Dual EGFR/HER2 Blockade Combined With Irinotecan for the Treatment of HER2-Positive Metastatic Colorectal Cancer

ConditionsHER2 Positive Colorectal Cancer (CRC)

Trial statusNot yet recruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age18-75

SponsorSun Yat-sen University

About this trial

In colorectal cancer (CRC), HER2 has emerged as a critically targeted biomarker in recent years. Although multiple clinical trials have demonstrated the potential of HER2-targeted therapies in HER2-positive (overexpressed/amplified) metastatic CRC (mCRC), the duration of treatment response remains short with rapid disease progression. This underscores the urgent need to develop novel therapeutic strategies for HER2-positive mCRC. The EGFR pathway is constitutively activated in CRC and mediates resistance to HER2-targeted therapies through the formation of EGFR-HER2 heterodimers. Notably, EGFR-targeting antibodies combined with irinotecan can reverse irinotecan chemoresistance. Building upon these mechanisms, this study proposes to evaluate the combination of trastuzumab (anti-HER2), cetuximab beta (anti-EGFR), and irinotecan in chemotherapy-refractory HER2-positive mCRC.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Signed and dated informed consent must be obtained voluntarily from the subject prior to performing any study-related procedures (non-routine care), in accordance with regulatory and institutional guidelines.

18 to 75 years of age, inclusive.

Histologically or cytologically confirmed adenocarcinoma of the colon or rectum with evidence of distant metastasis.

Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Disqualifiers

Known KRAS, NRAS, or BRAF mutations detected by ctDNA testing prior to enrollment; or tumors with mismatch repair deficiency (dMMR) or high microsatellite instability (MSI-H).

Concurrent intestinal obstruction, active bleeding, or perforation requiring emergency surgery.

Major surgery (e.g., laparotomy, thoracotomy, or organ resection via laparoscopy) or significant trauma within 4 weeks prior to study entry (surgical incision must be fully healed before enrollment).

Active coronary artery disease within 12 months before screening, including severe/unstable angina, newly diagnosed angina, or myocardial infarction.

Trial design

Design model

Single group

Treatments tested in this trial

Trastuzumab +Cetuximab β+Irinotecan
Drug
Trastuzumab 4 mg/kg , Cetuximab β: 500 mg/m² ,Irinotecan 180 mg/m², repeat once every 2 weeks

Treatment groups

34 Participants

are divided into 1 treatment group

Group A: Trastuzumab +Cetuximab β+IrinotecanExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

6-month progression-free-survival rates

Progression-free survival defined as the time from randomization to documented disease progression according to RECIST or death from any cause. We computed the 6-month PFS rate based on the available follow-up data.

Time frame

2 years

Secondary outcomes

Objective response rate

defined as the percentage of patients with complete or partial response according to RECIST

Time frame

2 years

Disease control rate

defined as the percentage of patients with CR + PR + SD according to RECIST

Time frame

2 years

overall survival

defined as the time from randomization to death from any cause

Time frame

3 years

Incidence of participants with treatment-related adverse events as assessed by CTCAE v5.0

Percentage of patients, experiencing a specific adverse event, according to National Cancer Institute Common Toxicity Criteria (version 5.0), during the induction and the maintenance phases of treatment.

Time frame

3 years

Other outcomes

Treatment-emergent genetic variants analysis by ctDNA sequencing

Longitudinal assessment of somatic mutation profiles in circulating tumor DNA (ctDNA) using next-generation sequencing (NGS) to correlate genetic variants (e.g., HER2/EGFR/RAS pathway alterations) with objective response rate (ORR) per RECIST 1.1 criteria.

Time frame

2 years

Baseline proteomic predictive biomarkers for treatment efficacy

Quantitative proteomic profiling of baseline plasma and tissue samples to identify predictive biomarkers correlated with therapeutic response.

Time frame

3 years

Treatment-induced proteomic alterations

Quantitative proteomic analysis of plasma and tissue samples to detect therapy-mediated changes in protein expression and phosphorylation patterns.

Time frame

3 years

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Sun Yat-sen University

Lead sponsor

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: