Regorafenib Alone or in Combination With Hypofractionated/Low-dose Radiotherapy Plus Toripalimab for Metastatic Colorectal Cancer

NCT ID: NCT05963490

Last Updated: 2024-09-24

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 108 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-04-25
• Study Completion Date: 2026-04-25

Brief Summary

The study compares the efficacy and safety of regorafenib alone or in combination with hypofractionated radiotherapy and low-dose radiotherapy (LDRT) plus toripalimab in patients with microsatellite stable metastatic colorectal cancer (MSS mCRC). Patients are randomly assigned (1:1) into the control arm and the experimental arm. Control arm: a total of 54 patients will receive regorafenib monotherapy. Experimental arm: a total of 54 patients will first receive 1 cycle of regorafenib and toripalimab followed by hypofractionated/low-dose radiotherapy. Regorafenib and toripalimab will be continued after the completion of radiotherapy. The survival benefits, response rates, and adverse effects will be analyzed.

Detailed Description

Control arm: regorafenib 120 mg orally once daily on days 1-21 of each 28 days cycle.

Experimental arm: regorafenib is administered 80 mg once daily on days 1-21 of each 28 days cycle with intravenous toripalimab 240 mg every 3 weeks. Radiotherapy regimes include hypofractionated radiotherapy (5 fractions of 4-12Gy) and low-dose radiotherapy (5 fractions of 0.5-2Gy).

Conditions

Microsatellite Stable Metastatic Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

monotherapy

a total of 54 patients will receive regorafenib monotherapy.

Group Type: ACTIVE_COMPARATOR

Regorafenib

Intervention Type: DRUG

Regorafenib 120 mg orally once daily on days 1-21 of each 28 days cycle.

combination therapies

a total of 54 patients will first receive 1 cycle of regorafenib and toripalimab followed by hypofractionated/low-dose radiotherapy. Regorafenib and toripalimab will be continued after the completion of radiotherapy.

Group Type: EXPERIMENTAL

Toripalimab

Intervention Type: DRUG

240 mg intravenously every 3 weeks

Radiotherapy

Intervention Type: RADIATION

hypofractionated radiotherapy (5 fractions of 4-12Gy) and low-dose radiotherapy (5 fractions of 0.5-2Gy).

Regorafenib

Intervention Type: DRUG

Regorafenib 80mg orally once daily on days 1-21 of each 28 days cycle.

Interventions

Regorafenib

Regorafenib 120 mg orally once daily on days 1-21 of each 28 days cycle.

Intervention Type: DRUG

Toripalimab

240 mg intravenously every 3 weeks

Intervention Type: DRUG

Radiotherapy

hypofractionated radiotherapy (5 fractions of 4-12Gy) and low-dose radiotherapy (5 fractions of 0.5-2Gy).

Intervention Type: RADIATION

Regorafenib

Regorafenib 80mg orally once daily on days 1-21 of each 28 days cycle.

Intervention Type: DRUG

Other Intervention Names

Stivarga

Eligibility Criteria

Inclusion Criteria

1. Age ≥18 years old

2. An Eastern Cooperative Oncology Group (ECOG) performance status ≤1

3. Life expectancy of at least 3 months

4. Histopathological confirmed MSS/pMMR adenocarcinoma of the colon or rectum

5. At least one evaluable metastatic lesion for radiotherapy according to RECIST 1.1

6. Progressed on or after the standard first-and second-line therapies or stopped standard therapy because of unacceptable toxic effects

7. Previous radiotherapy completed at least 4 weeks before randomization

8. Adequate bone-marrow, hepatic, and renal function: neutrophils ≥ 1.5 × 10^9/L, Hb ≥ 90 g/L, PLT ≥ 100 × 10^9/L, ALT/ AST≤2.5 ULN, Cr≤1 ULN

9. Sign the informed consent and have good compliance

Exclusion Criteria

1. History of previous treatment with regorafenib and ICIs such as anti-PD-1 or anti-PD-L1 mAbs

2. Current severe cardiovascular diseases such as unstable angina, congestive heart failure, or serious cardiac arrhythmia requiring medication

3. Acute cardiac infarction or cerebral ischemic stroke occurred within 6 months before recruitment

4. Active autoimmune diseases and immunodeficiencies, known history of organ transplantation, or systematic use of immunosuppressive agents

5. Active Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection: HBsAg positive or HBV DNA positive, anti-HCV antibody testing positive and confirmatory HCV RNA positive

6. Positive human immunodeficiency virus (HIV) infection, active syphilis infection, or active pulmonary tuberculosis infection

7. Severe infections requiring systemic antibiotics, antifungal or antiviral therapy

8. Uncontrollable pleural effusion, pericardial effusion, or ascites

9. Other malignancies within 5 years before recruitment, except for non-melanoma skin cancer, superficial bladder cancer, cervical carcinoma in situ, or breast cancer in situ that had been effectively treated.

10. Known history of severe neurological or mental illness such as schizophrenia, dementia, or epilepsy

11. Known history of allergy to any component involved in this study.

12. Pregnancy or breast-feeding women

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fudan University

OTHER

Sponsor Role: lead

Responsible Party

Zhen Zhang

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Zhen Zhang, MD, PHD

Role: PRINCIPAL_INVESTIGATOR

Fudan University

Locations

Fudan University Shanghai Cancer Center

Shanghai, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Zhen Zhang, MD, PHD

Role: CONTACT

zhen_zhang@fudan.edu.cn

18801735029

Facility Contacts

Zhen Zhang, MD, PHD

Role: primary

zhen_zhang@fudan.edu.cn

18801735029

References

Zhou S, Wang C, Shen L, Wang Y, Zhang H, Wu R, Wang Y, Chen Y, Xuan Y, Xia F, Zhang Z, Wan J. Regorafenib alone or in combination with high/low-dose radiotherapy plus toripalimab as third-line treatment in patients with metastatic colorectal cancer: protocol for a prospective, randomized, controlled phase II clinical trial (SLOT). Front Oncol. 2023 Oct 5;13:1274487. doi: 10.3389/fonc.2023.1274487. eCollection 2023.

Reference Type: DERIVED

PMID: 37869085 (View on PubMed)

Other Identifiers

FDRT-2023-118-3237

Identifier Type: -

Identifier Source: org_study_id