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

NCT05963490 | Recruiting Phase 2

• 1 other identifier: FDRT-2023-118-3237
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

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.

Conditions

Microsatellite Stable Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• OS

  Defined as the time from initiation of treatment to death from any cause.

  Up to 2 years

Secondary Outcomes (5)

• PFS

  Up to 2 years

• DCR

  Up to 1 year

• ORR

  Up to 1 year

• DoR

  Up to 1 year

• Adverse events

  Up to 1 year

Study Arms (2)

monotherapy

ACTIVE COMPARATOR

a total of 54 patients will receive regorafenib monotherapy.

Drug: Regorafenib

combination therapies

EXPERIMENTAL

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.

Drug: Toripalimab; Radiation: Radiotherapy; Drug: Regorafenib

Interventions

Regorafenib DRUG

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

Also known as: Stivarga

monotherapy

Toripalimab DRUG

240 mg intravenously every 3 weeks

combination therapies

Radiotherapy RADIATION

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

combination therapies

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years old
• An Eastern Cooperative Oncology Group (ECOG) performance status ≤1
• Life expectancy of at least 3 months
• Histopathological confirmed MSS/pMMR adenocarcinoma of the colon or rectum
• At least one evaluable metastatic lesion for radiotherapy according to RECIST 1.1
• Progressed on or after the standard first-and second-line therapies or stopped standard therapy because of unacceptable toxic effects
• Previous radiotherapy completed at least 4 weeks before randomization
• 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
• Sign the informed consent and have good compliance

You may not qualify if:

• History of previous treatment with regorafenib and ICIs such as anti-PD-1 or anti-PD-L1 mAbs
• Current severe cardiovascular diseases such as unstable angina, congestive heart failure, or serious cardiac arrhythmia requiring medication
• Acute cardiac infarction or cerebral ischemic stroke occurred within 6 months before recruitment
• Active autoimmune diseases and immunodeficiencies, known history of organ transplantation, or systematic use of immunosuppressive agents
• 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
• Positive human immunodeficiency virus (HIV) infection, active syphilis infection, or active pulmonary tuberculosis infection
• Severe infections requiring systemic antibiotics, antifungal or antiviral therapy
• Uncontrollable pleural effusion, pericardial effusion, or ascites
• 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.
• Known history of severe neurological or mental illness such as schizophrenia, dementia, or epilepsy
• Known history of allergy to any component involved in this study.
• Pregnancy or breast-feeding women

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, China

RECRUITING

Related Publications (1)

• 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.

  PMID: 37869085 DERIVED

MeSH Terms

Interventions

regorafenib; toripalimab; Radiotherapy

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Zhen Zhang, MD, PHD

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhen Zhang, MD, PHD

CONTACT

18801735029; zhen_zhang@fudan.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 19, 2023
• First Posted: July 27, 2023
• Study Start: April 25, 2023
• Primary Completion: April 25, 2025
• Study Completion: April 25, 2026
• Last Updated: September 24, 2024

Record last verified: 2024-09

Locations

CN (1)