Fruquintinib for Colorectal Cancer

Recruiting at37 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: Takeda

Must not be taking: Anticoagulants, TKIs, CYP3A4 inducers

Disqualifiers: Uncontrolled hypertension, Cardiovascular disease, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

High blood pressure (hypertension) is a known side effect of the treatment with fruquintinib. Current research does not provide a clear answer whether minority groups such as Black/African American and/or Hispanic/Latino with refractory metastatic colorectal cancer (mCRC) have a bigger risk of higher blood pressure after treatment with fruquintinib. The main aim of this study is to learn how often adults of a minority group experience hypertension after they have been treated with fruquintinib for refractory mCRC. Other aims are to learn how safe fruquintinib is and how well it is tolerated by participants. Participants will receive fruquintinib in 4-week treatment cycles until their condition worsens, they do no longer tolerate the treatment or stop the treatment for other reasons. After the last treatment, participants will be checked upon every 3 months until study completion.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot use certain therapies like systemic antineoplastic therapies or strong inducers of CYP3A4 within a specified period before starting the trial.

What data supports the effectiveness of the drug Fruquintinib for colorectal cancer?

Fruquintinib has been shown to be effective in treating metastatic colorectal cancer, especially in patients who have not responded to other treatments. It works by blocking certain proteins (VEGFRs) that help cancer cells grow and spread, and has been approved for use in China for this purpose. ^{1 2 3 4 5}

Is fruquintinib safe for humans?

Fruquintinib has been studied in patients with metastatic colorectal cancer and has shown an acceptable safety profile. Common side effects include hand-foot skin reaction, fatigue, and mouth sores, but these were generally manageable. ^{1 6 7 8 9}

What makes the drug Fruquintinib unique for treating colorectal cancer?

Fruquintinib is unique because it is a highly selective oral drug that targets specific proteins (VEGFR1, 2, and 3) involved in blood vessel growth, which is crucial for cancer development. It is particularly used for patients with metastatic colorectal cancer who have not responded to other treatments, offering a new option with low off-target toxicity and good tolerance. ^{1 2 5 10 11}

Research Team

Study Director

Principal Investigator

Takeda

Eligibility Criteria

This trial is for adults over 18 who self-identify as Black/African American or Hispanic/Latino with advanced colorectal cancer that has spread and didn't respond to standard treatments. They must be able to perform daily activities with ease (ECOG status 0-1) and weigh at least 40 kg. Participants need documented RAS status, have tried specific chemotherapies and biological therapies, and if applicable, PD1 inhibitors or anti-EGFR therapy.

Inclusion Criteria

I weigh at least 40 kg.

I am fully active or can carry out light work.

My cancer is RAS wild-type and suitable for anti-EGFR therapy like cetuximab.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive fruquintinib in 4-week treatment cycles until progressive disease, unacceptable toxicity, or other discontinuation criteria are met

Variable (until progression or discontinuation)

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with checks every 3 months until study completion

Approximately 35 months

Quarterly visits (in-person)

Treatment Details

Interventions

• Fruquintinib (Tyrosine Kinase Inhibitor)

Trial Overview The study tests the safety and effect of Fruquintinib on blood pressure in minority populations with metastatic colorectal cancer resistant to previous treatments. Patients will take Fruquintinib in cycles of four weeks until their disease progresses, side effects become intolerable, or they choose to stop treatment.

Participant Groups

Group I: Fruquintinib 5 mg Experimental Treatment 1 Intervention

Participants will receive fruquintinib capsule at a dose of 5 mg, orally (PO), once daily (QD), for the first 21 days of each 28-day treatment cycle until progressive disease (PD), unacceptable toxicity, or other discontinuation criteria are met.

Who Is Running the Clinical Trial?

Takeda

Lead Sponsor

Trials

1,255

Recruited

4,219,000+

Dr. Naoyoshi Hirota

Takeda

Chief Medical Officer since 2020

MD from University of Tokyo

Christophe Weber

Takeda

Chief Executive Officer since 2015

PhD in Molecular Biology from Université de Montpellier

Findings from Research

Fruquintinib is a highly selective oral inhibitor of VEGFR1, 2, and 3 tyrosine kinases, effectively blocking VEGF-induced signaling that promotes cancer cell growth and blood vessel formation.

It has been approved in China for treating metastatic colorectal cancer in patients who have not responded to at least two previous therapies, although it is not yet approved in other countries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fruquintinib and its use in the treatment of metastatic colorectal cancer. Deng, Y., Li, X.[2022]

Fruquintinib is a selective tyrosine kinase inhibitor targeting VEGF receptors, approved in China for metastatic colorectal cancer, and is currently being tested in the global FRESCO-2 Phase III study involving approximately 687 patients.

The study aims to evaluate the efficacy and safety of fruquintinib compared to placebo, focusing on overall survival and progression-free survival in patients who have not responded to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FRESCO-2: a global Phase III study investigating the efficacy and safety of fruquintinib in metastatic colorectal cancer. Dasari, A., Sobrero, A., Yao, J., et al.[2022]

Fruquintinib, a VEGFR inhibitor, significantly improved progression-free survival (PFS) by 3.7 months in metastatic colorectal cancer patients compared to placebo, demonstrating its efficacy in treatment-refractory cases.

The safety profile of fruquintinib was consistent with other VEGFR tyrosine kinase inhibitors, with common severe side effects including hypertension and hand-foot skin reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of fruquintinib in patients with previously treated metastatic colorectal cancer: a phase Ib study and a randomized double-blind phase II study. Xu, RH., Li, J., Bai, Y., et al.[2022]

In a study of 45 patients with refractory metastatic colorectal cancer (mCRC), the combination of fruquintinib and various PD-1 inhibitors showed clinical activity, with an overall response rate of 11.1% and a disease control rate of 62.2%.

The median overall survival was 14.9 months, and no adverse-effect-related deaths were reported, suggesting that this treatment combination is safe for heavily pretreated patients, although further research is needed to confirm these findings in larger populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fruquintinib in Combination With PD-1 Inhibitors in Patients With Refractory Non-MSI-H/pMMR Metastatic Colorectal Cancer: A Real-World Study in China. Gou, M., Qian, N., Zhang, Y., et al.[2022]

In the FRESCO trial involving Chinese patients with metastatic colorectal cancer, fruquintinib showed a significant overall survival benefit, with 95.7% of patients experiencing at least one treatment-related adverse event (TEAE).

The most common severe treatment-related adverse events (grade ≥3) included hypertension (21.2%), hand-foot skin reaction (10.8%), and proteinuria (3.2%), with similar frequencies observed across different age, sex, and BMI subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Profile and Adverse Events of Special Interest for Fruquintinib in Chinese Patients with Previously Treated Metastatic Colorectal Cancer: Analysis of the Phase 3 FRESCO Trial. Li, J., Guo, W., Bai, Y., et al.[2022]

Regorafenib and fruquintinib are effective and well-tolerated third-line treatment options for metastatic colorectal cancer (mCRC), as supported by a review of clinical studies.

Both drugs have similar survival outcomes, but regorafenib demonstrates a slightly better toxicity profile, making it a preferable choice in terms of safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of regorafenib and fruquintinib as third-line treatment for colorectal cancer: a narrative review. Xu, X., Yu, Y., Liu, M., et al.[2022]

In a real-world study of 75 patients with metastatic colorectal cancer, fruquintinib demonstrated a median progression-free survival of 5.4 months, indicating its efficacy as a treatment option.

The treatment was generally safe, with only 6% of patients experiencing grade 3 adverse events, which included manageable side effects like hand-foot skin reaction and fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Data: Fruquintinib in Treating Metastatic Colorectal Cancer. Liu, S., Lu, L., Pan, F., et al.[2022]

In the FRESCO study, fruquintinib significantly improved overall survival (OS) and progression-free survival (PFS) in metastatic colorectal cancer patients, regardless of whether they had prior targeted therapy (PTT).

The safety profile of fruquintinib was consistent across both subgroups, with similar rates of treatment-emergent adverse events (TEAEs), indicating that it is a well-tolerated option for patients with or without prior targeted treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subgroup analysis by prior anti-VEGF or anti-EGFR target therapy in FRESCO, a randomized, double-blind, Phase III trial. Xu, R., Qin, S., Guo, W., et al.[2022]

In a study of 366 patients with metastatic colorectal cancer, regorafenib and fruquintinib showed similar efficacy in terms of time-to-treatment failure and overall survival, indicating that both treatments are viable options for patients.

Patients who received regorafenib followed by fruquintinib had a longer overall survival (28.1 months) compared to those who received the treatments in the reverse order (18.4 months), suggesting a potential benefit in treatment sequencing that warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety Comparison of Regorafenib and Fruquintinib in Metastatic Colorectal Cancer-An Observational Cohort Study in the Real World. Zhang, Q., Chen, M., Wang, Z., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Fruquintinib versus placebo in patients with refractory metastatic colorectal cancer (FRESCO-2): an international, multicentre, randomised, double-blind, phase 3 study. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Fruquintinib and its use in the treatment of metastatic colorectal cancer. [2022]

3. England pubmed.ncbi.nlm.nih.gov

FRESCO-2: a global Phase III study investigating the efficacy and safety of fruquintinib in metastatic colorectal cancer. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of fruquintinib in patients with previously treated metastatic colorectal cancer: a phase Ib study and a randomized double-blind phase II study. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Fruquintinib in Combination With PD-1 Inhibitors in Patients With Refractory Non-MSI-H/pMMR Metastatic Colorectal Cancer: A Real-World Study in China. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Safety Profile and Adverse Events of Special Interest for Fruquintinib in Chinese Patients with Previously Treated Metastatic Colorectal Cancer: Analysis of the Phase 3 FRESCO Trial. [2022]

7. China pubmed.ncbi.nlm.nih.gov

Efficacy and safety of regorafenib and fruquintinib as third-line treatment for colorectal cancer: a narrative review. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Real-World Data: Fruquintinib in Treating Metastatic Colorectal Cancer. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Subgroup analysis by prior anti-VEGF or anti-EGFR target therapy in FRESCO, a randomized, double-blind, Phase III trial. [2022]

10. England pubmed.ncbi.nlm.nih.gov

The clinical application of fruquintinib on colorectal cancer. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety Comparison of Regorafenib and Fruquintinib in Metastatic Colorectal Cancer-An Observational Cohort Study in the Real World. [2022]