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Anlotinib Hydrochloride Capsules Combined With CAPEOX in RAS and BRAF Wild-type mCRC Patients (ALTER-C-002)

Primary Purpose

Colorectal Cancer, RAS and BRAF Wild-type, Colorectal Neoplasms

Status
Completed
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Anlotinib Hydrochloride
Capecitabine
Oxaliplatin
Sponsored by
Zhejiang University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Cancer

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • At least one measurable lesion (the length of spiral CT scan (> 10mm) meets the requirements of RESCIST 1.1) is found in patients with HCC confirmed by histopathology or cytology or who meet the clinical diagnostic criteria.
  • ≥ 18 and ≤ 75 years of age
  • ECOG performance status of 0-1
  • No prior treatment for advanced disease (adjuvant therapy allowed)
  • Life expectancy of at least 3 months
  • The main organs are functioning normally.
  • Neutrophils count =/> 1.5 x 109/L, platelets count =/> 100 x 109/L, HGB =/> 90 g/L
  • total bilirubin =/< 1.5 x UNL • SGOT and SGPT =/< 2.5 x UNL (=/< 5 x UNL in patients with liver metastases)
  • Creatinine =/< 1.5 x UNL
  • Patients who are molecularly diagnosed as having RAS and BRAF wild-type mCRC are Histologically/cytologically confirmed as advanced, colorectal cancer.
  • Subjects volunteered to join the study, signed informed consent, good compliance, with follow-up.

Exclusion Criteria:

  • Pregnant or lactating women.
  • Active or untreated CNS metastases as determined by CT or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments.
  • Patients with hypertension who could not be well controlled by antihypertensive drugs (systolic blood pressure > 150 mmHg, diastolic blood pressure > 100 mmHg), patients with myocardial infarction, arrhythmias with poor control (including QTC interval > 450 ms) and cardiac insufficiency of grade II according to NYHA standard.
  • with bleeding tendency or undergoing thrombolysis or anticoagulation therapy.
  • serious uncontrolled intercurrence infection.
  • Proteinuria ≥ 2+ (1.0g/24hr).
  • Have evidence or a history of bleeding tendency within two months of the enrollment, regardless of seriousness.
  • Within 6 months before the first treatment occurs artery/venous thromboembolic events, such as cerebral vascular accident (including transient ischemic attack) etc.
  • Have a history of mental illness or psychotropic drug abuse.
  • Patients with a history of immunodeficiency(or autoimmue disease), or other acquired congenital immunodeficiency diseases, or a history of organ transplantation and hematopoietic stem cell transplantation.
  • Patients who are allergic to components of Capecitabine preparations, Oxaliplatin injection and anlotinib preparations.
  • According to the researchers' judgment, there are serious concomitant diseases that endanger patient safety or prevent patients from completing the study.
  • Patients who have received prior systemic chemotherapy, targeted therapy, immunity therapy or any medication within 30 days.

Sites / Locations

  • The Second Affiliated Hospital of Zhejiang University
  • Zhejiang Cancer Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Group A

Arm Description

Patients in the study group will receive the following treatment: 21 days as a treatment cycle, Anlotinib 12 mg/day, Orally(D1-D14); Capecitabine 850 mg/m2,Orally(D1-D14), Bid; Oxaliplatin 130 mg/m2, iv(D1). If anlotinib is not tolerated(except Hand-foot skin reaction), the dose can be reduced to 10mg or 8mg ,until un-tolerable toxicity again. After 6 cycles of combined therapy, patients will receive capecitabine and anlotinib as maintenance therapy until tumor progression.

Outcomes

Primary Outcome Measures

Objective response rate(ORR)
using RECIST version 1.1

Secondary Outcome Measures

Progression-free survival (PFS)
using RECIST version 1.1
Disease control rate (DCR)
using RECIST version 1.1
Duration of Response (DoR)
using RECIST version 1.1
Safety: NCI CTC AE Version 4.0.3
Safety will be evaluated by incidence, severity and outcomes of adverse events (AEs) and categorized by severity in accordance with the NCI CTC AE Version 4.0.3

Full Information

First Posted
September 3, 2019
Last Updated
July 12, 2022
Sponsor
Zhejiang University
Collaborators
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT04080843
Brief Title
Anlotinib Hydrochloride Capsules Combined With CAPEOX in RAS and BRAF Wild-type mCRC Patients
Acronym
ALTER-C-002
Official Title
An Open, Single Arm, Multicenter, Exploratory Phase II Clinical Trial of Anlotinib Hydrochloride Capsules Combined With CAPEOX in RAS and BRAF Wild-type Patients With Metastatic Colorectal Carcinoma as 1st Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Completed
Study Start Date
November 15, 2019 (Actual)
Primary Completion Date
June 1, 2022 (Actual)
Study Completion Date
July 1, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Zhejiang University
Collaborators
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
This is an Open, Single Arm, Exploratory and Phase II Clinical Trial of Anlotinib Hydrochloride Capsules Combined With CAPEOX in RAS and BRAF wild-type patients with Metastatic Colorectal Carcinoma(CRC) as 1st Therapy. After 6 cycles of combined therapy, patients will receive capecitabine and anlotinib as maintenance therapy until tumor progression.In order to observe and evaluate the efficacy and safety of Anlotinib Hydrochloride Capsules combined with CAPEOX in treatment of patients with mCRC. The patients who are pathologically confirmed as RAS and BRAF wild-type mCRC will be enrolled. Condition or disease Invention/treatment Phase Colorectal Cancer Drug: Anlotinib Hydrochloride Drug: Capecitabine Drug: Oxaliplatin Phase 2
Detailed Description
This is an Open, Single Arm, Exploratory and Phase II Clinical Trial of Anlotinib Hydrochloride Capsules Combined With CAPEOX in RAS and BRAF wild-type patients with Metastatic Colorectal Carcinoma(CRC) as 1st Therapy. After 6 cycles of combined therapy, patients will receive capecitabine and anlotinib as maintenance therapy until tumor progression.In order to observe and evaluate the efficacy and safety of Anlotinib Hydrochloride Capsules combined with CAPEOX in treatment of patients with Metastatic Colorectal Carcinoma(mCRC).Primary Efficacy Endpoint: Objective Response Rate (ORR), Secondary Efficacy Endpoints: Progression free survival (PFS) (According to RECIST Version 1.1), Disease Control Rate (DCR) and duration of response(DoR). Safety and tolerance will be evaluated by incidence, severity and outcomes of AEs and categorized by severity in accordance with the NCI CTC AE Version 4.0.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer, RAS and BRAF Wild-type, Colorectal Neoplasms, Intestinal Neoplasms, Gastrointestinal Neoplasms, Digestive System Neoplasms, Neoplasms by Site, Neoplasms, Digestive System Diseases, Gastrointestinal Diseases, Colonic Diseases, Intestinal Diseases, Rectal Diseases

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group A
Arm Type
Experimental
Arm Description
Patients in the study group will receive the following treatment: 21 days as a treatment cycle, Anlotinib 12 mg/day, Orally(D1-D14); Capecitabine 850 mg/m2,Orally(D1-D14), Bid; Oxaliplatin 130 mg/m2, iv(D1). If anlotinib is not tolerated(except Hand-foot skin reaction), the dose can be reduced to 10mg or 8mg ,until un-tolerable toxicity again. After 6 cycles of combined therapy, patients will receive capecitabine and anlotinib as maintenance therapy until tumor progression.
Intervention Type
Drug
Intervention Name(s)
Anlotinib Hydrochloride
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Intervention Description
Capecitabine is a capsule in the form of 500 mg, orally, 850 mg/m2, twice daily, 2 weeks on/1 week off.
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Intervention Description
Oxaliplatin 130 mg/m2,D1
Primary Outcome Measure Information:
Title
Objective response rate(ORR)
Description
using RECIST version 1.1
Time Frame
Every 2 weeks until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months
Secondary Outcome Measure Information:
Title
Progression-free survival (PFS)
Description
using RECIST version 1.1
Time Frame
every 2 weeks until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months
Title
Disease control rate (DCR)
Description
using RECIST version 1.1
Time Frame
every 2 weeks until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months
Title
Duration of Response (DoR)
Description
using RECIST version 1.1
Time Frame
every 2 weeks until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months
Title
Safety: NCI CTC AE Version 4.0.3
Description
Safety will be evaluated by incidence, severity and outcomes of adverse events (AEs) and categorized by severity in accordance with the NCI CTC AE Version 4.0.3
Time Frame
from day 1 of first dosing to 30 days after permanent discontinuation of Anlotinib

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: At least one measurable lesion (the length of spiral CT scan (> 10mm) meets the requirements of RESCIST 1.1) is found in patients with HCC confirmed by histopathology or cytology or who meet the clinical diagnostic criteria. ≥ 18 and ≤ 75 years of age ECOG performance status of 0-1 No prior treatment for advanced disease (adjuvant therapy allowed) Life expectancy of at least 3 months The main organs are functioning normally. Neutrophils count =/> 1.5 x 109/L, platelets count =/> 100 x 109/L, HGB =/> 90 g/L total bilirubin =/< 1.5 x UNL • SGOT and SGPT =/< 2.5 x UNL (=/< 5 x UNL in patients with liver metastases) Creatinine =/< 1.5 x UNL Patients who are molecularly diagnosed as having RAS and BRAF wild-type mCRC are Histologically/cytologically confirmed as advanced, colorectal cancer. Subjects volunteered to join the study, signed informed consent, good compliance, with follow-up. Exclusion Criteria: Pregnant or lactating women. Active or untreated CNS metastases as determined by CT or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments. Patients with hypertension who could not be well controlled by antihypertensive drugs (systolic blood pressure > 150 mmHg, diastolic blood pressure > 100 mmHg), patients with myocardial infarction, arrhythmias with poor control (including QTC interval > 450 ms) and cardiac insufficiency of grade II according to NYHA standard. with bleeding tendency or undergoing thrombolysis or anticoagulation therapy. serious uncontrolled intercurrence infection. Proteinuria ≥ 2+ (1.0g/24hr). Have evidence or a history of bleeding tendency within two months of the enrollment, regardless of seriousness. Within 6 months before the first treatment occurs artery/venous thromboembolic events, such as cerebral vascular accident (including transient ischemic attack) etc. Have a history of mental illness or psychotropic drug abuse. Patients with a history of immunodeficiency(or autoimmue disease), or other acquired congenital immunodeficiency diseases, or a history of organ transplantation and hematopoietic stem cell transplantation. Patients who are allergic to components of Capecitabine preparations, Oxaliplatin injection and anlotinib preparations. According to the researchers' judgment, there are serious concomitant diseases that endanger patient safety or prevent patients from completing the study. Patients who have received prior systemic chemotherapy, targeted therapy, immunity therapy or any medication within 30 days.
Facility Information:
Facility Name
The Second Affiliated Hospital of Zhejiang University
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310000
Country
China
Facility Name
Zhejiang Cancer Hospital
City
Hangzhou
State/Province
Zhejiang
Country
China

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35513832
Citation
Liu Y, Xiao Q, He J, Hu H, Du J, Zhu Y, Chen J, Liu Z, Wang J, Sun L, Xu D, Li J, Liao X, Wang J, Cai Y, Cai C, Jin Z, Wang L, Yuan Y, Ding K. Phase II study of anlotinib in combination with oxaliplatin and capecitabine for patients with RAS/BRAF wild-type metastatic colorectal adenocarcinoma as the first-line therapy. BMC Med. 2022 May 6;20(1):155. doi: 10.1186/s12916-022-02357-6.
Results Reference
derived

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Anlotinib Hydrochloride Capsules Combined With CAPEOX in RAS and BRAF Wild-type mCRC Patients

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