Combining regorafenib and TAS-102 for advanced colorectal cancer treatment

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

This study is testing if combining two cancer drugs, regorafenib and TAS-102, can help people with advanced colorectal cancer live longer and feel better compared to using regorafenib alone.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 101 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Fudan University (Academic / other)
• Drugs / interventions: bevacizumab, apatinib, fruquintinib, anlotinib, lenvatinib, chemotherapy, radiation
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT05970705 on ClinicalTrials.gov

What this trial studies

This study evaluates the effectiveness of combining regorafenib with TAS-102 compared to regorafenib alone in patients with metastatic colorectal cancer who have already undergone at least two lines of treatment. The aim is to determine if this combination can improve survival and safety outcomes for patients facing limited options. By leveraging the different mechanisms of action of both drugs, the study seeks to enhance treatment efficacy and reduce adverse effects. A total of 101 patients will be randomly assigned to receive either the combination therapy or monotherapy in a 1:1 ratio.

Who should consider this trial

Good fit: Ideal candidates are patients with histologically confirmed metastatic colorectal adenocarcinoma who have failed at least one prior standard therapy.

Not a fit: Patients who have not received prior treatment or those with contraindications to either regorafenib or TAS-102 may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a more effective treatment option for patients with advanced colorectal cancer who have limited therapeutic alternatives.

How similar studies have performed: While previous studies have shown limited efficacy for regorafenib and TAS-102 as monotherapies, this combination approach is novel and has not been extensively tested.

Eligibility criteria

A total of 101 patients with metastatic colorectal cancer who meet the inclusion criteria and do not meet the exclusion criteria for receiving third-line or later-line therapy will be randomly assigned to receive corresponding treatment in a 1:1 ratio.

Inclusion Criteria:

The subjects must meet all of the following criteria to be eligible for this study:

1. Patients with histologically confirmed recurrent/metastatic colorectal adenocarcinoma.
2. 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.)
3. At least one measurable lesion, with the longest diameter ≥10 mm on spiral CT or ≥20 mm on conventional CT (RECIST 1.1 criteria).
4. ECOG performance status of 0-2.
5. Life expectancy of ≥12 weeks.
6. 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.
7. Women of childbearing potential must use effective contraception.
8. 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.

Exclusion Criteria:

Patients who meet any of the following criteria will be excluded from the study:

1. Proteinuria ≥2+ on dipstick or 24-hour urinary protein ≥1.0 g/24 h.
2. Abnormal coagulation function (PT\>16s, APTT\>43s, TT\>21s, Fbg\<2g/L), bleeding tendency, or receiving thrombolysis or anticoagulation therapy.
3. 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.
4. Receiving systemic antitumor therapy, including chemotherapy, signal transduction inhibitors, or immune therapies, within three weeks prior to screening.
5. 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.
6. Patients with a history of thrombotic or embolic events requiring treatment within the preceding six months.
7. Patients who have received radiation therapy targeting the selected target lesion.
8. Symptomatic brain or meningeal metastasis.
9. Uncontrolled pleural or peritoneal effusion.
10. Receiving kidney dialysis.
11. Serious or uncontrolled infection.
12. Pregnant or lactating women or women of childbearing potential without adequate contraception.
13. Multiple factors affecting oral drug administration (dysphagia, chronic diarrhea, and bowel obstruction).
14. Patients who have been treated with small molecule tyrosine kinase inhibitors containing VEGFR (such as apatinib, fruquintinib, anlotinib, and lenvatinib).
15. Patients who have been treated with TAS-102.
16. Participation in another clinical study within four weeks prior to screening.
17. Patients with comorbidities that could seriously endanger patients' safety or affect their completion of the study.

Where this trial is running

Shanghai, Shanghai Municipality

• Fudan University Shanghai Cancer Center — Shanghai, Shanghai Municipality, China (Recruiting)

Conditions Metastatic Colorectal Cancer; metastatic colorectal cancer; regorafenib; TAS-102; Trifluridine/Tipiracil