What side effects are associated with this type of intervention?

Common treatments for colorectal cancer include VEGFR inhibitors like Fruquintinib, fluoropyrimidines (e.g., fluorouracil), irinotecan, and oxaliplatin. VEGFR inhibitors can cause hypertension, bleeding, proteinuria, and gastrointestinal perforation. Fluoropyrimidines are associated with side effects such as diarrhea, mucositis, and myelosuppression. Irinotecan can cause severe diarrhea and neutropenia, while oxaliplatin is known for causing peripheral neuropathy and myelosuppression. These side effects vary in severity and frequency, and patients should discuss them with their healthcare provider to manage and mitigate risks effectively.

What prior FDA approvals exist?

Several VEGFR inhibitors have been approved by the FDA for the treatment of colorectal cancer. Notably, Bevacizumab, a monoclonal antibody targeting VEGF-A, has been approved for use in combination with chemotherapy for metastatic colorectal cancer. Regorafenib, an oral multi-kinase inhibitor that targets VEGFR, among other kinases, is approved for patients with metastatic colorectal cancer who have been previously treated with other therapies. Additionally, Ziv-aflibercept, a recombinant fusion protein that acts as a decoy receptor for VEGF, is approved for use in combination with FOLFIRI (folinic acid, fluorouracil, and irinotecan) for patients with metastatic colorectal cancer that is resistant to or has progressed following an oxaliplatin-containing regimen.

What other types of research exist?

Promising alternatives to Fruquintinib for colorectal cancer patients include Regorafenib and TAS-102, both of which have been evaluated in phase III trials. Additionally, emerging therapies such as Surufatinib, which targets the VEGF pathway, and other kinase inhibitors like Lenvatinib and Cabozantinib, are also potential options. These alternatives have shown efficacy in clinical trials and may offer new avenues for treatment in 2024.

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Tyrosine Kinase Inhibitor

Fruquintinib for Colorectal Cancer (FRESCO-2 Trial)

Q: What is the mechanism of action of this treatment?

Colorectal cancer treatments often target specific molecular pathways to inhibit tumor growth and spread. VEGFR inhibitors like Fruquintinib block the vascular endothelial growth factor receptor, which is crucial for tumor angiogenesis—the process by which tumors develop their own blood supply. By inhibiting this pathway, VEGFR inhibitors can starve the tumor of nutrients and oxygen, slowing its growth. EGFR inhibitors, such as cetuximab, target the epidermal growth factor receptor, which is involved in cell proliferation and survival. These inhibitors are particularly effective in tumors without RAS mutations. Chemotherapy agents, like oxaliplatin and fluorouracil, work by damaging the DNA of rapidly dividing cells, leading to cell death. Understanding these mechanisms helps in selecting the most effective treatment strategy for colorectal cancer patients, potentially improving outcomes and minimizing side effects.

Phase 3

Waitlist Available

Research Sponsored by Hutchison Medipharma Limited

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Age ≥18 years

Histologically and/or cytologically documented metastatic colorectal adenocarcinoma. RAS, BRAF, and microsatellite instability (MSI)/mismatch repair (MMR) status for each patient must be documented according to country level guidelines

Must not have

Absolute neutrophil count (ANC) <1.5×109/L, platelet count <100×109/L, or hemoglobin <9.0 g/dL. Blood transfusion within 1 week prior to enrollment for the purpose of increasing the likelihood of eligibility is not allowed

Clinically significant cardiovascular disease, including but not limited to acute myocardial infarction or coronary artery bypass surgery within 6 months prior to enrollment, severe or unstable angina pectoris, New York Heart Association Class III/IV congestive heart failure, ventricular arrhythmias requiring treatment, or left ventricular ejection fraction (LVEF) <50% by echocardiogram

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 42 months

Awards & highlights

Pivotal Trial

Summary

This trial tests fruquintinib, a drug that blocks signals making cancer cells grow, in patients with advanced colorectal cancer who haven't responded to other treatments. Fruquintinib is a drug that blocks signals making cancer cells grow and has shown significant benefits in previous trials for certain types of lung cancer. It aims to find new options for those whose cancer continues to progress despite other treatments.

Who is the study for?

This trial is for adults over 18 with metastatic colorectal cancer who've already tried certain treatments like TAS-102 or regorafenib, and standard therapies including chemotherapy and biological therapy. They must weigh at least 40kg, have a performance status of 0-1 indicating they are fully active or restricted in physically strenuous activity but ambulatory, and be expected to live more than 12 weeks.

What is being tested?

The study tests the effectiveness and safety of Fruquintinib plus best supportive care (BSC) compared to a placebo plus BSC in patients with refractory metastatic colorectal cancer. Participants are randomly assigned in a 2:1 ratio to either receive Fruquintinib or a placebo.

What are the potential side effects?

While specific side effects for Fruquintinib aren't listed here, similar medications often cause symptoms like fatigue, nausea, diarrhea, low blood cell counts increasing infection risk, liver issues, mouth sores, loss of appetite and weight changes.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am 18 years old or older.

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My colorectal cancer is confirmed by tests and I know my RAS, BRAF, and MSI/MMR status.

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My body weight is at least 40kg.

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I am fully active or can carry out light work.

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I agree to use effective birth control and an additional barrier method during and after the study.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My blood counts are low and I haven't had a transfusion to improve them in the last week.

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I do not have serious heart problems or recent heart surgery.

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I haven't had a live vaccine in the last 28 days.

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I have a heart condition that affects its electrical activity or a family history of similar issues.

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My blood pressure is controlled and below 140/90 mm Hg with medication.

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I am not pregnant or breastfeeding.

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I have previously taken fruquintinib.

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My urine tests show high protein levels.

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My cancer has spread to a major blood vessel.

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I am HIV positive.

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I don't have severe side effects from past cancer treatments, except for possible hair loss or mild nerve issues.

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I am currently receiving IV antibiotics for an uncontrolled infection.

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I am not taking any medications known to affect heart rhythm.

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My kidney function is below normal levels.

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I haven't taken strong CYP3A4 drugs in the last 2 weeks or more.

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I haven't taken any targeted cancer drugs within the last 4 weeks or 5 half-lives, whichever is shorter.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 42 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 42 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 42 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Overall Survival (OS)

Secondary study objectives

Change From Baseline in EuroQoL 5 Dimension 5 Level (EQ-5D-5L) Health Utility Index Scores

Change From Baseline in EuroQoL 5 Dimension 5 Level (EQ-5D-5L) Visual Analog Scale (VAS) Score

Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life (QOL) Questionnaire Core 30 (EORTC QLQ-C30) Global Health Status/Quality of Life Scale Score

+11 more

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: Fruquintinib Plus Best Supportive Care (BSC) GroupExperimental Treatment1 Intervention

Participants will be orally administered Fruquintinib 5 mg in combination with BSC once daily for 3 weeks of continuous dosing followed by a 1-week break (with each cycle length of 28 days).

Group II: Placebo Plus BSC GroupPlacebo Group1 Intervention

Participants will be orally administered Placebo 5 mg in combination with BSC once daily for 3 weeks of continuous dosing followed by a 1-week break (with each cycle length of 28 days).

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Fruquintinib

2021

Completed Phase 3

~1680

0 / 21Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Colorectal cancer treatments often target specific molecular pathways to inhibit tumor growth and spread. VEGFR inhibitors like Fruquintinib block the vascular endothelial growth factor receptor, which is crucial for tumor angiogenesis—the process by which tumors develop their own blood supply. By inhibiting this pathway, VEGFR inhibitors can starve the tumor of nutrients and oxygen, slowing its growth. EGFR inhibitors, such as cetuximab, target the epidermal growth factor receptor, which is involved in cell proliferation and survival. These inhibitors are particularly effective in tumors without RAS mutations. Chemotherapy agents, like oxaliplatin and fluorouracil, work by damaging the DNA of rapidly dividing cells, leading to cell death. Understanding these mechanisms helps in selecting the most effective treatment strategy for colorectal cancer patients, potentially improving outcomes and minimizing side effects.