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

NCT ID: NCT04080843

Last Updated: 2022-07-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-11-15
• Study Completion Date: 2022-07-01

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.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group A

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.

Group Type: EXPERIMENTAL

Anlotinib Hydrochloride

Intervention Type: 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.

Capecitabine

Intervention Type: DRUG

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

Oxaliplatin

Intervention Type: DRUG

Oxaliplatin 130 mg/m2,D1

Interventions

Anlotinib Hydrochloride

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

Capecitabine

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

Oxaliplatin

Oxaliplatin 130 mg/m2,D1

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Zhejiang University

OTHER

Sponsor Role: lead

Responsible Party

Ding Ke-Feng

Clinical professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

The Second Affiliated Hospital of Zhejiang University

Hangzhou, Zhejiang, China

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China

Countries

China

References

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.

Reference Type: DERIVED

PMID: 35513832 (View on PubMed)

Other Identifiers

ALTER-C-002

Identifier Type: -

Identifier Source: org_study_id