Metastatic Colorectal CancerPhase 2NCT05970705
Regorafenib Combined With TAS-102 Versus Regorafenib Monotherapy in Third or Later Line Therapy of mCRC
A Phase 2 study testing Regorafenib and Trifluridine/Tipiracil in people with Metastatic Colorectal Cancer, run by Fudan University at 1 site in China.
Trial summary
The purpose of this study is to evaluate the clinical benefit of regorafenib combined with TAS-102 compared with regorafenib monotherapy in patients with metastatic colorectal cancer who have failed at least two lines of treatment, to explore the rationality of this combination therapy strategy and to obtain relevant… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- Regorafenib and Trifluridine/Tipiracil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 101 participants
- Where
- 1 siteChina
- Study dates
- 1 Jul 2023to 4 Jul 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- The subjects must meet all of the following criteria to be eligible for this study:
- Patients with histologically confirmed recurrent/metastatic colorectal adenocarcinoma.
- Patients who have failed at least one prior standard first- or second-line therapy, including fluoropyrimidine-based therapy, oxaliplatin, irinotecan, and bevacizumab. Treatment failure is defined as either radiographic evidence of disease progression or unacceptable toxicity during treatment or within three months following completion of therapy.
- (Note: a. each line of therapy should include at least one or more chemotherapy agents administered for at least one cycle; b. adjuvant/neoadjuvant therapy is allowed. If relapse or metastasis occurs during or within six months after completion of adjuvant/neoadjuvant therapy, it is considered a failure of first-line chemotherapy for progressive disease. c. For patients with RAS/RAF wild-type tumors, the use of an EGFR inhibitor is not required.)
- At least one measurable lesion, with the longest diameter ≥10 mm on spiral CT or ≥20 mm on conventional CT (RECIST 1.1 criteria).
- ECOG performance status of 0-2.
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- Life expectancy of ≥12 weeks.
- Adequate bone marrow, hepatic, and renal function measured within the screening period prior to randomization: absolute neutrophil count (ANC) ≥1.5 × 109 /L, hemoglobin ≥ 8.0 g/dL, platelet count ≥ 75 × 109 /L, total bilirubin <1.5 × ULN, ALT and AST <2.5 × ULN (≤5 × ULN for patients with liver involvement), serum creatinine ≤1.5 × ULN, and creatinine clearance ≥50 mL/min.
- Women of childbearing potential must use effective contraception.
- Voluntarily participating in this study, signing the informed consent form, understanding the purpose of the study and the necessary procedures, and willing to participate in this study.
Who cannot join
- Patients who meet any of the following criteria will be excluded from the study:
- Proteinuria ≥2+ on dipstick or 24-hour urinary protein ≥1.0 g/24 h.
- Abnormal coagulation function (PT>16s, APTT>43s, TT>21s, Fbg<2g/L), bleeding tendency, or receiving thrombolysis or anticoagulation therapy.
- Patients at risk of gastrointestinal bleeding, including those with active digestive ulcers and fecal occult blood (++) and those with histories of black stools or hematemesis within three months.
- Receiving systemic antitumor therapy, including chemotherapy, signal transduction inhibitors, or immune therapies, within three weeks prior to screening.
- Patients with uncontrolled hypertension (systolic blood pressure >140 mmHg, diastolic blood pressure >90 mmHg) despite antihypertensive medication, grade I or higher coronary heart disease, grade I or higher arrhythmia (including QTc interval prolongation with ≥450 ms for men and ≥470 ms for women), or grade I or higher heart failure.
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- Patients with a history of thrombotic or embolic events requiring treatment within the preceding six months.
- Patients who have received radiation therapy targeting the selected target lesion.
- Symptomatic brain or meningeal metastasis.
- Uncontrolled pleural or peritoneal effusion.
- Receiving kidney dialysis.
- Serious or uncontrolled infection.
- Pregnant or lactating women or women of childbearing potential without adequate contraception.
- Multiple factors affecting oral drug administration (dysphagia, chronic diarrhea, and bowel obstruction).
- Patients who have been treated with small molecule tyrosine kinase inhibitors containing VEGFR (such as apatinib, fruquintinib, anlotinib, and lenvatinib).
- Patients who have been treated with TAS-102.
- Participation in another clinical study within four weeks prior to screening.
- Patients with comorbidities that could seriously endanger patients' safety or affect their completion of the study.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Fudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality, 200032
Chenchen Wang, M.D, 862154561523, wccnancy2003@aliyun.com
Weijian Guo, M.D
About this study
Official title: A Randomized, Controlled, Multicenter Phase II Trial of Regorafenib Combined With Trifluridine/Tipiracil Versus Regorafenib Monotherapy in Patients With Metastatic Colorectal Cancer Who Failed at Least Two Lines of Systematic Therapy
The purpose of this study is to evaluate the clinical benefit of regorafenib combined with TAS-102 compared with regorafenib monotherapy in patients with metastatic colorectal cancer who have failed at least two lines of treatment, to explore the rationality of this combination therapy strategy and to obtain relevant survival and safety data.
Read the detailed description
Based on the current diagnostic and treatment guidelines, regorafenib and TAS-102 monotherapy are both standard third-line treatment options for patients with metastatic colorectal cancer (mCRC), yet the overall treatment sequence or preference is not clear. A retrospective study directly compared the efficacy of regorafenib and TAS-102 monotherapy for third-line treatment of mCRC, and found similar efficacy between the two treatments. However, the benefits of current third-line monotherapy for mCRC are still limited. Patients who receive oral regorafenib monotherapy have an ORR of less than 5%, disease control rate of 50-60%, and TAS-102 has an ORR of 1.1%-1.6% and a disease control rate of less than 50% in third-line treatment of mCRC. These drugs have limited prolongation of progression-free survival (PFS), and disease progression and drug resistance often occur shortly after medication use. Most mCRC patients have a high tumor burden during third-line treatment, and how to improve the remission rate of treatment, improve patients' quality of life due to high tumor burden, increase disease control, and further bring better survival benefits is still a big challenge for third-line treatment. Regorafenib and TAS-102 have different mechanisms of action and different adverse reaction spectra. When the two drugs are used in combination, they may complement each other in terms of efficacy and are also less likely to have toxic effects.
In the RECOURSE study, 17% of patients in the TAS-102 treatment group had received prior treatment with regorafenib. Subgroup analysis showed that the efficacy of TAS-102 was not dependent on whether or not the patient had previously received regorafenib treatment. Therefore, the combination of regorafenib and TAS-102 may be a valuable treatment option for refractory mCRC. However, there is little clinical research data on whether the combination therapy could further improve efficacy and prolong patient survival compared to monotherapy. In 2021, a phase Ib small-sample study from Germany explored the combined use of regorafenib and TAS-102 in third-line treatment of mCRC. The study included 12 patients who received combined treatment with regorafenib and TAS-102 in third-line treatment. After a 3+3 dose-exploration trial, three cases of DLT were all grade 3 hypertension related to regorafenib. The combination of TAS-102 25 mg/m2 twice daily and regorafenib 120 mg was well tolerated, with a median PFS of 3.81 months (95% CI: 1.51-5.2), and a median OS of 11.1 months (95% CI: 2.3-18.2). The results of this early-phase clinical trial suggest that compared to regorafenib monotherapy in the CORRECT study with a median PFS of less than two months and a median OS of less than seven months, the third-line combination treatment of regorafenib and TAS-102 may potentially provide patients with greater clinical benefits. In conclusion, the combination therapy of regorafenib and TAS-102 may be further explored and studied for late-stage colorectal cancer in third-line or after third-line treatment.
The aim of this study is to evaluate the clinical benefits and safety of the combination of regorafenib and TAS-102 compared to regorafenib monotherapy in patients with advanced colorectal cancer who have failed second-line or later treatments. The efficacy and safety of the combination therapy will be fully evaluated, and explorations of efficacy, PFS, OS, safety, and related biomarkers associated with the combined treatment of regorafenib and TAS-102 will be conducted.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- Regorafenib, Trifluridine/Tipiracil
- Keywords
- metastatic colorectal cancer, regorafenib, TAS-102, Trifluridine/Tipiracil
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RegorafenibDrug
Also called Stivaga
this anti-angiogenesis targeting drug is one of the standard third-line treatment options for patients with metastatic colorectal cancer
Trifluridine/TipiracilDrug
Also called TAS-102
this chemotherapeutic drug is also one of the standard third-line treatment options for patients with metastatic colorectal cancer
| Study group | Role | What they receive |
|---|---|---|
| A: Regorafenib+TAS-102 combination therapy | Experimental | Regorafenib 80mg ,orally, once a day, d1-28, every 28 days, TAS-102，35mg/m2, orally，twice a day, d1-5 \& d15-19，every 28 days Receives: Drug: Regorafenib; Drug: Trifluridine/Tipiracil |
| B：Regorafenib monotherapy | Active comparator | Regorafenib, 120mg orally, once a day, d1-21, every 28 days (If the patient's body surface area is less than 1.5m2, the starting dose of regorafenib is 80mg) Receives: Drug: Regorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
PFS
progression free survival
Measured: from the time signing of ICF until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
Secondary outcomes (4)
OS
overall survival
Measured: from the time signing of ICF until the date of death from any cause, assessed up to 36 months
ORR
objective response rate
Measured: the rate of patients with CR and PR, through study completion, an average of 1 year
DCR
disease control rate
Measured: the rate of patients with CR, PR and SD, through study completion, an average of 1 year
DOR
duration of response
Measured: the time between the first tumor evaluation for CR or PR and the first evaluation for PD(Progressive Disease) or death from any cause, assessed 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 posted1 Aug 2023
- Study start1 Jul 2023
- Primary completion4 Jul 2025 (estimated)
- Study completion4 Jul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Fudan UniversityThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- controlled, randomized
- Masking
- None (open label)
- Enrolment
- 101 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fudan University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Weijian Guo, Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05970705
- Sponsor's protocol ID
- FDZL-REGOT
- Status last verified
- Jul 2023
- First submitted
- 3 Jul 2023
- Last updated
- 1 Aug 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Controlled, Multicenter Phase II Trial of Regorafenib Combined With Trifluridine/Tipiracil Versus Regorafenib Monotherapy in Patients With Metastatic Colorectal Cancer Who Failed at Least Two Lines of Systematic Therapy
- ClinicalTrials.gov ID
- NCT05970705
- Acronym / sponsor ID
- FDZL-REGOT
- Conditions
- Metastatic Colorectal Cancer
- Keywords
- metastatic colorectal cancer, regorafenib, TAS-102, Trifluridine/Tipiracil
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 101 participants (estimated)
- Lead sponsor
- Fudan UniversityUniversity, hospital or other
- Study start
- 1 Jul 2023 (actual)
- Primary completion
- 4 Jul 2025 (estimated)
- Study completion
- 4 Jul 2026 (estimated)
- First posted
- 1 Aug 2023 (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 purpose of this study is to evaluate the clinical benefit of regorafenib combined with TAS-102 compared with regorafenib monotherapy in patients with metastatic colorectal cancer who have failed at least two lines of treatment, to explore the rationality of this combination therapy strategy and to obtain relevant survival and safety data.
Detailed description
Based on the current diagnostic and treatment guidelines, regorafenib and TAS-102 monotherapy are both standard third-line treatment options for patients with metastatic colorectal cancer (mCRC), yet the overall treatment sequence or preference is not clear. A retrospective study directly compared the efficacy of regorafenib and TAS-102 monotherapy for third-line treatment of mCRC, and found similar efficacy between the two treatments. However, the benefits of current third-line monotherapy for mCRC are still limited. Patients who receive oral regorafenib monotherapy have an ORR of less than 5%, disease control rate of 50-60%, and TAS-102 has an ORR of 1.1%-1.6% and a disease control rate of less than 50% in third-line treatment of mCRC. These drugs have limited prolongation of progression-free survival (PFS), and disease progression and drug resistance often occur shortly after medication use. Most mCRC patients have a high tumor burden during third-line treatment, and how to improve the remission rate of treatment, improve patients' quality of life due to high tumor burden, increase disease control, and further bring better survival benefits is still a big challenge for third-line treatment. Regorafenib and TAS-102 have different mechanisms of action and different adverse reaction spectra. When the two drugs are used in combination, they may complement each other in terms of efficacy and are also less likely to have toxic effects.
In the RECOURSE study, 17% of patients in the TAS-102 treatment group had received prior treatment with regorafenib. Subgroup analysis showed that the efficacy of TAS-102 was not dependent on whether or not the patient had previously received regorafenib treatment. Therefore, the combination of regorafenib and TAS-102 may be a valuable treatment option for refractory mCRC. However, there is little clinical research data on whether the combination therapy could further improve efficacy and prolong patient survival compared to monotherapy. In 2021, a phase Ib small-sample study from Germany explored the combined use of regorafenib and TAS-102 in third-line treatment of mCRC. The study included 12 patients who received combined treatment with regorafenib and TAS-102 in third-line treatment. After a 3+3 dose-exploration trial, three cases of DLT were all grade 3 hypertension related to regorafenib. The combination of TAS-102 25 mg/m2 twice daily and regorafenib 120 mg was well tolerated, with a median PFS of 3.81 months (95% CI: 1.51-5.2), and a median OS of 11.1 months (95% CI: 2.3-18.2). The results of this early-phase clinical trial suggest that compared to regorafenib monotherapy in the CORRECT study with a median PFS of less than two months and a median OS of less than seven months, the third-line combination treatment of regorafenib and TAS-102 may potentially provide patients with greater clinical benefits. In conclusion, the combination therapy of regorafenib and TAS-102 may be further explored and studied for late-stage colorectal cancer in third-line or after third-line treatment.
The aim of this study is to evaluate the clinical benefits and safety of the combination of regorafenib and TAS-102 compared to regorafenib monotherapy in patients with advanced colorectal cancer who have failed second-line or later treatments. The efficacy and safety of the combination therapy will be fully evaluated, and explorations of efficacy, PFS, OS, safety, and related biomarkers associated with the combined treatment of regorafenib and TAS-102 will be conducted.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- controlled, randomized
| Arm | Type | Receives |
|---|---|---|
| A: Regorafenib+TAS-102 combination therapy | Experimental | Drug: Regorafenib, Drug: Trifluridine/TipiracilRegorafenib 80mg ,orally, once a day, d1-28, every 28 days, TAS-102，35mg/m2, orally，twice a day, d1-5 \& d15-19，every 28 days |
| B：Regorafenib monotherapy | Active comparator | Drug: RegorafenibRegorafenib, 120mg orally, once a day, d1-21, every 28 days (If the patient's body surface area is less than 1.5m2, the starting dose of regorafenib is 80mg) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Patients with histologically confirmed recurrent/metastatic colorectal adenocarcinoma.
- Patients who have failed at least one prior standard first- or second-line therapy, including fluoropyrimidine-based therapy, oxaliplatin, irinotecan, and bevacizumab. Treatment failure is defined as either radiographic evidence of disease progression or unacceptable toxicity during treatment or within three months following completion of therapy.
- (Note: a. each line of therapy should include at least one or more chemotherapy agents administered for at least one cycle; b. adjuvant/neoadjuvant therapy is allowed. If relapse or metastasis occurs during or within six months after completion of adjuvant/neoadjuvant therapy, it is considered a failure of first-line chemotherapy for progressive disease. c. For patients with RAS/RAF wild-type tumors, the use of an EGFR inhibitor is not required.)
- At least one measurable lesion, with the longest diameter ≥10 mm on spiral CT or ≥20 mm on conventional CT (RECIST 1.1 criteria).
- ECOG performance status of 0-2.
Key exclusion criteria (18 listed)
- Proteinuria ≥2+ on dipstick or 24-hour urinary protein ≥1.0 g/24 h.
- Abnormal coagulation function (PT>16s, APTT>43s, TT>21s, Fbg<2g/L), bleeding tendency, or receiving thrombolysis or anticoagulation therapy.
- Patients at risk of gastrointestinal bleeding, including those with active digestive ulcers and fecal occult blood (++) and those with histories of black stools or hematemesis within three months.
- Receiving systemic antitumor therapy, including chemotherapy, signal transduction inhibitors, or immune therapies, within three weeks prior to screening.
- Patients with uncontrolled hypertension (systolic blood pressure >140 mmHg, diastolic blood pressure >90 mmHg) despite antihypertensive medication, grade I or higher coronary heart disease, grade I or higher arrhythmia (including QTc interval prolongation with ≥450 ms for men and ≥470 ms for women), or grade I or higher heart failure.
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 |
|---|---|---|
| RegorafenibAlso: Stivagathis anti-angiogenesis targeting drug is one of the standard third-line treatment options for patients with metastatic colorectal cancer | Drug | A: Regorafenib+TAS-102 combination therapy, B：Regorafenib monotherapy |
| Trifluridine/TipiracilAlso: TAS-102this chemotherapeutic drug is also one of the standard third-line treatment options for patients with metastatic colorectal cancer | Drug | A: Regorafenib+TAS-102 combination therapy |
Primary outcome
PFS
Time frame: from the time signing of ICF until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
progression free survival
4 secondary outcomes
OS
Time frame: from the time signing of ICF until the date of death from any cause, assessed up to 36 months
ORR
Time frame: the rate of patients with CR and PR, through study completion, an average of 1 year
DCR
Time frame: the rate of patients with CR, PR and SD, through study completion, an average of 1 year
DOR
Time frame: the time between the first tumor evaluation for CR or PR and the first evaluation for PD(Progressive Disease) or death from any cause, assessed up to 36 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2023.
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CRC
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. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Regorafenib and Trifluridine/Tipiracil in people with Metastatic Colorectal Cancer, run by Fudan University 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 10 inclusion and 18 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: status not confirmed, as of the sponsor's last update on 1 Aug 2023. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PFS (time frame: from the time signing of ICF until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 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 1 Aug 2023.