10 mm, the short diameter of lymph node lesions on CT scan is greater than or equal to 15 mm, and the measurable lesions have not received radiotherapy, freezing and other local treatment);
• First line patients with advanced or intolerant colorectal cancer treated with bevacizumab combined with oxaliplatin (FOLFOX or capeox, etc.);
• The function of main organs was normal (in accordance with the chemotherapy standard);
• Women of childbearing age must have taken reliable contraceptive measures or conducted pregnancy test (serum or urine) within 7 days before enrollment, and the result is negative, and they are willing to use appropriate contraceptive methods during the test period and 8 weeks after the last administration of the test drug. For men, it is necessary to agree to use appropriate contraceptive methods or surgical sterilization during the trial period and 8 weeks after the last administration of the trial drug;
• The subjects volunteered to join the study and signed informed consent, with good compliance and follow-up.

You may not qualify if:

• The histological type was mucinous adenocarcinoma or ovarian implant metastasis;
• First line patients with irinotecan treatment;
• Patients who had been treated with anlotinib hydrochloride capsules in the past;
• Symptomatic brain metastases (patients with stable symptoms and completed treatment 21 days before enrollment can be enrolled, but no cerebral hemorrhage symptoms should be confirmed by brain MRI, CT or venography evaluation);
• Patients with hypertension who could not be well controlled by single antihypertensive drug treatment (systolic blood pressure ≥ 150 mmHg, diastolic blood pressure ≥ 100 mmHg); Or use two or more antihypertensive drugs to control blood pressure
• The patient also had more than 1 degree of adverse reactions (except hair loss, neurotoxicity more than 2 degrees) which could not be alleviated due to previous treatment;
• They have the following cardiovascular diseases: myocardial ischemia or myocardial infarction above grade II, poorly controlled arrhythmias (including QTc interval ≥ 450 ms for male and ≥ 470 MS for female); According to NYHA criteria, grade Ⅲ - Ⅳ cardiac insufficiency, or left ventricular ejection fraction (LVEF) \< 50% by echocardiography;
• Abnormal coagulation function (INR \> 1.5 or PT \> ULN + 4 seconds or APTT \> 1.5 ULN), bleeding tendency or receiving thrombolysis or anticoagulation therapy;
• There were significant clinical bleeding symptoms or clear bleeding tendency in the first 3 months, such as gastrointestinal bleeding, hemorrhagic hemorrhoids, hemorrhagic gastric ulcer, baseline fecal occult blood + + or above, or vasculitis;
• Arteriovenous thrombotic events occurred in the first 12 months, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep venous thrombosis and pulmonary embolism;
• Known hereditary or acquired bleeding and thrombotic tendency (such as hemophilia, coagulation dysfunction, thrombocytopenia, hypersplenism, etc.);
• Wound or fracture that has not been cured for a long time (pathological fracture caused by tumor is not included);
• Patients in the study group had undergone major surgery or severe traumatic injury, fracture or ulcer within 4 weeks;
• There are obvious factors affecting oral drug absorption, such as inability to swallow, chronic diarrhea and intestinal obstruction;
• Abdominal fistula, gastrointestinal perforation or abdominal abscess occurred within 6 months before admission;

Sponsors & Collaborators

• Guangzhou University of Traditional Chinese Medicine: lead
• Guangdong Provincial Hospital of Traditional Chinese Medicine: collaborator

Study Sites (1)

Guangdong Provincial Hospital of Chinese Medicine

Guangzhou, Guangdong, 510120, China

RECRUITING

Study Officials

• Haibo Zhang, Professor

  Guangdong Provincial Hospital of Traditional Chinese Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Haibo Zhang, Professor

CONTACT

86 20 81887233; doctorllr@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2021
• First Posted: September 5, 2021
• Study Start: July 9, 2021
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2024
• Last Updated: September 5, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)