Surufatinib, Toripalimab and Chemotherapy in Second-line MT and MSS CRC

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

To determine the efficacy and safety of surufatinib, toripalimab and chemotherapy in second-line RAS/BRAF mutant and MSS colorectal cancer

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: Surufatinib; Drug: Toripalimab; Drug: chemotherapy

• Study Type: Interventional
• Enrollment (Estimated): 61
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Weijia Fang, MD.; Phone Number: +86-571-87235147; Email: weijiafang@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310006
      • Recruiting
      • First affiliated hospital, Zhejiang University
      • Principal Investigator: Weijia fang, MD
      • Contact: Weijia Fang, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Surufatinib, Toripalimab and Chemotherapy; Second line CRC patients received surufatinib 250mg po qd , toripalimab 3mg/kg ivgtt q2w and chemotherapy according to the first line treatment, until disease progression or intolerable toxicity	Drug: Surufatinib; 250mg per oral, once daily; Drug: Toripalimab; 3mg/kg IV, once every 2 weeks; Drug: chemotherapy; oxaliplatin or irinotecan based regimens, according to the first line treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate	the proportion of patients in a trial whose tumor is destroyed or significantly reduced by a drug. ORR is generally defined as the sum of complete responses (CRs) - patients with no detectable evidence of a tumor over a specified time period - and partial responses (PRs) - patients with a decrease in tumor size over a specified time period.	2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Refers to the time of death from enrollment to any cause	2 years
Progression Free Survival	the time elapsed between treatment initiation and tumor progression	6 months

Collaborators and Investigators

• Sponsor: Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2021
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: November 28, 2020
• First Submitted That Met QC Criteria: November 28, 2020
• First Posted (Actual): December 4, 2020

Study Record Updates

• Last Update Posted (Actual): July 17, 2023
• Last Update Submitted That Met QC Criteria: July 14, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: APHRODITE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No