A Real-World Study of Neoadjuvant/Conversion Therapy for Colorectal Cancer With Chemotherapy And Anti-Angiogenic Targeted Agents

Official title

A Real-World Study of Neoadjuvant/Conversion Therapy for Locally Advanced or Metastatic Colorectal Cancer With Chemotherapy Combined With Anti-Angiogenic Targeted Agents

Overview

Fruquintinib is already the standard third-line treatment for metastatic colorectal cancer, but the efficacy of fruquintinib in neoadjuvant and conversion therapy for locally advanced/advanced colorectal cancer has not yet been reported. This study aims to observe the efficacy and safety of fruquintinib combined with chemotherapy in neoadjuvant or conversion therapy for colorectal cancer patients in the real world.

Interventions

• Combination product corhot1: chemotherapy combined with fruquintinib
  Chemotherapy Drugs: Selection based on clinical guidelines/indications and patient condition.For example, recommended chemotherapy regimens: mFOLFOX6 or CAPEOX. Fruquintinib: 3mg (starting dose), PO (once daily). Dosing schedule and dosage can be adjusted based on concurrent chemotherapy and immune checkpoint inhibitors. Have received fruquintinib treatment for at least 2 cycles.
• Combination product corhot2: chemotherapy combined with fruquintinib
  Chemotherapy Drugs: Selection based on clinical guidelines/indications and patient condition.For example, recommended chemotherapy regimens: mFOLFOX6 or CAPEOX. Fruquintinib: 3mg (starting dose), PO (once daily). Dosing schedule and dosage can be adjusted based on concurrent chemotherapy and immune checkpoint inhibitors. Have received fruquintinib treatment for at least 2 cycles.

Primary outcome measures

• Corhot1: Pathological Complete Response Rate (pCR) [Time frame: Time from the first treatment up to 12 weeks]
• Corhot2: R0 surgical conversion rate [Time frame: Time from the first treatment up to 24 weeks]

Secondary outcome measures (10)

• Corhot1: R0 resection rate [Time frame: Time from the first treatment up to 12 weeks]
• Corhot1: Event-Free Survival (EFS) [Time frame: Time from the first treatment up to 2 years]
• Corhot1: 1-year Event-Free Survival (EFS) rate [Time frame: Time from the first treatment up to 12 months.]
• Corhot1 and Corhot2: Overall Survival (OS) [Time frame: Time from the first treatment up to 2 years.]
• Corhot1 and Corhot2: 1-year Overall Survival (OS) rate [Time frame: Time from the first treatment up to 12 months.]
• Corhot1 and Corhot2: Objective Response Rate (ORR) [Time frame: corhot1 ：Time from the first treatment up to 12 weeks. Corhot2：Time from the first treatment up to 2 years.]
• Corhot1 and Corhot2: Disease Control Rate (DCR) [Time frame: corhot1 ：Time from the first treatment up to 12 weeks. Corhot2：Time from the first treatment up to 2 years.]
• Corhot2: Curative Surgery Conversion Rate [Time frame: Time from the first treatment up to 24 weeks]
• Corhot2: Progression-Free Survival (PFS) [Time frame: Time from the first treatment up to 2 years.]
• Corhot1and Corhot2: Adverse events [Time frame: through study completion, an average of 1 year]

Eligibility criteria

Inclusion criteria

• Patients must meet all of the following criteria to be enrolled in this study:

• Age ≥18 years and ≤75 years;
• Either gender;
• Patients with histologically confirmed colorectal cancer. For the neoadjuvant treatment cohort: Rectal cancer is limited to high rectal cancer, but patients with mid to low rectal cancer who are unwilling or unsuitable for neoadjuvant chemoradiotherapy can also be included.
• Neoadjuvant treatment cohort: Clinically staged as stage II (T3-4N0M0) or stage III (T1-4N1-2M0) and initially resectable; patients with clinical stage M1 but initially resectable can also be included in the neoadjuvant treatment cohort, such as patients with stage IV liver oligometastasis. Conversion treatment cohort: Patients with initially unresectable but potentially resectable locally advanced or advanced distant metastatic colorectal cancer (according to AJCC 8th), and patients with locally advanced low rectal cancer who are unsuitable or unwilling to undergo chemoradiotherapy can also be included.
• Have received chemotherapy and fruquintinib for at least 2 cycles. For the neoadjuvant therapy cohort, patients who have not previously received anticancer treatment (radiotherapy, chemotherapy, targeted therapy, or immunotherapy, etc.). The patients are eligible for inclusion in the analysis set if they have received fruquintinib treatment for at least 2 cycles and have undergone at least one tumor assessment after baseline. All patients included in the efficacy analysis are included in the safety analysis set.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 before treatment.
• Expected survival time of >6 months before neoadjuvant therapy and >3 months before conversion therapy.
• No significant organ dysfunction or drug contraindications before receiving neoadjuvant or conversion therapy.
• There is no mandatory requirement for target lesions. Objective response rate (ORR) assessment is based on all evaluable patients, regardless of the presence of target lesions. For patients without target lesions, those assessed as non PR/non PD will be analyzed as stable disease (SD).

Exclusion criteria

• Patients meeting any of the following criteria are not eligible to enter the study:

• History of other primary malignant tumors, except: (1) complete remission of malignant tumors at least 2 years before enrollment and no need for other treatment during the study period; (2) adequately treated non-melanoma skin cancer or malignant melanoma without evidence of disease recurrence; (3) adequately treated in situ carcinoma.
• dMMR/MSI-H.
• Female patients who are pregnant or lactating.
• Known allergy (Grade 3 or higher allergic reaction) or contraindication to anti-angiogenic drugs or chemotherapy drug components.
• Use of non-study drug treatments during the study period that may interfere with the analysis.
• Patients who did not undergo any tumor efficacy assessment after receiving neoadjuvant or conversion therapy.
• Less than 2 cycles of fruquintinib neoadjuvant or conversion therapy.
• Patients with insufficient follow-up information as judged by the investigator (such as not returning to the hospital for treatment or efficacy assessment after initial treatment).

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

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

China · 1 center

• Zhongnan Hospital of Wuhan University — Wuhan

Identifiers

NCT: NCT06470178 · HMPL-013-C2-CRC09

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗