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

NCT ID: NCT03263663

Last Updated: 2017-08-28

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 1000 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2017-01-01
• Study Completion Date: 2025-01-01

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.

Conditions

Colo-rectal Cancer; RAS Wild-type; UICC III; UICC II + RF; UICC IV Curative Intent

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

Chemotherapy plus targeted treatment

Patients are treated in second-line with chemotherapy plus a targeted treatment according to the resistance mechanism to cetuximab pretreatment

targeted substance according to the avatar model

Intervention Type: DRUG

individualized second line treatment

Chemotherapy according to physician choice standard

Patients are treated in second-line with chemotherapy according to physicians choice after cetuximab pretreatment

No interventions assigned to this group

Interventions

targeted substance according to the avatar model

individualized second line treatment

Intervention Type: DRUG

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

MGO Ruhr-University Bochum (RUB)

UNKNOWN

Sponsor Role: collaborator

PD Dr. med. Volker Heinemann

OTHER

Sponsor Role: lead

Responsible Party

PD Dr. med. Volker Heinemann

Director of the CCC LMU

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Sebastian Stintzing, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

Senior Physician

Locations

University of Munich - Klinikum der Universitaet Muenchen

Munich, Bavaria, Germany

Site Status: RECRUITING

Countries

Germany

Central Contacts

Sebastian Stintzing, Prof. Dr.

Role: CONTACT

sebastian.stintzing@med.uni-muenchen.de

+49 89 4400 0

Facility Contacts

Sebastian Stintzing, Prof. Dr.

Role: primary

sebastian.stintzing@med.uni-muenchen.de

+49 89 4400 0

Other Identifiers

RESIST

Identifier Type: -

Identifier Source: org_study_id