## Protocol Section
### Identification Module
**NCT ID:** NCT04337879

**Brief Title:** A Study of AL2846 Capsule Combined With Standard Chemotherapy Regimen in Subjects With Advanced Colorectal Cancer

**Official Title:** 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

#### Organization Study ID Info
**ID:** AL2846-I-0004
#### Organization
**Class:** INDUSTRY
**Full Name:** Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
### Status Module
#### Completion Date
**Date:** 2020-12-31

**Type:** ESTIMATED

#### Expanded Access Info
**Last Known Status:** RECRUITING
#### Last Update Post Date
**Date:** 2020-07-21

**Type:** ACTUAL

**Last Update Submit Date:** 2020-07-20

**Overall Status:** UNKNOWN

#### Primary Completion Date
**Date:** 2020-12-31

**Type:** ESTIMATED

#### Start Date
**Date:** 2020-07-20

**Type:** ACTUAL

**Status Verified Date:** 2020-01

#### Study First Post Date
**Date:** 2020-04-08
**Type:** ACTUAL
**Study First Submit Date:** 2020-04-06
**Study First Submit QC Date:** 2020-04-06
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

### Description Module

**Brief Summary:** 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.

### Conditions Module

**Conditions:**

- Advanced Colorectal Cancer

### Design Module

#### Design Info

**Allocation:** NON_RANDOMIZED

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 56

**Type:** ESTIMATED

**Phases:**

- PHASE1

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** 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.

**Intervention Names:**

- Drug: AL2846

- Drug: Calcium folate

- Drug: 5-FU

- Drug: Oxaliplatin

**Label:** AL2846 + mFOLFOX6

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** 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.

**Intervention Names:**

- Drug: AL2846

- Drug: Calcium folate

- Drug: 5-FU

- Drug: Irinotecan

**Label:** AL2846 + FOLFIRI

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- AL2846 + FOLFIRI

- AL2846 + mFOLFOX6

**Description:** AL2846 is a multi-target receptor tyrosine kinase inhibitor, which has obvious selectivity for c-met.

**Name:** AL2846

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- AL2846 + FOLFIRI

- AL2846 + mFOLFOX6

**Description:** Calcium folate 400mg/ ㎡ IV on day 1,15 in 28-day cycle

**Name:** Calcium folate

**Type:** DRUG

#### Intervention 3

**Arm Group Labels:**

- AL2846 + FOLFIRI

- AL2846 + mFOLFOX6

**Description:** 5-FU 2800mg/ ㎡ IV on day 1, 2, 15, 16 days in 28-day cycle.

**Name:** 5-FU

**Type:** DRUG

#### Intervention 4

**Arm Group Labels:**

- AL2846 + mFOLFOX6

**Description:** Oxaliplatin 85mg/ ㎡ administered intravenously (IV) on day 1, day 15 in 28-day cycle.

**Name:** Oxaliplatin

**Type:** DRUG

#### Intervention 5

**Arm Group Labels:**

- AL2846 + FOLFIRI

**Description:** Irinotecan 180mg/㎡ administered intravenously (IV) on day 1,15 in 28-day cycle.

**Name:** Irinotecan

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** PFS defined as the time from the first dose until the first documented progressive disease (PD) or death from any cause, based on investigator.

**Measure:** Progression-free survival (PFS)

**Time Frame:** up to 12 month

#### Secondary Outcomes

**Description:** Percentage of participants achieving complete response (CR) and partial response (PR).

**Measure:** Overall response rate (ORR)

**Time Frame:** up to 12 month

**Description:** Percentage of participants achieving complete response (CR) and partial response (PR) and stable disease (SD).

**Measure:** Disease control rate（DCR）

**Time Frame:** up to 12 month

**Description:** The time when the participants first achieved complete or partial remission to disease progression.

**Measure:** Duration of response (DOR)

**Time Frame:** up to 12 month

### Eligibility Module

**Eligibility Criteria:** 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.

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** cmu_trial@163.com

**Name:** Yunpeng Liu, Doctor

**Phone:** 024-83282256

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Shengyang

**Contacts:**

***Contact 1:***

- **Email:** cmu_trial@163.com

- **Name:** Yunpeng Liu, Doctor

- **Role:** CONTACT

***Contact 2:***

- **Name:** Yunpeng Liu, Doctor

- **Role:** SUB_INVESTIGATOR

**Country:** China

**Facility:** The First Hospital of China Medical University

**State:** Liaoning

**Status:** RECRUITING

**Zip:** 110011

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000007414

- Term: Intestinal Neoplasms

- ID: D000005770

- Term: Gastrointestinal Neoplasms

- ID: D000004067

- Term: Digestive System Neoplasms

- ID: D000009371

- Term: Neoplasms by Site

- ID: D000009369

- Term: Neoplasms

- ID: D000004066

- Term: Digestive System Diseases

- ID: D000005767

- Term: Gastrointestinal Diseases

- ID: D000003108

- Term: Colonic Diseases

- ID: D000007410

- Term: Intestinal Diseases

- ID: D000012002

- Term: Rectal Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC06

- Name: Digestive System Diseases

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M17890

- Name: Colorectal Neoplasms

- Relevance: HIGH

- As Found: Colorectal Cancer

- ID: M10448

- Name: Intestinal Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M8886

- Name: Gastrointestinal Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M7256

- Name: Digestive System Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M7255

- Name: Digestive System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M8883

- Name: Gastrointestinal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M6336

- Name: Colonic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M10444

- Name: Intestinal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14844

- Name: Rectal Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000015179

- Term: Colorectal Neoplasms

### Intervention Browse Module - Ancestors

- ID: D000077264

- Term: Calcium-Regulating Hormones and Agents

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000000970

- Term: Antineoplastic Agents

- ID: D000059004

- Term: Topoisomerase I Inhibitors

- ID: D000059003

- Term: Topoisomerase Inhibitors

- ID: D000004791

- Term: Enzyme Inhibitors

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Micro

- Name: Micronutrients

- Abbrev: Hemat

- Name: Hematinics

- Abbrev: BDCA

- Name: Bone Density Conservation Agents

- Abbrev: Vi

- Name: Vitamins

- Abbrev: AA

- Name: Amino Acids

### Intervention Browse Module - Browse Leaves

- ID: M8600

- Name: Fluorouracil

- Relevance: LOW

- As Found: Unknown

- ID: M1674

- Name: Oxaliplatin

- Relevance: HIGH

- As Found: Outcomes

- ID: M1671

- Name: Irinotecan

- Relevance: HIGH

- As Found: Infection

- ID: M5381

- Name: Calcium

- Relevance: HIGH

- As Found: Radiation

- ID: M8618

- Name: Folic Acid

- Relevance: LOW

- As Found: Unknown

- ID: M17546

- Name: Vitamin B Complex

- Relevance: LOW

- As Found: Unknown

- ID: M5398

- Name: Calcium, Dietary

- Relevance: LOW

- As Found: Unknown

- ID: M2889

- Name: Tyrosine Kinase Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M9789

- Name: Hormones

- Relevance: LOW

- As Found: Unknown

- ID: M29349

- Name: Topoisomerase I Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M7951

- Name: Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: T447

- Name: Folinic Acid

- Relevance: LOW

- As Found: Unknown

- ID: T446

- Name: Folic Acid

- Relevance: LOW

- As Found: Unknown

- ID: T448

- Name: Folate

- Relevance: HIGH

- As Found: Mitochondrial

- ID: T475

- Name: Vitamin B9

- Relevance: LOW

- As Found: Unknown

- ID: T22

- Name: Tyrosine

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000077150

- Term: Oxaliplatin

- ID: D000077146

- Term: Irinotecan

- ID: D000002118

- Term: Calcium

### Misc Info Module

- Version Holder: 2024-05-24
