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NSCLCPhase 2NCT03810066

Exploring the Theragnostic Value of Osimertinib in EGFR-mutated Lung Cancer (THEROS)

A Phase 2 study testing Osimertinib in people with NSCLC and EGFR T790M, run by University Hospital, Essen at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a single arm, open label, multicentric proof-of-concept, phase II study in patients with EGFR-mutated non-small-cell lung cancer (NSCLC) with acquired TKI resistance who are "unknown" for EGFR T790M status due to non-informative or unfeasible tumor rebiopsy, and a negative finding for EGFR T790M in a standard… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
NSCLC, EGFR T790M, FDG-PET
What is being tested?
Osimertinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
1 siteGermany
Study dates
3 Jun 2019to 30 Sep 2022
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Provision of informed consent prior to any study specific procedures
  • Patients (male/female) must be > 18 years of age.
  • EGFR-mutated NSCLC not amenable to curative treatment (surgery, curative radiochemotherapy).
  • Acquired resistance to a first- or second-generation EGFR-TKI (e.g. afatinib, erlotinib, gefitinib) following initial benefit (defined as objective response, or stable disease for at least 3 months)
  • No tumor rebiopsy available or negative result for EGFR T790M mutation status by a SoC molecular pathology test (e.g. Sanger sequencing, PCRbased genotyping, deep sequencing) of a rebiopsy of a progressive tumor lesion
  • Negative finding from EGFR T790M mutation testing in plasma-derived DNA using a SoC assay (e.g. Roche Cobas)
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  • At least one tumor lesion with significant FDG uptake as determined by PET/CT scanning prior to study treatment
  • Consent to the research use of donated biological samples.
  • World Health Organization (WHO) performance status 0-2.
  • Patients must have a life expectancy ≥ 12 weeks.
  • Females should be using adequate contraceptive measures, should not be breast feeding and must have a negative pregnancy test prior to start of dosing if of childbearing potential, which will be repeated on a monthly basis, or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:
  • Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments
  • Women under 50 years old would be consider postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the post-menopausal range for the institution
  • Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
  • Male patients should be willing to use barrier contraception (see Restrictions, Section 3.6).
  • Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

Who cannot join

  • EGFR-mutated NSCLC and demonstration of the T790M resistance mutation by standard assay technology in tumor-derived or plasma-derived DNA
  • Absence of a tumor lesion with significant FDG uptake at PET/CT scanning prior to study treatment
  • Involvement in the planning and/or conduct of the study (applies to both sponsor staff and/or staff at the study site)
  • Previous treatment with osimertinib or any experimental or approved mutationspecific EGFR-TKI with clinical activity against the EGFR T790M resistance mutation
  • Treatment with an investigational drug within one week or five drug half-lives (whichever is longer) of the compound (3 weeks for antibodies)
  • Patients currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be potent inducers of CYP3A4 (at least 3 week prior) (Appendix A - Guidance regarding Potential Interactions With Concomitant Medications). All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer effects on CYP3A4. A list for drug interaction potential is found in section 5.1.6.4 of the osimertinib IB.
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  • Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study Treatment with the exception of alopecia and grade 2, prior chemotherapy related neuropathy.
  • Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardise compliance with the protocol, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required.
  • Patients with symptomatic CNS metastases who are neurologically unstable
  • Past medical history of ILD, drug-induced ILD, radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD
  • Fasting blood glucose levels above 150 mg/dl (precluding informative FDGPET/ CT scanning)
  • Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
  • Absolute neutrophil count <1.5 x 109/L Platelet count <100 x 109/L Haemoglobin <90 g/L Alanine aminotransferase >2.5 times the upper limit of normal (ULN) if no demonstrable liver metastases or >5 times ULN in the presence of liver metastases Aspartate aminotransferase >2.5 times ULN if no demonstrable liver metastases or >5 times ULN in the presence of liver metastases Total bilirubin >1.5 times ULN if no liver metastases or >3 times ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinaemia) or liver metastases Creatinine >1.5 times ULN concurrent with creatinine clearance <50 ml/min (measured or calculated by Cockcroft and Gault equation); confirmation of creatinine clearance is only required when creatinine is >1.5 times ULN.
  • Any of the following cardiac criteria:
  • Mean resting corrected QT interval (QTc using Fredericia's formula) > 470 msec obtained from the screening clinic ECG machine-derived QTc value
  • Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block)
  • Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, electrolyte abnormalities (including serum/plasma potassium level below lower level of normal), congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval
  • Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of osimertinib
  • History of hypersensitivity to osimertinib (or drugs with a similar chemical structure or class to osimertinib) or any excipients of these agents
  • Males and females of reproductive potential who are not using an effective method of birth control and females who are pregnant or breastfeeding or have a positive (urine or serum) pregnancy test prior to study entry
  • Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • Prof. Dr. med. Martin Schuler

    Essen, North Rhine-Westphalia, 45147

Other trials in Germany

About this study

Official title: Exploring the Theragnostic Value of Osimertinib in EGFR-mutated Lung Cancer (THEROS) - A Multicentric Phase II Study in Patients With TKI-resistant EGFR-mutated Lung Cancer Exhibiting Early Metabolic Response to Osimertinib

This is a single arm, open label, multicentric proof-of-concept, phase II study in patients with EGFR-mutated non-small-cell lung cancer (NSCLC) with acquired TKI resistance who are "unknown" for EGFR T790M status due to non-informative or unfeasible tumor rebiopsy, and a negative finding for EGFR T790M in a standard plasma genotyping assay. All patients will receive osimertinib as continuous oral treatment for one cycle (28 days). Patients who demonstrate a metabolic response by FDG-PET scanning (to be conducted between day 15 and day 28 of cycle 1) will continue treatment until clinical or radiological progression. Osimertinib treatment will be terminated in patients not experiencing a metabolic response.

Primary objective:

To study the rate of early metabolic responses to osimertinib in patients with EGFR-mutated NSCLC and acquired TKI resistance who are "unknown" for EGFR T790M status due to non-informative or unfeasible tumor rebiopsy, and a negative finding for EGFR T790M in a standard plasma genotyping assay.

Being tested
Osimertinib

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • OsimertinibDrug

    All patients will be treated with osimertinib 80 mg/d for one cycle (28 days).

Study groups in NCT03810066
Study groupRoleWhat they receive
OsimertinibExperimentalNot described
Receives: Drug: Osimertinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Rate of metabolic responses

    Rate of metabolic responses as detected by FDG-PET before end of cycle 1. One cycle is defined as 28 days continuous treatment.

    Measured: 28 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Jan 2019
  2. Study start3 Jun 2019
  3. Primary completion31 Dec 2021
  4. Study completion30 Sep 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Simon 2 step design
Masking
None (open label)
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03810066
Sponsor's protocol ID
THEROS
Status last verified
May 2024
First submitted
10 Jan 2019
Last updated
9 May 2024
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Schuler M, Hense J, Darwiche K, Michels S, Hautzel H, Kobe C, Lueong S, Metzenmacher M, Herold T, Zaun G, Laue K, Drzezga A, Theegarten D, Nensa F, Wolf J, Herrmann K, Wiesweg M. Early Metabolic Response by PET Predicts Sensitivity to Next-Line Targeted Therapy in EGFR-Mutated Lung Cancer with Unknown Mechanism of Acquired Resistance. J Nucl Med. 2024 Jun 3;65(6):851-855. doi: 10.2967/jnumed.123.266979.

    PubMed 38575188

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Osimertinib in people with NSCLC and EGFR T790M, run by University Hospital, Essen at 1 site in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rate of metabolic responses (time frame: 28 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03810066, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 May 2024.

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