Combination treatment for second-line colorectal cancer

Surufatinib and Toripalimab Combined With Chemotherapy for Second-line Treatment of Advanced RAS/BRAF Mutant and Microsatellite Stable Colorectal Cancer

This study is testing a new combination of treatments for adults with advanced colorectal cancer that hasn’t improved with previous therapy, to see if it helps them live longer and feel better.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 61 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Zhejiang University (Academic / other)
• Drugs / interventions: immunotherapy, radiation, toripalimab, surufatinib, chemotherapy
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT04653480 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the efficacy and safety of a combination of surufatinib, toripalimab, and chemotherapy in patients with second-line RAS/BRAF mutant and microsatellite stable colorectal cancer. The study aims to enroll patients who have experienced progression on first-line therapy and are between the ages of 18 and 75. Participants will receive the combination treatment to assess its impact on their overall survival and disease progression. The trial is conducted at the First Affiliated Hospital of Zhejiang University in Hangzhou, Zhejiang.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with RAS/BRAF mutant and microsatellite stable colorectal cancer who have progressed on first-line therapy.

Not a fit: Patients who have received prior immunotherapy or those with significant comorbidities may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with advanced colorectal cancer who have limited treatment choices.

How similar studies have performed: Other studies have shown promise with similar combination therapies in colorectal cancer, suggesting potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Age ≥ 18 years, ≤75 years
2. Histologically confirmed colorectal cancer with distant metastasis.
3. ECOG 0-1
4. Progression on first line therapy
5. RAS/BRAF mutant and microsatellite stable
6. Patients can swallow pills normally
7. Expected overall survival ≥6 months
8. Blood routine: no blood transfusion or blood products usage within 14 days, G-CSF or other hematopoietic stimulator was not used. WBC counts \> 3000/µl，Absolute neutrophil count (ANC) ≥ 1500 cells/µl，Platelet count ≥ 100,000/µl，Hemoglobin ≥ 9.0 g/dL.
9. AST, ALT and alkaline phosphatase ≤ 2.5 times the upper limit of normal (ULN)，Serum bilirubin ≤ 1.5 x ULN，creatinine\<ULN
10. Prothrombin time (PT), international standard ratio (INR) ≤1.5 × ULN
11. Patients who have not received immunotherapy
12. Women of childbearing age must be willing to use adequate contraceptives during the study period of drug treatment;
13. Informed consent has been signed.

Exclusion Criteria:

1. Patients have received ≥2 line systemic therapy;
2. Active bleeding within 3 months; Occurrence of arterial/venous thrombosis within 6 months; Hereditary or acquired bleeding (e.g., clotting dysfunction) or thrombotic tendencies; Full dose oral or injectable anticoagulants or thrombolytic drugs for therapeutic purposes are currently being used or have been used recently (10 days prior to the commencement of study treatment); Surgery (except for biopsy) was performed within 4 weeks prior to the study or the surgical incision was not fully healed; Aspirin (\> 325 mg/ day) or dipyridamole, ticlopidine, clopidogrel, and silotazole are currently being used or have recently been used (10 days prior to the study).
3. Systemic corticosteroids or other systemic immunosuppressive drugs were used within 2 weeks prior to treatment. Immunosuppressive drugs were started or expected to be used during the trial. Inhaled corticosteroids, physiologic replacement doses of glucocorticoids are allowed.
4. Certain or suspected brain metastases.
5. The patient has a history of autoimmune disease.
6. Serious uncontrolled systemic diseases, such as severe active infections;
7. A person is known to be infected with the immunodeficiency virus (HIV) or known to be HIV-positive;
8. Patients have suffered from other malignancies in the past 5 years except cervical carcinoma in situ or basal cell carcinoma of the skin
9. Untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers (HBV DNA \>500 IU/mL) or active HCV carriers with HCV RNA can be detected. Remarks: Inactive hepatitis B surface antigen (HBsAg) carriers, treated and stable hepatitis B patients (HBV DNA \< 500 IU/mL) may be enrolled
10. Anti-infective therapy was not discontinued 14 days before the study;
11. A prior history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonia, and symptomatic interstitial lung disease or the presence of active pneumonia on a chest CT scan within 4 weeks prior to the study.
12. Patients have a history of intestinal obstruction within six months. Patients with incomplete obstruction syndrome of ileus at the time of initial diagnosis may be enrolled in the study if they have received definitive (surgical) treatment to resolve the symptoms, as assessed by the investigator.
13. Patients Have high blood pressure that cannot be well controlled by antihypertensive medication (systolic ≥140 mmHg or diastolic ≥90 mmHg)
14. Urine routine indicated urinary protein ≥++ and confirmed 24-hour urinary protein \>1.0g;
15. Known to be allergic to any study drug;
16. Patients have participated in other drug clinical studies within 4 weeks before enrollment;
17. Lactating women
18. According to the judgment of the researcher, the patient may have other factors that may affect the results of the study or cause the study to be terminated, such as alcohol abuse, drug abuse, other serious diseases (including mental diseases) requiring combined treatment. Patients have severe laboratory abnormalities, which will affect the safety of the patient.

Where this trial is running

Hangzhou, Zhejiang

• First affiliated hospital, Zhejiang University — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Study coordinator: Weijia Fang, MD.

Conditions Colorectal Cancer