Optimization of Individualized Therapy for CRCs With Secondary RESISTance Towards Anti-EGFR Targeted Therapy Using an Avatar Model (2016-003295-46)

Optimization of Individualized Therapy for CRCs With Secondary RESISTance Towards Anti-EGFR Targeted Therapy Using an Avatar Model (Colon-Resist-Net)

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.

Study Overview

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

• Study Type: Observational
• Enrollment (Anticipated): 1000

Contacts and Locations

• Study Contact: Name: Sebastian Stintzing, Prof. Dr.; Phone Number: +49 89 4400 0; Email: sebastian.stintzing@med.uni-muenchen.de

Study Locations

• Germany
  • Bavaria
    • Munich, Bavaria, Germany, 81379
      • Recruiting
      • University of Munich - Klinikum der Universitaet Muenchen
      • Contact: Sebastian Stintzing, Prof. Dr.; Phone Number: +49 89 4400 0; Email: sebastian.stintzing@med.uni-muenchen.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

locally advanced colorectal cancer

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Chemotherapy plus targeted treatment; Patients are treated in second-line with chemotherapy plus a targeted treatment according to the resistance mechanism to cetuximab pretreatment	Drug: targeted substance according to the avatar model; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free-survival	according to RECIST 1.1	5-7 months

Collaborators and Investigators

• Sponsor: PD Dr. med. Volker Heinemann
• Collaborators: MGO Ruhr-University Bochum (RUB)
• Investigators: Principal Investigator: Sebastian Stintzing, Prof. Dr., Senior Physician

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Anticipated): January 1, 2021
• Study Completion (Anticipated): January 1, 2025

Study Registration Dates

• First Submitted: August 24, 2017
• First Submitted That Met QC Criteria: August 24, 2017
• First Posted (Actual): August 28, 2017

Study Record Updates

• Last Update Posted (Actual): August 28, 2017
• Last Update Submitted That Met QC Criteria: August 24, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: colorectal cancer; adjuvant
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms
• Other Study ID Numbers: RESIST

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No