Colorectal Cancer MetastaticPhase 3REGTAS-2NCT06992648
Trifluridine/Tipiracil Plus Regorafenib vs Trifluridine/Tipiracil Plus Bevacizumab for Refractory Metastatic Colorectal Cancer
A Phase 3 study testing Trifluridine/Tipiracil + Regorafenib and Trifluridine/tipiracil + bevacizumab in people with Colorectal Cancer Metastatic and Colorectal Cancer Recurrent, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 1 site in China.
Trial summary
The goal of this clinical trial is to demonstrate the non-inferiority of trifluridine/tipiracil + regorafenib vs trifluridine/tipiracil + bevacizumab in terms of progression free survival in patients with refractory metastatic colorectal cancer(mCRC) patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer Metastatic, Colorectal Cancer Recurrent
- What is being tested?
- Trifluridine/Tipiracil + Regorafenib and Trifluridine/tipiracil + bevacizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 302 participants
- Where
- 1 siteChina
- Study dates
- 1 Apr 2025to 31 Dec 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Sign Informed Consent Form (ICF) must be obtained during the screening visit, prior to the performance of any study procedure；
- Male or female patient aged ≥18 years old;
- Has histologically confirmed unresectable adenocarcinoma of the colon or rectum (all other histological types are excluded);
- RAS status must have been previously determined (mutant or wild-type) based on local assessment of tumor biopsy;
- Prior treatment regimens for the treatment of advanced colorectal cancer must have included a fluoropyrimidine, irinotecan, oxaliplatin, an anti-VEGF monoclonal antibody and/or an anti-EGFR monoclonal antibody for RAS wildtype patients;
- Has measurable or non-measurable disease as defined by RECIST version 1.1;
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- Is able to swallow oral tablets;
- Estimated life expectancy ≥12 weeks;
- ECOG PS 0-1；
- Has adequate organ function as defined by the following laboratory values obtained within 7 days prior to randomization:
- Absolute neutrophil count ≥1.5×109/L; Platelet count ≥75×109/L; Hemoglobin≥90g/L (7 days without transfusion); Creatinine clearance ≥60 mL/min, assessed using the Cockcroft \& Gault formula; Total serum bilirubin <1.5×upper limit of normal (ULN) (unless Gilbert disease confirmed); Aspartate aminotransferase (AST; SGOT) and alanine aminotransferase (ALT; SGPT) ≤ 2.5×ULN (unless if liver function abnormalities are due to underlying liver metastasis, AST (SGOT) and ALT (SGPT) ≤ 5×ULN); Urine protein <1+ on urinalysis or 24-hour urine protein <1g; International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5×ULN (For patients receiving anti-coagulant therapy the adequate therapeutic levels of PT should be confirmed).
- Female of childbearing potential must have been tested negative in a serum pregnancy test within 7 days prior to randomization; All patients must agree to use a highly effective method of birth control as well as their partners during the study and lasting at least 6 months after the last dose.
Who cannot join
- Prior trifluridine/tipiracil or TKI regimens for the treatment of advanced colorectal cancer;
- Pregnancy, lactating female or possibility of becoming pregnant during the study;
- Patients currently receiving or having received anticancer therapies within 4 weeks prior to randomization;
- Has not recovered from clinically relevant non-hematologic CTCAE grade ≥ 3 toxicity of previous anticancer therapy prior to randomization (excluding alopecia, and skin pigmentation);
- Has symptomatic central nervous system metastases that are neurologically unstable or requiring increasing doses of steroids to control CNS disease;
- Has severe or uncontrolled active acute or chronic infection;
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- Has active or history of interstitial lung disease and/or pneumonitis, or pulmonary hypertension;
- Has any clinically significant active hepatitis, including but not limited to Hepatitis B or Hepatitis C Virus infection;
- Known carriers of HIV antibodies;
- Confirmed uncontrolled arterial hypertension (defined as systolic blood pressure ≥ 150 mm Hg and/or diastolic blood pressure ≥ 100 mm Hg) or uncontrolled or symptomatic arrhythmia;
- Deep arterial thromboembolic events including cerebrovascular accident or myocardial infarction within the last 6 months prior to randomization;
- Major surgery within 4 weeks prior to randomization (the surgical incision should be fully healed prior to study drug administration), or has not recovered from side effects of previous surgery, or patient that may require major surgery during the study;
- Prior radiotherapy if completed less than 2 weeks before randomization, except if provided as a short course for symptoms palliation only;
- Other clinically significant medical conditions; Other malignancies.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
The Second Affiliated Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310000
About this study
Official title: Trifluridine/Tipiracil Plus Regorafenib vs Trifluridine/Tipiracil Plus Bevacizumab for Refractory Metastatic Colorectal Cancer: A Randomized, Controlled, Open-Label, Non-Inferiority Trial
The goal of this clinical trial is to demonstrate the non-inferiority of trifluridine/tipiracil + regorafenib vs trifluridine/tipiracil + bevacizumab in terms of progression free survival in patients with refractory metastatic colorectal cancer(mCRC) patients. It will also try to estimate the effect of trifluridine/tipiracil + regorafenib vs trifluridine/tipiracil + bevacizumab in terms of OS, ORR, and DCR in patients with refractory mCRC. Other secondary objectives are to compare the safety and tolerance, and the impact on QoL of trifluridine/tipiracil + regorafenib vs trifluridine/tipiracil + bevacizumab in patients with refractory mCRC.
Read the detailed description
This is an investigator-initiated prospective, multicenter, randomized, controlled, open-label, non-inferiority trial evaluating the efficacy and safety of trifluridine/tipiracil + regorafenib vs trifluridine/tipiracil + bevacizumab in patients with refractory mCRC. The study process consists of:
- Screening period. After signing the Informed Consent Form (ICF), patients enter the screening period for eligibility assessments. Test results obtained prior to signing the ICF may be used to evaluate inclusion/exclusion criteria if they meet the requirements, and repeat testing is not required after ICF signing.
- Treatment period. Patients in the experimental arm will receive trifluridine/tipiracil + regorafenib, while those in the control arm will receive trifluridine/tipiracil + bevacizumab. Treatment will continue until the patient experiences disease progression, intolerable toxicity, investigator-determined inability to continue treatment, withdraws the ICF, death or end of study.
- Follow-up period. After the withdrawal visit, a follow-up will be done every 8 weeks±7 days until death, withdrawal the ICF, loss to follow-up or end of study.
- Being tested
- Trifluridine/Tipiracil + Regorafenib, Trifluridine/tipiracil + bevacizumab
- Keywords
- trifluridine/tipiracil, regorafenib, bevacizumab, non-inferiority, refractory metastatic colorectal cancer
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Trifluridine/Tipiracil + RegorafenibDrug
Trifluridine/tipiracil will be administered orally BID at a starting dose of 30 mg per square meter of body-surface area, on days 1 through 5 every 2 weeks. Regorafenib will be administered orally QD at a dose-escalation strategy (80 mg/day, followed by weekly increase of 40 mg to 120 mg/day), if no significant drug-related adverse events occurred and 120 mg/day for 21 days of a 28-day cycle.
Trifluridine/tipiracil + bevacizumabDrug
Trifluridine/tipiracil will be administered orally BID at a starting dose of 35 mg per square meter of body-surface area, on days 1 through 5 every 2 weeks. Bevacizumab, at a dose of 5 mg per kilogram of body weight, will be administered IV every 2 weeks (day 1 and day 15).
| Study group | Role | What they receive |
|---|---|---|
| experimental arm | Experimental | Trifluridine/tipiracil will be administered orally BID at a starting dose of 30 mg per square meter of body-surface area, on days 1 through 5 every 2 weeks. Regorafenib will be administered orally QD at a dose-escalation strategy (80 mg/day, followed by weekly increase of 40 mg to 120 mg/day), if no significant drug-related adverse events occurred and 120 mg/day for 21 days of a 28-day cycle. Receives: Drug: Trifluridine/Tipiracil + Regorafenib |
| Control arm | Active comparator | Trifluridine/tipiracil will be administered orally BID at a starting dose of 35 mg per square meter of body-surface area, on days 1 through 5 every 2 weeks. Bevacizumab, at a dose of 5 mg per kilogram of body weight, will be administered IV every 2 weeks (day 1 and day 15). Receives: Drug: Trifluridine/tipiracil + bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival
The primary objective is to demonstrate the non-inferiority of trifluridine/tipiracil + regorafenib vs trifluridine/tipiracil + bevacizumab in terms of PFS in patients with refractory mCRC
Measured: up to 24 months
Secondary outcomes (3)
Overall survival (OS)
To estimate the effect of trifluridine/tipiracil + regorafenib vs trifluridine/tipiracil + bevacizumab in terms of OS in patients with refractory mCRC.
Measured: up to 36 months
Objective Response Rate（ORR）
To estimate the effect of trifluridine/tipiracil + regorafenib vs trifluridine/tipiracil + bevacizumab in terms of ORR in patients with refractory mCRC.
Measured: up to 36 months
Disease Control Rate（DCR）
To estimate the effect of trifluridine/tipiracil + regorafenib vs trifluridine/tipiracil + bevacizumab in terms of DCR in patients with refractory mCRC.
Measured: up to 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 May 2025
- Study start1 Apr 2025
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal Cancer MetastaticStudies of the same condition, open and under way.
- More trials run by Second Affiliated Hospital, Zhejiang University, School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 302 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ying Yuan, Prof., Principal investigator, Second Affiliated Hospital, Zhejiang University, School of MedicineJing Hao, Prof., Principal investigator, Qilu Hospital of Shandong University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06992648
- Sponsor's protocol ID
- 2024-1454
- Acronym
- REGTAS-2
- Status last verified
- Apr 2025
- First submitted
- 15 Apr 2025
- Last updated
- 28 May 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Trifluridine/Tipiracil Plus Regorafenib vs Trifluridine/Tipiracil Plus Bevacizumab for Refractory Metastatic Colorectal Cancer: A Randomized, Controlled, Open-Label, Non-Inferiority Trial
- ClinicalTrials.gov ID
- NCT06992648
- Acronym / sponsor ID
- REGTAS-2 / 2024-1454
- Keywords
- trifluridine/tipiracil, regorafenib, bevacizumab, non-inferiority, refractory metastatic colorectal cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 302 participants (estimated)
- Lead sponsor
- Second Affiliated Hospital, Zhejiang University, School of MedicineUniversity, hospital or other
- Study start
- 1 Apr 2025 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 28 May 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to demonstrate the non-inferiority of trifluridine/tipiracil + regorafenib vs trifluridine/tipiracil + bevacizumab in terms of progression free survival in patients with refractory metastatic colorectal cancer(mCRC) patients. It will also try to estimate the effect of trifluridine/tipiracil + regorafenib vs trifluridine/tipiracil + bevacizumab in terms of OS, ORR, and DCR in patients with refractory mCRC. Other secondary objectives are to compare the safety and tolerance, and the impact on QoL of trifluridine/tipiracil + regorafenib vs trifluridine/tipiracil + bevacizumab in patients with refractory mCRC.
Detailed description
This is an investigator-initiated prospective, multicenter, randomized, controlled, open-label, non-inferiority trial evaluating the efficacy and safety of trifluridine/tipiracil + regorafenib vs trifluridine/tipiracil + bevacizumab in patients with refractory mCRC. The study process consists of:
- Screening period. After signing the Informed Consent Form (ICF), patients enter the screening period for eligibility assessments. Test results obtained prior to signing the ICF may be used to evaluate inclusion/exclusion criteria if they meet the requirements, and repeat testing is not required after ICF signing.
- Treatment period. Patients in the experimental arm will receive trifluridine/tipiracil + regorafenib, while those in the control arm will receive trifluridine/tipiracil + bevacizumab. Treatment will continue until the patient experiences disease progression, intolerable toxicity, investigator-determined inability to continue treatment, withdraws the ICF, death or end of study.
- Follow-up period. After the withdrawal visit, a follow-up will be done every 8 weeks±7 days until death, withdrawal the ICF, loss to follow-up or end of study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| experimental arm | Experimental | Drug: Trifluridine/Tipiracil + RegorafenibTrifluridine/tipiracil will be administered orally BID at a starting dose of 30 mg per square meter of body-surface area, on days 1 through 5 every 2 weeks. Regorafenib will be administered orally QD at a dose-escalation strategy (80 mg/day, followed by weekly increase of 40 mg to 120 mg/day), if no significant drug-related adverse events occurred and 120 mg/day for 21 days of a 28-day cycle. |
| Control arm | Active comparator | Drug: Trifluridine/tipiracil + bevacizumabTrifluridine/tipiracil will be administered orally BID at a starting dose of 35 mg per square meter of body-surface area, on days 1 through 5 every 2 weeks. Bevacizumab, at a dose of 5 mg per kilogram of body weight, will be administered IV every 2 weeks (day 1 and day 15). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Sign Informed Consent Form (ICF) must be obtained during the screening visit, prior to the performance of any study procedure；
- Male or female patient aged ≥18 years old;
- Has histologically confirmed unresectable adenocarcinoma of the colon or rectum (all other histological types are excluded);
- RAS status must have been previously determined (mutant or wild-type) based on local assessment of tumor biopsy;
- Prior treatment regimens for the treatment of advanced colorectal cancer must have included a fluoropyrimidine, irinotecan, oxaliplatin, an anti-VEGF monoclonal antibody and/or an anti-EGFR monoclonal antibody for RAS wildtype patients;
Key exclusion criteria (14 listed)
- Prior trifluridine/tipiracil or TKI regimens for the treatment of advanced colorectal cancer;
- Pregnancy, lactating female or possibility of becoming pregnant during the study;
- Patients currently receiving or having received anticancer therapies within 4 weeks prior to randomization;
- Has not recovered from clinically relevant non-hematologic CTCAE grade ≥ 3 toxicity of previous anticancer therapy prior to randomization (excluding alopecia, and skin pigmentation);
- Has symptomatic central nervous system metastases that are neurologically unstable or requiring increasing doses of steroids to control CNS disease;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Trifluridine/Tipiracil + RegorafenibTrifluridine/tipiracil will be administered orally BID at a starting dose of 30 mg per square meter of body-surface area, on days 1 through 5 every 2 weeks. Regorafenib will be administered orally QD at a dose-escalation strategy (80 mg/day, followed by weekly increase of 40 mg to 120 mg/day), if no significant drug-related adverse events occurred and 120 mg/day for 21 days of a 28-day cycle. | Drug | experimental arm |
| Trifluridine/tipiracil + bevacizumabTrifluridine/tipiracil will be administered orally BID at a starting dose of 35 mg per square meter of body-surface area, on days 1 through 5 every 2 weeks. Bevacizumab, at a dose of 5 mg per kilogram of body weight, will be administered IV every 2 weeks (day 1 and day 15). | Drug | Control arm |
Primary outcome
Progression free survival
Time frame: up to 24 months
The primary objective is to demonstrate the non-inferiority of trifluridine/tipiracil + regorafenib vs trifluridine/tipiracil + bevacizumab in terms of PFS in patients with refractory mCRC
3 secondary outcomes
Overall survival (OS)
Time frame: up to 36 months
Objective Response Rate（ORR）
Time frame: up to 36 months
Disease Control Rate（DCR）
Time frame: up to 36 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ying Yuan, Prof. principal investigator
Second Affiliated Hospital, Zhejiang University, School of Medicine
Jing Hao, Prof. principal investigator
Qilu Hospital of Shandong University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Trifluridine/Tipiracil + Regorafenib and Trifluridine/tipiracil + bevacizumab in people with Colorectal Cancer Metastatic and Colorectal Cancer Recurrent, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 28 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yinuo TAN, Dr. (+86-13805753262, tan0yi0nuo@zju.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression free survival (time frame: up to 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 May 2025.