Optimization of Individualized Therapy for CRCs With Secondary RESISTance Towards Anti-EGFR Targeted Therapy Using an Avatar Model

Recruiting

• Conditions: UICC III; UICC II + RF; UICC IV Curative Intent; Colo-rectal Cancer; RAS Wild-type
• Interventions: Drug: targeted substance according to the avatar model

• Registration Number: NCT03263663
• Lead Sponsor: PD Dr. med. Volker Heinemann

Brief Summary

In this exploratory phase II trial, the possibility of a personalized treatment after resistance to cetuximab will be evaluated. Therefore, tumor material of all patients shall be obtained, transferred into avatars and treated the same way as in the patient until resistance arises. These resistant tumor cells are subsequently treated by different targeted treatment combinations in the mouse avatar model to find the most active drug or combination of drugs. This drug or combination of drugs may then be offered to the patient after cetuximab resistance has occurred. Multiple liquid biopsies shall be obtained in patients during first-line treatment with cetuximab as well as during second line experimental treatment to monitor mutations that may be associated with cetuximab resistance. Furthermore at the time of resistance a biopsy should be taken and analyzed to ensure that the mechanism of resistance seen in the avatar model matches with the mechanism of resistance in the individual patient.

Detailed Description

Not available

Study Timeline

• Study Start: 2017-01-01
• Status Verified: 2017-08
• Study First Submitted: 2017-08-24
• Study First Submitted QC: 2017-08-24
• Last Update Submitted: 2017-08-24
• Study First Posted: 2017-08-28
• Last Update Posted: 2017-08-28
• Primary Completion: 2021-01-01
• Study Completion: 2025-01-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1000

Inclusion Criteria

• Male and female patients age ≥ 18 years
• Written declaration of consent
• ECOG Performance Status 0-1
• Life expectancy> 3 months
• Histologically confirmed adenocarcinoma of the colon or rectum at stage UICC III or UICC IV
• Histologically confirmed adenocarcinoma of the colon or rectum in stage UICC II with one of the following risk factors: CEA> 200; T4 tumor, emergency surgery, <12 distant lymph nodes, surgery due to intestinal obstruction (ileus)
• Patient agrees to the preservation of tumor material for the purpose of molecular analyzes including the determination of the genetic profile of the tumor (participation in the project "RESIST")

Exclusion Criteria

• Preoperative Radiotherapy
• Preoperative chemotherapy
• Heart failure> Grade II (functional NYHA classification)
• Existing concomitant disease or condition that would make the patient unsuitable for a study participation or interfere with the safety of the subject
• Any psychological, familial, sociological or geographical event which does not allow observance of the study protocol
• Additional carcinoma therapy (chemotherapy, radiation, biological therapy, immunotherapy or hormonal therapy) during the study
• Known malignant second neoplasia within the last 5 years (except for a basal cell carcinoma or a carcinoma in situ of the uterine cervix).

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Chemotherapy plus targeted treatment	targeted substance according to the avatar model	Patients are treated in second-line with chemotherapy plus a targeted treatment according to the resistance mechanism to cetuximab pretreatment

Primary Outcome Measures

Name	Time	Method
Progression-free-survival	5-7 months	according to RECIST 1.1

Trial Locations

Locations (1)

University of Munich - Klinikum der Universitaet Muenchen; 🇩🇪 Munich, Bavaria, Germany