ctDNA Guided Treatment of Early Resistance to Targeted Treatment

NCT04148066 | Completed

• 1 other identifier: M18TAT
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 2

Brief Summary

The current strategy is to test for treatment resistance at the time of radiological progression and design subsequent treatment based on the mechanism of resistance. However, upon disease progression patients tend to deteriorate quickly and 30% - 40% of patients will not be in the clinical condition to receive next line treatment. Therefore, there is a potential for early resistance identification and directing treatment against it in order to improve patient outcome.

Conditions

Carcinoma, Non-Small-Cell Lung

Outcome Measures

Primary Outcomes (1)

• percentage of patients in which a drug resistant clone can be detected with ctDNA

  To identify the percentage of patients in which a drug resistant clone can be detected with ctDNA before the emergence of radiological progression.

  Trough study completion, an average of 2 years

Secondary Outcomes (1)

• the success rate of crizotinib and osimertinib combination treatment to eliminate MET amplification

  Trough study completion, an average of 2 years

Study Arms (1)

Osimertinib and Crizotinib

OTHER

Osimertinib will be administered according to label: 80 mg once daily. Crizotinib will only be prescribed upon detection of MET amplification using ctDNA. Crizotinib will be administered according to label: 250 mg bi-daily.

Diagnostic Test: ctDNA blood sample

Interventions

ctDNA blood sample DIAGNOSTIC_TEST

every six weeks during treatment and upon radiological progression blood will be drawn to analyse ctDNA with Avenio ctDNA (Expanded panel) to detect all known EGFR TKI resistance mechanisms.

Osimertinib and Crizotinib

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed metastatic NSCLC, characterized by a sensitizing exon 19 deletion or exon 21 L858R EGFR mutation.
• WHO performance status 0-2.
• Eligible for osimertinib treatment according to the label and according to the treating physician.
• Patients must be ≥18 years of age.

You may not qualify if:

• \. Patients with symptomatic central nervous system metastases who are neurologically unstable. Unstable brain metastases except for those who have completed definitive therapy and have had a stable neurological status for 2 weeks after completion of definitive therapy. Patients may be on corticosteroids to control brain metastases if they have been on a stable dose for 2 weeks prior to the start of study treatment and are clinically asymptomatic.

Sponsors & Collaborators

• The Netherlands Cancer Institute: lead
• Roche Pharma AG: collaborator

Study Sites (2)

The Netherlands Cancer Institute-Antoni van Leeuwenhoek

Amsterdam, North Holland, 1066 CX, Netherlands

Location

Erasmus MC, Universitair Medisch Centrum Rotterdam

Rotterdam, Netherlands

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• J de Langen, MD, PhD

  The Netherlands Cancer Institute-Antoni van Leeuwenhoek

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 30, 2019
• First Posted: November 1, 2019
• Study Start: July 17, 2019
• Primary Completion: December 17, 2021
• Study Completion: December 17, 2021
• Last Updated: October 10, 2023

Record last verified: 2023-10

Locations

NL (2)