A Phase Ⅱ/Ⅲ Clinical Trial of RC148 Plus Chemotherapy as 1L Therapy for Unresectable or Metastatic Colorectal Cancer

Official title

A Randomized, Multicenter, Phase Ⅱ/Ⅲ Study of RC148 Combined With Chemotherapy Versus Bevacizumab Combined With Chemotherapy as First-line Treatment for Unresectable or Metastatic Colorectal Cancer

Overview

This is a Phase Ⅱ/Ⅲ study. The purpose of this study is to evaluate the efficacy and safety of RC148 combined with chemotherapy for the first-line treatment of unresectable metastatic colorectal cancer (CRC)

Detailed description

Primary objective in Phase II: To preliminarily evaluate the efficacy of RC148 combined with chemotherapy as first - line treatment for unresectable or metastatic CRC.

Primary objective in Phase III: To evaluate the efficacy of RC148 combined with chemotherapy compared with bevacizumab combined with chemotherapy as first - line treatment for unresectable or metastatic CRC.

Interventions

• Drug RC148 (Dose 1) plus Capecitabine and Oxaliplatin
  RC148 (Dose 1) plus Capecitabine and Oxaliplatin
• Drug RC148 (Dose 2) plus Capecitabine and Oxaliplatin
  RC148 (Dose 2) plus Capecitabine and Oxaliplatin

Primary outcome measures

• Objective Response Rate (ORR) [Time frame: 24 months]

Secondary outcome measures (5)

• Duration of Response (DoR) [Time frame: 24 months]
• Disease Control Rate (DCR) [Time frame: 24 months]
• Time to Response (TTR) [Time frame: 24 months]
• Overall Survival (OS) [Time frame: 36 months]
• AEs/SAE [Time frame: 36 months]

Eligibility criteria

Inclusion criteria

• Voluntarily agree to participate in the study, sign the informed consent form, and be able to comply with the study protocol.
• Aged 18-75 years old (including 18 years old and 75 years old).
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• Expected survival period ≥ 12 weeks.
• At least one measurable lesion according to RECIST v1.1 criteria.
• Histologically or cytologically confirmed colorectal adenocarcinoma, judged by the investigator as unsuitable for curative treatment, and no prior systemic anti-tumor treatment in the recurrent or metastatic stage.
• Subjects must be able to provide tumor tissue samples for biomarker detection.
• Adequate bone marrow, liver, kidney, and coagulation function.
• Female subjects of childbearing potential must agree to use at least one medically approved contraceptive method during the study treatment and for 6 months after the end of the study treatment, and must have a negative blood pregnancy test within 7 days before study enrollment; male subjects must agree to use at least one medically approved contraceptive method during the study treatment and for 6 months after the end of the study treatment.

Exclusion criteria

• Known to have microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR).
• Imaging shows obvious tumor necrosis or cavitation, and the investigator judges that participation in the study may increase the risk of bleeding.
• Subjects with brain metastases.
• Toxicities from prior anti-tumor therapy have not recovered to ≤ grade 1 according to NCI-CTCAE v6.0.
• Known hypersensitivity or delayed-type allergy to any component of the study drug or similar drugs.
• Subjects with refractory nausea and vomiting, chronic gastrointestinal diseases, or other diseases that may interfere the adequate absorption, distribution, metabolism, or excretion of oral drugs.
• Subjects with acute, chronic, or symptomatic infections.
• Subjects with diagnosed or suspected interstitial lung disease (ILD), drug-related pneumonia, radiation pneumonitis, severe impairment of lung function, or other lung diseases.
• Subjects with active inflammatory bowel disease, a history of gastrointestinal perforation and/or fistula, or clinical symptoms of gastrointestinal obstruction.
• Subjects with severe arterial/venous thromboembolic events within 6 months before randomization.
• Active gastrointestinal bleeding, hemoptysis, peptic ulcer, or hemorrhagic events requiring intervention within 28 days before randomization; or presence of severe esophagogastric varices or epistaxis.
• Presence of symptomatic or intervention-requiring third-space effusions.
• Subjects with active or previously diagnosed autoimmune diseases that may recur.
• History of other invasive malignant tumors within 5 years before randomization, or presence of any residual evidence of previously diagnosed malignant tumors.
• Subjects who are pregnant, lactating, or planning to become pregnant.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 19 centers

• Beijing Cancer Hospital — Beijing
• Beijing Friendship Hospital, Capital Medical University — Beijing
• Chongqing University Cancer Hospital — Chongqing
• Fujian Medical University Union Hospital — Fuzhou
• Meizhou People's Hospital — Meizhou
• Guangxi Medical University Cancer Hospital — Nanjing
• The Fourth Hospital of Hebei Medical University and Hebei Tumor Hospital — Shijiazhuang
• The First Affiliated Hospital of Zhengzhou University — Zhengzhou
• … and 11 more centers

Identifiers

NCT: NCT07462143 · RC148-C303

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗