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

NCT03263663 | Unknown

• 1 other identifier: RESIST
• Study Type: observational
• Target: 1,000
• Locations: 1 country
• Sites: 1

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

Keywords

colorectal cancer; adjuvant

Outcome Measures

Primary Outcomes (1)

• Progression-free-survival

  according to RECIST 1.1

  5-7 months

Study Arms (2)

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

Chemotherapy according to physician choice standard

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

Interventions

targeted substance according to the avatar model DRUG

individualized second line treatment

Chemotherapy plus targeted treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

locally advanced colorectal cancer

You may qualify if:

• 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")

You may not qualify if:

• 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).

Sponsors & Collaborators

• PD Dr. med. Volker Heinemann: lead
• MGO Ruhr-University Bochum (RUB): collaborator

Study Sites (1)

University of Munich - Klinikum der Universitaet Muenchen

Munich, Bavaria, 81379, Germany

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Primary tumormaterial

MeSH Terms

Conditions

Colonic Neoplasms; Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Sebastian Stintzing, Prof. Dr.

  Senior Physician

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sebastian Stintzing, Prof. Dr.

CONTACT

+49 89 4400 0; sebastian.stintzing@med.uni-muenchen.de

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of the CCC LMU

Study Record Dates

• First Submitted: August 24, 2017
• First Posted: August 28, 2017
• Study Start: January 1, 2017
• Primary Completion: January 1, 2021
• Study Completion: January 1, 2025
• Last Updated: August 28, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will share

Locations

DE (1)