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

NCT04080843 | Completed Phase 2

• 1 other identifier: ALTER-C-002
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

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

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Objective response rate(ORR)

  using RECIST version 1.1

  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 Outcomes (4)

• Progression-free survival (PFS)

  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

• Disease control rate (DCR)

  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

• Duration of Response (DoR)

  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

• Safety: NCI CTC AE Version 4.0.3

  from day 1 of first dosing to 30 days after permanent discontinuation of Anlotinib

Study Arms (1)

Group A

EXPERIMENTAL

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.

Drug: Anlotinib Hydrochloride; Drug: Capecitabine; Drug: Oxaliplatin

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.

Group A

Capecitabine DRUG

Capecitabine is a capsule in the form of 500 mg, orally, 850 mg/m2, twice daily, 2 weeks on/1 week off.

Group A

Oxaliplatin DRUG

Oxaliplatin 130 mg/m2,D1

Group A

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Zhejiang University: lead
• Chia Tai Tianqing Pharmaceutical Group Co., Ltd.: collaborator

Study Sites (2)

The Second Affiliated Hospital of Zhejiang University

Hangzhou, Zhejiang, 310000, China

Location

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China

Location

Related Publications (1)

• 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.

  PMID: 35513832 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Interventions

Capecitabine; Oxaliplatin

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Organic Chemicals

Study Design

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

Study Record Dates

• First Submitted: September 3, 2019
• First Posted: September 6, 2019
• Study Start: November 15, 2019
• Primary Completion: June 1, 2022
• Study Completion: July 1, 2022
• Last Updated: July 13, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)