A Study of AL2846 Capsule Combined With Standard Chemotherapy Regimen in Subjects With Advanced Colorectal Cancer

Study Overview
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Brief Summary
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This is a study to explore the safety, tolerance and efficacy of AL2846 capsules combined with mFOLFOLX6 or FOLFIRI standard chemotherapy regimen in subjects with advanced metastatic colorectal cancer.

Official Title
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A Phase Ib Study to Evaluate the Efficacy and Safety of AL2846 Capsule Combined With Chemotherapy (mFOLFOX6 or FOLFIRI)Versus Placebo Combined With Chemotherapy in Subjects With Advanced Colorectal Cancer

Conditions
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Advanced Colorectal Cancer

Intervention / Treatment
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* Drug: AL2846
* Drug: Calcium folate
* Drug: 5-FU
* Drug: Oxaliplatin
* Drug: Irinotecan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: -1. Histologically confirmed advanced metastatic colorectal cancer. 2. Has received only first-line standard chemotherapy regimen for metastatic disease, and which was failed. 3. At least one measurable lesion. 4. Has received systemic chemotherapy, palliative radiotherapy or other anti-tumor therapy before first dose at least 4 weeks. 5.18 and 75 years old; Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1; Life expectancy ≥ 3 months. 6. Adequate laboratory indicators. 7. No pregnant or breastfeeding women, and a negative pregnancy test. 8. Understood and signed an informed consent form. Exclusion Criteria: 1. Diagnosed and/or treated additional malignancy within 5 years with the exception of basal cell carcinoma of the skin and carcinoma in situ of the cervix. 2. Has received radiotherapy, chemotherapy and surgery before and less than 4 weeks from the first administration and less than 5 half-lives of oral targeted drugs after the completion of treatment. 3. Has multiple factors that affect oral medications. 4. Has gastroduodenal ulcer, ulcerative colitis, intestinal obstruction and other gastrointestinal diseases or other conditions judged by the investigator that may cause gastrointestinal bleeding or perforation. 5. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage. 6. Has arterial or deep vein thrombosis events in 6 months. 7. Hypersensitivity to AL2846 or its excipient. 8. Imaging (CT or MRI) shows that tumor invades large blood vessels or the boundary with blood vessels is unclear. 9. Has symptomatic brain metastases, spinal cord compression, and cancerous meningitis within 8 weeks,or brain or pia mater disease confirmed by CT or MRI examination before the first dose. 10.Has adverse events caused by previous therapy that did not recover to ≤ grade 1, with the exception of alopecia or ≥ grade 2 neurotoxicity caused by Oxaliplatin. 11. Subjects plan to receive FOLFIRI chemotherapy regimen with uridine diphosphate glucuronyltransferase homozygous variant or double hybrid variant. 12. Has drug abuse history that unable to abstain from or mental disorders. 13. Has any serious and/or uncontrolled disease. 14. Has received allogeneic organ transplants, hematopoietic stem cell transplants or bone marrow transplants. 15. Has participated in other clinical trials within 4 weeks before the first dose. 16. According to the investigators' judgment.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AL2846 + mFOLFOX6<br>AL2846 capsule administered orally,once daily in 28-day cycle; oxaliplatin 85mg/ ㎡ administered intravenously (IV) on day 1, day 15 in 28-day cycle；calcium folate 400mg/ ㎡ IV on day 1, day 15 in 28-day cycle；5-fu 2800mg/ ㎡ IV on day 1, 2, 15, 16 in 28-day cycle. | Drug: AL2846<br>* AL2846 is a multi-target receptor tyrosine kinase inhibitor, which has obvious selectivity for c-met.<br>Drug: Calcium folate<br>* Calcium folate 400mg/ ㎡ IV on day 1,15 in 28-day cycle<br>Drug: 5-FU<br>* 5-FU 2800mg/ ㎡ IV on day 1, 2, 15, 16 days in 28-day cycle.<br>Drug: Oxaliplatin<br>* Oxaliplatin 85mg/ ㎡ administered intravenously (IV) on day 1, day 15 in 28-day cycle.<br>|
| Experimental: AL2846 + FOLFIRI<br>AL2846 capsule administered orally,once daily in 28-day cycle; irinotecan 180mg/㎡ administered intravenously (IV) on day 1,15 in 28-day cycle; calcium folate 400mg/ ㎡ IV on day 1,15 in 28-day cycle; 5-fu 2800mg/ ㎡ IV on day 1, 2, 15, 16 days in 28-day cycle. | Drug: AL2846<br>* AL2846 is a multi-target receptor tyrosine kinase inhibitor, which has obvious selectivity for c-met.<br>Drug: Calcium folate<br>* Calcium folate 400mg/ ㎡ IV on day 1,15 in 28-day cycle<br>Drug: 5-FU<br>* 5-FU 2800mg/ ㎡ IV on day 1, 2, 15, 16 days in 28-day cycle.<br>Drug: Irinotecan<br>* Irinotecan 180mg/㎡ administered intravenously (IV) on day 1,15 in 28-day cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | PFS defined as the time from the first dose until the first documented progressive disease (PD) or death from any cause, based on investigator. | up to 12 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) | Percentage of participants achieving complete response (CR) and partial response (PR). | up to 12 month | 
| Disease control rate（DCR） | Percentage of participants achieving complete response (CR) and partial response (PR) and stable disease (SD). | up to 12 month | 
| Duration of response (DOR) | The time when the participants first achieved complete or partial remission to disease progression. | up to 12 month |