## Protocol Section
### Identification Module
**NCT ID:** NCT06427005

**Brief Title:** Fruquintinib Plus S-1 and Raltitrexed (RSF) for mCRC

**Official Title:** Fruquintinib Combined With S-1 and Raltitrexed for Patients With Metastatic Colorectal Cancer Refractory to Standard Therapies: A Phase II Study

#### Organization Study ID Info
**ID:** 2023-71
#### Organization
**Class:** OTHER
**Full Name:** West China Hospital
### Status Module
#### Completion Date
**Date:** 2024-12-30

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-23

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-19

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2024-06-18

**Type:** ESTIMATED

#### Start Date
**Date:** 2023-02-20

**Type:** ACTUAL

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-23
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-19
**Study First Submit QC Date:** 2024-05-19
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** West China Hospital

#### Responsible Party

**Investigator Affiliation:** West China Hospital

**Investigator Full Name:** Meng Qiu

**Investigator Title:** Professor

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Is US Export:** False

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** Based on the FRECO-2 study, Fruquintinib has become one of the standard third-line treatments for advanced colorectal cancer; however, its objective response rate (ORR) remains low. Our previous studies have shown that the combination of raltitrexed and S-1 -/+ bevacizumab is effective and provides a significant survival benefit in patients with metastatic colorectal cancer (mCRC) who are refractory to standard treatments. This study aims to evaluate the efficacy and safety of combining Fruquintinib with S-1 and raltitrexed in these patients.

**Detailed Description:** Conducted at West China Hospital in China, this investigator-initiated, open-label, single-arm, phase II trial included patients with mCRC that had progressed following treatment with fluoropyrimidine, irinotecan, and oxaliplatin, and had at least one measurable lesion. Patients could have previously received anti-EGFR (for tumors with wild-type RAS) and anti-VEGF therapy in the first or second line, including those who had been treated with bevacizumab in two consecutive chemotherapy regimens. Participants received Fruquintinib (5 mg daily for 14 days followed by a 7-day break), oral S-1 (80-120 mg daily for 14 days, followed by a 7-day break), and raltitrexed (3 mg/m² on day 1, with a maximum dose of 5 mg) every 3 weeks. The primary endpoint was the ORR, while secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity.

### Conditions Module

**Conditions:**

- Fruquintinib

- S-1

- Raltitrexed

**Keywords:**

- S-1

- Fruquintinib

- raltitrexed

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

**Intervention Model Description:** Participants received Fruquintinib (5 mg daily for 14 days followed by a 7-day break), oral S-1 (80-120 mg daily for 14 days, followed by a 7-day break), and raltitrexed (3 mg/m² on day 1, with a maximum dose of 5 mg) every 3 weeks.

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 66

**Type:** ESTIMATED

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Participants received Fruquintinib (5 mg daily for 14 days followed by a 7-day break), oral S-1 (80-120 mg daily for 14 days, followed by a 7-day break), and raltitrexed (3 mg/m² on day 1, with a maximum dose of 5 mg) every 3 weeks.

**Intervention Names:**

- Drug: Fruquintinib

- Drug: S-1

- Drug: raltitrexed

**Label:** RSF treatment arm

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- RSF treatment arm

**Description:** Fruquintinib 5 mg daily for 14 days followed by a 7-day break

**Name:** Fruquintinib

**Other Names:**

- Elunate

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- RSF treatment arm

**Description:** S-1 80-120 mg daily for 14 days, followed by a 7-day break

**Name:** S-1

**Other Names:**

- Tegafur,Gimeracil and Oteracil Potassium Capsules

**Type:** DRUG

#### Intervention 3

**Arm Group Labels:**

- RSF treatment arm

**Description:** raltitrexed 3 mg/m² on day 1, with a maximum dose of 5 mg

**Name:** raltitrexed

**Other Names:**

- thymidylate synthase inhibitor

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Objective Response Rate according to Response Evaluation Criteria in Solid Tumors (RECIST) version. 1.1

**Measure:** ORR

**Time Frame:** about a year

#### Secondary Outcomes

**Description:** Disease Control Rate according to Response Evaluation Criteria in Solid Tumors (RECIST) version. 1.1

**Measure:** DCR

**Time Frame:** about a year

**Description:** OS is the time interval from the start of treatment to death due to any reason or lost of follow-up

**Measure:** OS

**Time Frame:** about a year

**Description:** Version 5.0 and AEs leading to dose interruption or discontinuation.

**Measure:** Safety and tolerability

**Time Frame:** about a year

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

1. Age ≥ 18 years, any gender.
2. Patients with metastatic colorectal adenocarcinoma confirmed by pathological histology or cytology.
3. Expected survival time ≥ 12 weeks.
4. ECOG score of 0-2.
5. Previously treated for metastatic colorectal cancer with fluoropyrimidine (allowing intravenous and/or oral fluoropyrimidine formulations, excluding DPD enzyme inhibitors), irinotecan, and oxaliplatin chemotherapy, which failed (treatment failure defined as intolerable adverse reactions, disease progression during treatment, or disease progression within 6 months after completing adjuvant chemotherapy); regardless of prior use of targeted drugs such as cetuximab or bevacizumab.
6. Patients must have an interval of at least 2 weeks since the last chemotherapy (at least 1 week for oral chemotherapy drugs) or more than 4 weeks since the end of radiotherapy, with the study's observable lesions located outside the radiotherapy target area.
7. According to RECIST 1.1 criteria, at least one measurable tumor lesion with a maximum diameter ≥ 1 cm as determined by spiral CT scan.
8. Laboratory test results within 1 week before enrollment must meet the following criteria:

   1. Hemoglobin ≥ 90 g/L; Platelets (PLT) ≥ 75 × 10\^9/L;
   2. White blood cells (WBC) ≥ 3.0 × 10\^9/L; Neutrophils (ANC) ≥ 1.5 × 10\^9/L;
   3. Serum creatinine (Cr) ≤ 1.5 × upper limit of normal (ULN);
   4. Total bilirubin (TBI) ≤ 1.5 × ULN; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN (≤ 5 × ULN if there is liver metastasis).
9. No prior use of raltitrexed or S-1 (or DPD enzyme inhibitors) in the treatment of colorectal cancer.
10. Signed informed consent.

Exclusion Criteria:

1. Patients unable to take oral medications.
2. Patients who have previously been treated with small molecule TKI drugs.
3. Patients with severe hepatic or renal insufficiency, or a recent history of myocardial infarction (within 3 months).
4. Patients with a history of other malignancies within the past five years, except for cured cervical carcinoma in situ and basal cell carcinoma of the skin.
5. Patients with a history of inflammatory bowel disease or extensive colonic resection, ≥50% or extensive small bowel resection with chronic diarrhea, or intestinal obstruction.
6. Patients with severe uncontrolled internal medical conditions or acute infections (fever \> 38°C due to infection).
7. Patients with symptomatic brain or leptomeningeal metastases (unless the patient has been treated for brain or leptomeningeal metastases \> 6 months, with negative imaging results within 4 weeks before study entry, and has stable clinical symptoms related to brain or leptomeningeal metastases at study entry).
8. Patients with clinically significant, uncontrolled pleural effusion or ascites despite clinical intervention.
9. Pregnant or breastfeeding women, or patients of reproductive potential (males or females not in menopause for less than 1 year) unwilling to use contraception.
10. Patients known to be allergic to raltitrexed, S-1, and Fruquintinib or any of their components.
11. Patients deemed unsuitable for participation in this clinical trial by the investigator.

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** qiumeng33@hotmail.com

**Name:** Meng Qiu, MD.

**Phone:** +8618980921776

**Role:** CONTACT

**Contact 2:**

**Email:** lengweibing@wchscu.cn

**Name:** Weibing C Leng, PhD.

**Phone:** +8618980921763

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Chengdu

**Contacts:**

***Contact 1:***

- **Email:** lengweibing@wchscu.cn

- **Name:** Weibing Leng, Ph.D

- **Phone:** +8618980921763

- **Role:** CONTACT

**Country:** China

**Facility:** Sichuan University West China Hospital

**State:** Sichuan

**Status:** RECRUITING

**Zip:** 610044

**Location 2:**

**City:** Chengdu

**Contacts:**

***Contact 1:***

- **Email:** qiumeng33@hotmail.com

- **Name:** Meng Qiu, MD

- **Phone:** 028-85423203

- **Role:** CONTACT

**Country:** China

**Facility:** West China Hospital, Sichuan University

**State:** Sichuan

**Status:** RECRUITING

#### Overall Officials

**Official 1:**

**Affiliation:** Sichuan University

**Name:** Meng Qiu, MD.

**Role:** STUDY_DIRECTOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Intervention Browse Module - Ancestors

- ID: D000000964

- Term: Antimetabolites, Antineoplastic

- ID: D000000963

- Term: Antimetabolites

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000000970

- Term: Antineoplastic Agents

- ID: D000005493

- Term: Folic Acid Antagonists

- ID: D000004791

- Term: Enzyme Inhibitors

### 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: Vi

- Name: Vitamins

### Intervention Browse Module - Browse Leaves

- ID: M8760

- Name: Tegafur

- Relevance: HIGH

- As Found: Carrier

- ID: M252094

- Name: Raltitrexed

- Relevance: HIGH

- As Found: Ophthalmic suspension

- ID: M4281

- Name: Antimetabolites

- Relevance: LOW

- As Found: Unknown

- ID: M8618

- Name: Folic Acid

- Relevance: LOW

- As Found: Unknown

- ID: M17546

- Name: Vitamin B Complex

- Relevance: LOW

- As Found: Unknown

- ID: M8619

- Name: Folic Acid Antagonists

- 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: LOW

- As Found: Unknown

- ID: T475

- Name: Vitamin B9

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000005641

- Term: Tegafur

- ID: C000068874

- Term: Raltitrexed

### Misc Info Module

- Version Holder: 2024-05-31
