Safety and Efficacy of Fruquintinib+FOLFIRI in RAS-mutated Metastatic Colorectal Cancer

NCT05522738 | Unknown Phase 1

• 1 other identifier: HMPL-013-N1-CRC104
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

Molecular subtypes make difference on clinicopathologic features and response to chemotherapy and targeted agents as well as prognosis. RAS mutation status, which accounting for approximately 35% to 40% of colorectal cancer patients, is an important factor considered in the standard of care for colorectal cancer. For RAS-mutated patients, no targeted driver gene drugs have been approved, and their treatment is based on the anti-VEGF/VEGFR pathway, and corresponding targeted drugs such as bevacizumab, aflibercept, and ramucirumab have also been successfully marketed for the treatment of CRC. For RAS mutant metastatic colorectal cancer, the commonly used first-line treatment regimen is bevacizumab combined with chemotherapy, which is shown in previous studiesthat the PFS of 1st-line is about 10 months; the standard regimen of second-line treatment is FOLFIRI ± bevacizumab, which is shown in previous study that the 2nd-line PFS is about 5 months with ORR 4%. There are a lot of unmet medical needs to improve the clinical efficacy in secondline-treatment of RAS-mutant patients.

Conditions

Metastatic Colorectal Cancer

Keywords

RAS-mutant; second-line

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate

  Tumor assessment will be performed using radiography method every 8 weeks until the occurrence of progressive disease (PD), using RECIST v 1.1

  From treatment initiation to progressive disease or EOT due to any cause, assessed up to 1 year

• RP2D

  RECIST v1.1

  from first dose up to progressive disease or EOT due to any cause, assessed up to 1 year

Secondary Outcomes (5)

• Overall Survival

  from treatment initiation until death due to any cause, assessed up to 3 year

• Progress-Free Survival

  from treatment initiation until death due to any cause, assessed up to 2 year

• Duration of Response

  from treatment initiation until death due to any cause, assessed up to 2 year

• Safety and tolerance evaluated by incidence of AE

  from first dose to 30 days post the last dose

• Safety and tolerance evaluated by incidence of SAE

  from first dose to 30 days post the last dose

Study Arms (1)

study group

EXPERIMENTAL

Fruquintinib combined with FOLFIRI

Drug: Combination: Fruquintinib + FOLFIRI

Interventions

Combination: Fruquintinib + FOLFIRI DRUG

Phase 1b Fruquintinib was administered in a 3 + 3 dose escalation regimen at the following doses: L1:3 mg/d, L2:4 mg/d, L3:5 mg/d. Fruquintinib: QD po q2w FOLFIRI regimen: Irinotecan：180 mg/m2, i.v. , d1, q2w LV：200 mg/m2, i.v., d1, q2w 5-FU：2400 mg/m2, i.v.for over 46 hours, q2w Phase II Fruquintinib: RP2D, QD po q2w FOLFIRI regimen: Irinotecan： 180 mg/m2, i.v. , d1, q2w LV： 200 mg/m2, i.v., d1, q2w 5-FU：2400 mg/m2, i.v.for over 46 hours, q2w

Also known as: Elunate, HMPL-013

study group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Fully understand the study and voluntarily sign the informed consent form;
• Age ≥ 18 years;
• Pathologically confirmed unresectable metastatic colorectal cancer;
• Known RAS gene mutations;
• failed standard first-line FOLFOX/XELOX combined with bevacizumab;
• ECOG performance status 0-1;
• BMI ≥ 18;
• Expected survival ≥ 3 months;
• Vital organ function meets the following requirements (any blood components and cell growth factors are not allowed within 14 days before enrollment):
• Absolute neutrophil count ≥ 1.5 × 109/L and white blood cells ≥ 4.0 × 109/L;
• Platelets ≥ 100 x 109/L;
• Hemoglobin ≥ 90 g/L;
• Total bilirubin TBIL ≤ 1.5 × ULN;
• ALT and AST ≤ 5 x ULN;
• Urea nitrogen/urea nitrogen (BUN) and creatinine (Cr) ≤ 1.5 x ULN (and creatinine clearance (CCr) ≥ 50 mL/min);

You may not qualify if:

• Unable to comply with the study protocol or study procedures;
• Known BRAF gene mutations;
• evidence of central nervous system metastasis, or associated with severe malignant pleural effusion and ascites;
• Previous treatment with irinotecan;
• previous treatment with VEGFR inhibitor
• Concurrent use of any other investigational drug, or enrollment in a clinical trial of other investigational drug therapy within 4 weeks before enrollment;
• Inactivated vaccines within 4 weeks before enrollment or possibly during the study;
• patients in the study group underwent major surgery or severe traumatic injury, fracture or ulcer within 4 weeks;
• Receiving blood transfusion therapy, blood products and hematopoietic factors, such as albumin and granulocyte colony-stimulating factor (G-CSF), within 28 days before enrollment;
• Alcohol or drug abuse within 4 weeks prior to enrollment;
• Any factor affecting oral administration;
• Concurrent any of the following: uncontrolled hypertension, coronary artery disease, arrhythmia, and heart failure;
• Uncontrollable serious concurrent infections resulting in disability;
• Proteinuria ≥ 2 + (1.0 g/24 h)
• Evidence or history of bleeding tendency within 2 months before enrollment, regardless of seriousness;

Sponsors & Collaborators

• Chinese PLA General Hospital: lead
• Hutchison Medipharma Limited: collaborator

Study Sites (1)

Chinese PLA General Hospital

Beijing, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

HMPL-013

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Guanghai Dai, Doctor

  Chinese PLA General Hospital

  PRINCIPAL INVESTIGATOR

• Quanli Han, Doctor

  Chinese PLA General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Medical Oncology Department

Study Record Dates

• First Submitted: August 23, 2022
• First Posted: August 31, 2022
• Study Start: August 10, 2022
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2025
• Last Updated: January 8, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)