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

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

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.

Study Overview

• Status: Unknown
• Conditions: Advanced Colorectal Cancer
• Intervention / Treatment: Drug: AL2846; Drug: Calcium folate; Drug: 5-FU; Drug: Oxaliplatin; Drug: Irinotecan

• Study Type: Interventional
• Enrollment (Anticipated): 56
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Liaoning
    • Shengyang, Liaoning, China, 110011
      • Recruiting
      • The First Hospital of China Medical University
      • Contact: Yunpeng Liu, Doctor; Email: cmu_trial@163.com
      • Sub-Investigator: Yunpeng Liu, Doctor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2020
• Primary Completion (Anticipated): December 31, 2020
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: April 6, 2020
• First Submitted That Met QC Criteria: April 6, 2020
• First Posted (Actual): April 8, 2020

Study Record Updates

• Last Update Posted (Actual): July 21, 2020
• Last Update Submitted That Met QC Criteria: July 20, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Calcium-Regulating Hormones and Agents; Topoisomerase I Inhibitors; Oxaliplatin; Irinotecan; Calcium
• Other Study ID Numbers: AL2846-I-0004

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No