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

Phase 2

Recruiting

• Conditions: Microsatellite Stable Metastatic Colorectal Cancer
• Interventions: Drug: Regorafenib; Drug: Toripalimab; Radiation: Radiotherapy

• Registration Number: NCT05963490
• Lead Sponsor: Fudan University

Brief Summary

The study compares the efficacy and safety of regorafenib alone or in combination with stereotactic ablative radiotherapy (SABR) 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 45 patients will receive regorafenib monotherapy. Experimental arm: a total of 45 patients will first receive 1 cycle of regorafenib and toripalimab followed by SABR/LDRT radiotherapy. Regorafenib and toripalimab will be continued after the completion of radiotherapy. The objective response rate (ORR), survival benefits, 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 4-8 fractions of 8-12Gy via SABR and up to 1-10Gy at 0.5-2Gy/fraction via LDRT.

Study Timeline

• Study Start: 2023-04-25
• Status Verified: 2023-07
• Study First Submitted: 2023-07-19
• Study First Submitted QC: 2023-07-19
• Last Update Submitted: 2023-07-19
• Study First Posted: 2023-07-27
• Last Update Posted: 2023-07-27
• Primary Completion: 2024-04-25
• Study Completion: 2026-04-25

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 90

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 two evaluable metastatic lesions for SABR and LDRT 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
monotherapy	Regorafenib	a total of 54 patients will receive regorafenib monotherapy.
combination therapies	Radiotherapy	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.
combination therapies	Regorafenib	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.
combination therapies	Toripalimab	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.

Primary Outcome Measures

Name	Time	Method
OS	Up to 2 years	Defined as the time from initiation of treatment to death from any cause.

Secondary Outcome Measures

Name	Time	Method
PFS	Up to 2 years	Defined as the time from initiation of treatment to PD or death from any cause.
DCR	Up to 1 year	The percentage of patients with disease control in all metastatic lesions. Disease control is defined as CR, PR, or stable disease (SD) per RECIST v1.1 and iRECIST after treatment.
ORR	Up to 1 year	The percentage of patients with objective response in all metastatic lesions.
DoR	Up to 1 year	Defined as the time between PR/CR and subsequent progression disease (PD) per RECIST v1.1 and iRECIST or death from any cause.
Adverse events	Up to 1 year	The percentage of patients with treatment-related acute toxicities as assessed by NCI CTCAE v5.0, from treatment initiation until 90 days upon completion of immunotherapy.

Trial Locations

Locations (1)

Fudan University Shanghai Cancer Center; 🇨🇳 Shanghai, China