## Protocol Section
### Identification Module
**NCT ID:** NCT06434090

**Brief Title:** Liposomal Irinotecan Plus Bevacizumab in Irinotecan-refractory Metastatic Colorectal Cancer

**Official Title:** Liposomal Irinotecan Plus Bevacizumab in Irinotecan-refractory Metastatic Colorectal Cancer:a Multicenter, Phase I/II Trial.

#### Organization Study ID Info
**ID:** CSPC-DEY-CRC-K06
#### Organization
**Class:** OTHER
**Full Name:** Sun Yat-sen University
### Status Module
#### Completion Date
**Date:** 2026-07-01

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-30

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-23

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2025-06-05

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-06-05

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-30
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-23
**Study First Submit QC Date:** 2024-05-23
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Sun Yat-sen University

#### Responsible Party

**Investigator Affiliation:** Sun Yat-sen University

**Investigator Full Name:** Yanhong Deng

**Investigator Title:** Director of Medical Oncology, Clinical Professor

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** To evaluate the efficacy and safety of liposomal irinotecan plus bevacizumab in irinotecan-refractory metastatic colorectal cancer

**Detailed Description:** The standard treatment regimen based on irinotecan with or without bevacizumab is commonly used in metastatic colorectal cancer. With administration of traditional irinotecan, the parent drug and active metabolite SN-38 exist in the form of active lactone and carboxylate, and the lactone ring structure is unstable in neutral and alkaline solutions. In physiological pH conditions, the active lactone rapidly hydrolyzes to the inactive carboxylate, thereby reducing the efficacy, so there is certain limitation in clinical application.

Liposomes Irinotecan load the active substance irinotecan into liposomes, so that it can be slowly released in the body and achieve the effect of reducing toxicity and increasing efficacy.After being rationally designed, irinotecan liposomes can also take advantage of the high permeability and retention effect (EPR) to specifically target the tumor area, increase the amount of drug taken up by cancer cells, reduce the dosage, improve efficacy, and reduce side effects.

We are currently conducting an Phase I/II study in mCRC patients who have previously received irinotecan. After determining the maximum tolerable dose (MTD) of irinotecan liposomes in the combined regimen of irinotecan liposomes and bevacizumab, we will further explore the safety and initial efficacy of irinotecan liposomes combined with bevacizumab.

### Conditions Module

**Conditions:**

- Colorectal Cancer

**Keywords:**

- Liposomal irinotecan

- bevacizumab

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 74

**Type:** ESTIMATED

**Phases:**

- PHASE1

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Patients received Liposomal irinotecan (a '3+3' design was adopted in the experimental arm, with 3 dose levels of 70mg/m2, 80mg/m2, and 90mg/m2 for dose exploration) every 2 weeks (Q2W).

bevacizumab, 5mg/m2, every 2 weeks The two-drug combination therapy was continued every 2 weeks in a cycle until patients developed disease progression or met other criteria for termination of study treatment specified in the protocol.

**Intervention Names:**

- Drug: Liposomal irinotecan

- Drug: Bevacizumab

**Label:** Liposomal irinotecan plus bevacizumab

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Liposomal irinotecan plus bevacizumab

**Description:** Liposomal irinotecan will be given biweekly at a dose from 70mg/m2 to 90mg/m2.

**Name:** Liposomal irinotecan

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Liposomal irinotecan plus bevacizumab

**Description:** bevacizumab will be given biweekly at a dose of 5mg/m2

**Name:** Bevacizumab

**Other Names:**

- avastin

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Defined as the highest dose of DLT in\<33% of subjects .

**Measure:** Maximum tolerated dose (MTD) of liposomal irinotecan

**Time Frame:** 1 months

**Description:** Defined as the proportion of patients who achieved complete response (CR) and partial response (PR) according to RECIST v1.1.

**Measure:** Objective Response Rate

**Time Frame:** 5 months

#### Secondary Outcomes

**Description:** Defined as adverse events that occur during the DLT observation period and are related to the study drug .

**Measure:** Dose-Limiting Toxicities (DLT) of liposomal irinotecan

**Time Frame:** 1 months

**Description:** Defined as the proportion of patients who achieved complete response (CR), partial response (PR), and stable disease (SD) according to RECIST v1.1.

**Measure:** Disease Control Rate

**Time Frame:** 5 months

**Description:** Defined as the time from response(when CR or PR is first diagnosed) to disease progression or death due to any cause.

**Measure:** Duration of Response

**Time Frame:** 5 months

**Description:** Defined as the time between signing the informed consent form to the disease progression (according to RECIST v1.1 criteria) or death due to any cause.

**Measure:** Progression free Survival

**Time Frame:** 1 years

**Description:** Defined as the time between signing the informed consent form to death due to various causes.

**Measure:** Overall survival

**Time Frame:** 1 years

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

1. Age: ≥18 years old；
2. Histopathologically and/or cytologically confirmed unresectable metastatic colorectal adenocarcinoma；
3. Previous treatment with irinotecan , and have progression of disease during treatment or within three months thereafter；
4. At least one measurable lesion (according to RECIST v1.1)；
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 \~ 1；
6. The expected survival time ≥3 months；
7. Adequate bone marrow function : no blood transfusion and/or use of increasing leukocyte drugs (excluding oral medication) within 14 days prior to enrollment Absolute neutrophil count (ANC) ≥1.5×109/L Platelet count ≥100×109/L Hemoglobin (Hgb) ≥90 g/L；
8. Adequate hepatic function as evidenced by:

Total bilirubin ≤1.5 × upper limit of normal (ULN), Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN, ≤5 × ULN if liver metastases are present.

Serum albumin ≥30 g/L； (9Adequate renal function as evidenced by: serum creatinine (Cr) ≤1.5 × ULN or creatinine clearance ≥60 mL/min. proteinuria\<2+（those with proteinuria ≥2+ at baseline had to demonstrate ≤1 g protein per 24 hours）； (10)Coagulation function: International normalised ratio (INR) ≤1.5, activated partial thromboplastin time (APTT) ≤1.5 × ULN； (11)Agree and be able to comply with the plan during the study period. Provide written informed consent before entering the study screening；

Exclusion Criteria:

1. Any other malignancy within 5 years, with the exception of cured in-situ carcinoma or basal cell carcinoma etc；
2. Patients with the primary lesion located in the left colon and RAS/BRAF wild-type who did not use cetuximab on the first-line；
3. Patients with high microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR)；
4. Massive pleural effusion or ascites requiring intervention；
5. Active, uncontrolled bacterial, viral, or fungal infections that require systemic treatment；
6. Active HIV infection；
7. Combined with uncontrollable systemic diseases within 6 months before the first administration；
8. Presence of severe gastrointestinal disease；
9. History of major surgery (such as laparotomy, thoracotomy or intestinal resection) within 28 days before the first administration,or plan to undergo major surgery during the study period；
10. Presence of interstitial pneumonia or pulmonary fibrosis；
11. History of allergy or hypersensitivity to drug or any of their excipients；
12. History of pulmonary hemorrhage/hemoptysis ≥Grade 2 (defined as bright red blood of at least 2.5mL) within one month before the first administration；
13. Presence of arterial embolism, severe bleeding (excluding bleeding caused by surgery) or tendency for existing embolism or severe bleeding within 6 months before the first administration；
14. Combined symptomatic brain metastasis, meningeal metastasis, spinal cord tumor invasion, and spinal cord compression syndrome；
15. Use of strong inhibitors or inducers of CYP3A, CYP2C8 and UGT1A1 within 14 days before the first administration；
16. Participate in other study and use study drug within 1 month or within 5 half-lives of the drug (whichever comes first) before the first administration；
17. Pregnant or breastfeeding women, or subjects of childbearing age who refuse contraception；
18. Patients who are not suitable to participate in this trial for any reason judged by the investigator；

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** dengyanh@mail.sysu.edu.cn

**Name:** Yanhong Deng, PhD

**Phone:** 020-38379762

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Guangzhou

**Contacts:**

***Contact 1:***

- **Email:** dengyanh@mail.sysu.edu.cn

- **Name:** Yanghong Deng, Phd

- **Phone:** 02038379762

- **Role:** CONTACT

**Country:** China

**Facility:** The Sixth Affiliated Hospital of Sun Yat-sen University

**State:** Guangdong

**Zip:** 510655

#### Overall Officials

**Official 1:**

**Affiliation:** Sixth Affiliated Hospital, Sun Yat-sen University

**Name:** Yanhong Deng, PhD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## 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: M8883

- Name: Gastrointestinal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M7255

- Name: Digestive System 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: D000074322

- Term: Antineoplastic Agents, Immunological

- ID: D000000970

- Term: Antineoplastic Agents

- ID: D000020533

- Term: Angiogenesis Inhibitors

- ID: D000043924

- Term: Angiogenesis Modulating Agents

- ID: D000006133

- Term: Growth Substances

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000006131

- Term: Growth Inhibitors

- 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

### Intervention Browse Module - Browse Leaves

- ID: M1671

- Name: Irinotecan

- Relevance: HIGH

- As Found: Infection

- ID: M246

- Name: Bevacizumab

- Relevance: HIGH

- As Found: Non-

- ID: M1346

- Name: Antineoplastic Agents, Immunological

- Relevance: LOW

- As Found: Unknown

- ID: M22318

- Name: Angiogenesis Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M9231

- Name: Growth Inhibitors

- 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

### Intervention Browse Module - Meshes

- ID: D000068258

- Term: Bevacizumab

- ID: D000077146

- Term: Irinotecan

### Misc Info Module

- Version Holder: 2024-05-31
