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AzTrials

NSCLC Stage IIIBPhase 2NCT05281406

Additional Chemotherapy for EGFRm Patients with the Continued Presence of Plasma CtDNA EGFRm At Week 3 After Start of Osimertinib 1st-line Treatment (PACE-LUNG)

A Phase 2 study testing Osimertinib, Pemetrexed and Cisplatin in people with NSCLC Stage IIIB and NSCLC Stage IV, run by Goethe University at 16 sites in Germany.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

PACE is a prospective multicenter single-arm investigator-initiated phase II trial that examines the value of a treatment escalation strategy by the addition of platinum-based doublet chemotherapy to osimertinib in patients with treatment-naïve NSCLC harboring L858R or del19 EGFR mutation who are suspected to have… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
NSCLC Stage IIIB, NSCLC Stage IV
What is being tested?
Osimertinib, Pemetrexed and Cisplatin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
16 sitesGermany
Study dates
12 Nov 2021to Nov 2026
Phase
Phase 2
Are there results?
Not yet: the study is under way

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

  • Pre-Screening Phase
  • Provision of written informed consent for the pre-screening phase.
  • Age ≥ 18 years
  • Histologically confirmed stage IIIB or IV NSCLC
  • Tumor positive for Ex19del or L858R EGFR mutation assessed according to local standard.
  • Planned treatment with osimertinib 80mg/d 1st-line as SoC or ongoing treatment for a maximum of 28 days
Show all 20Show fewer
  • Available radiographic chest and abdominal CT or MRI scans performed up to 42 days before initial osimertinib treatment
  • Previously untreated with systemic treatment given as primary therapy for advanced or metastatic disease, except for osimertinib for a maximum of 28 days (see above)
  • At least one measurable site of disease as defined by RECISTv1.1 criteria
  • Female subjects of childbearing potential (WOCBP) should be using highly effective contraceptive measures and must have a negative urine or serum pregnancy test within 7 days prior to start of study treatment and must not be breast-feeding prior to start of trial. Further information in Appendix 20.7 (Definition of Women of Childbearing Potential and Acceptable Contraceptive Methods)
  • Non-child-bearing potential must be evidenced 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 considered 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
  • Treatment Phase
  • Provision of informed consent for the screening and treatment phase prior to any study specific procedures, including screening evaluations that are not SoC.
  • Persistent mEGFR ctDNA signal 21 to 28 days after osimertinib initiation for advanced of metastatic ex19del or L858R EGFR mutation positive NSCLC as assessed by a liquid biopsy during the pre-screening phase of the trial in the central laboratory.
  • ECOG performance status 0-2.
  • The patient is willing and able to comply with the protocol for the duration of the study, including hospital visits for treatment and scheduled follow-up visits and examinations.
  • Osimertinib no longer than 10 weeks before start of chemotherapy in the treatment phase

Who cannot join

  • Pre-Screening Phase
  • History of another primary malignancy. Exceptions are:
  • Malignancy treated with curative intent and with no known active disease ≥6 months before the first dose of IMP, and of low potential risk for recurrence
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
  • Adequately treated carcinoma in situ without evidence of disease
  • History of leptomeningeal carcinomatosis
Show all 39Show fewer
  • Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study, or during the follow-up period of an interventional study
  • Previous enrolment in the present study.
  • Treatment Phase
  • Symptomatic CNS metastases. [Patients with asymptomatic brain metastases may be included.]
  • History of leptomeningeal carcinomatosis
  • Currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be strong inducers of CYP3A4 (at least 3 weeks prior) (Appendix 20.5). All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer effects on CYP3A4.
  • Osimertinib had to be withheld or administered at reduced dosage for toxicity management for more than 7 days or persistent unresolved toxicities which preclude study treatment.
  • Any unresolved toxicities other than osimertinib from prior therapy greater than CTCAE grade 1 at the time of starting study treatment, with the exception of alopecia and grade 2 prior platinum-therapy-related neuropathy.
  • History of hypersensitivity to active or inactive excipients of osimertinib or drugs with a similar chemical structure or class to osimertinib. History of hypersensitivity to any of the chemotherapy drugs used.
  • 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 jeopardize compliance with the protocol, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required.
  • 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.
  • Any of the following cardiac criteria:
  • Mean resting corrected QT interval (QTc) > 470 msec obtained from 3 electrocardiograms (ECGs), using 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 and second degree heart block.
  • Patient with any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, electrolyte abnormalities (including: Serum/plasma potassium < LLN; Serum/plasma magnesium < LLN; Serum/plasma calcium < LLN), 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 and cause Torsades de Pointes. [Note: Electrolyte abnormalities (hypokalaemia, hypomagnesaemia, hypocalcaemia) can be corrected to be within normal ranges prior to first dose. No more than two re-tests may be performed in order to meet this criterion.]
  • Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease.
  • Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
  • Absolute neutrophil count below lower limit of normal (<LLN) *
  • Platelet count below lower limit of normal (<LLN) *
  • Hemoglobin <90 g/L *
  • The use of granulocyte colony stimulating factor support, platelet transfusion and blood transfusions to meet these criteria is not permitted.
  • Alanine aminotransferase >2.5 times 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;
  • Serum creatinine >1.5 times ULN concurrent with creatinine clearance <60 mL/min [calculated by Cockcroft and Gault equation]-confirmation of creatinine clearance is only required when creatinine is >1.5 times ULN.
  • INR ≤ 1.4 or aPTT ≤ 40 sec during the last 7 days before chemotherapy [Subjects under therapeutic anticoagulation are permitted.]
  • Judgement 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.
  • Women who are pregnant or breast-feeding
  • Male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 4 months (male patients) or 6 weeks (female patients) after the last dose of osimertinib and 6 months after the last dose of chemotherapy.
  • Patients who are unable to consent because they do not understand the nature, significance and implications of the clinical trial and therefore cannot form a rational intention in the light of the facts [§ 40 Abs. 1 S. 3 Nr. 3a AMG].
  • Treatment with an investigational drug within five half-lives of the compound or 3 months, whichever is greater.
  • Any chemotherapy, biologic, or hormonal therapy for cancer treatment used concurrently or within 6 months prior to first dose of study treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
  • Major surgery (as defined by the Investigator) within 4 weeks prior to starting the study; patients must have recovered from effects of preceding major surgery. Note: Local non-major surgery for palliative intent (e.g., surgery of isolated lesions) is acceptable

Trial locations and contacts

16 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Martin Sebastian, MD contact

+49(0)69 6301 ext. 5677

martin.sebastian@kgu.de

Jan Stratmann, MD contact

+49(0)69 6301 ext. 5677

jan.stratmann@kgu.de

16 sites in 1 country

Germany16 sites, 16 recruiting

  • Charité Universitätsmedizin Berlin Campus Virchow Klinikum Klinik mit Schwerpunkt Infektiologie und Pneumologie

    Berlin, 13353

    Nikolaj Frost, PD Dr.

    Recruiting

  • Universitätsklinik Köln, Lung Cancer Group Cologne - Innere Medizin I

    Cologne, 50937

    Sebastian Michels, Dr.

    Recruiting

  • Technische Universität Dresden Medizinische Fakultät Carl Gustav Carus Medizinische Klinik und Poliklinik I

    Dresden, 01307

    Martin Wermke, PD Dr.

    Recruiting

  • Universitätsklinikum Essen, Westdeutsches Tumorzentrum - Innere Klinik

    Essen, 45147

    Marcel Wiesweg, PD Dr.

    Recruiting

  • University Hospital Frankfurt

    Frankfurt, 60590

    Martin Sebastian, MD

    Recruiting

  • Asklepios Lungenklinik Gauting

    Gauting, 82131

    Niels Reinmuth, Prof. Dr.

    Recruiting

  • MVZ II der Niels Stensen Kliniken; Franziskus Hospital Harderberg

    Georgsmarienhütte, 49124

    Petra Hoffknecht, Dr.

    Recruiting

  • Universitätsmedizin Göttingen, Klinik für Hämatologie und Medizinische Onkologie

    Göttingen, 37075

    Tobias Overbeck, Dr.

    Recruiting

  • Krankenhaus Martha-Maria Halle-Dölau Klinik für Innere Medizin II

    Halle, 06120

    Wolfgang Schütte, Prof. Dr.

    Recruiting

  • Universitätsklinikum Hamburg-Eppendorf Hubertus Wald Tumorzentrum - UCCH II. Medizinische Klinik und Poliklinik

    Hamburg, 20246

    Janna-Lisa Velthaus, Dr.

    Recruiting

  • Universitätsklinikum Heidelberg, Thoraxklinik Heidelberg gGmbH

    Heidelberg, 69126

    Farastuk Bozorgmehr, Dr.

    Recruiting

  • DGD Lungenklinik Hemer

    Hemer, 58675

    Karsten Schulmann, PD Dr.

    Recruiting

  • Universitätsmedizin der Johannes Gutenberg-Universität Mainz

    Mainz, 55131

    Jürgen Alt, Dr.

    Recruiting

  • LMU-München Pneumologie und Thorakale Onkologie Medizinische Klinik V; Innenstadt

    München, 80336

    Amanda Tufman, PD Dr.

    Recruiting

  • Klinikum Nürnberg Nord Paracelsus Med. Privat Universität Pneumologie und Lungentumorzentrum

    Nuremberg, 90419

    Wolfgang Brückl, Prof. Dr.

    Recruiting

  • Pius Hospital Oldenburg Medizinischer Campus Universität Oldenburg

    Oldenburg, 26121

    Frank Griesinger, Prof. Dr.

    Recruiting

Other trials in Germany

About this study

PACE is a prospective multicenter single-arm investigator-initiated phase II trial that examines the value of a treatment escalation strategy by the addition of platinum-based doublet chemotherapy to osimertinib in patients with treatment-naïve NSCLC harboring L858R or del19 EGFR mutation who are suspected to have poor response upon single-agent TKI treatment.

Read the detailed description

Hypothesize, that in patients with on-label osimertinib 1st-line treatment of stage IIIB or IV NSCLC, a biomarker-driven escalation of osimertinib therapy with a platinum-based chemotherapy regimen will effectively enhance PFS and subsequently OS. Lack of EGFRm clearance after an osimertinib treatment period of 3 weeks as assessed by liquid biopsy will be used to predict sub-optimal response. In these patients, treatment will be escalated after approx. 7 weeks of on-label osimertinib monotherapy by adding up to 4 cycles of a combination regimen of pemetrexed and cisplatin or carboplatin. Patients with complete EGFR plasma clearance will continue to receive standard of care osimertinib and will not be eligible for the study. Primary outcome measure will be PFS, which will be compared to historical data on TKI monotherapy from persistent EGFR shedder from the FLAURA trial.

Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

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

  • OsimertinibDrug

    Also called Tagrisso

    80 mg daily or reduced dose 40 mg daily

  • PemetrexedDrug

    500 mg/m² i.v. d1 of every 21-day cycle for a maximum of 4 cycles

  • CisplatinDrug

    75mg/m² i.v. d1 of every 21-day cycle for a maximum of 4 cycles

  • CarboplatinDrug

    AUC 5 mg/mL/min i.v. d1 of every 21-day cycle for a maximum of 4 cycles

Study groups in NCT05281406
Study groupRoleWhat they receive
Osimertinib in combination with platinum-based chemotherapyExperimentalall patients received a platinum-based chemotherapy (carboplatin/pemetrexed or cisplatin/pemetrexed) for a maximum of 4 cycles (q3w) in combination with 80 mg Osimertinib daily
Receives: Drug: Osimertinib; Drug: Pemetrexed; Drug: Cisplatin; Drug: Carboplatin

What is being measured

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

  1. Progression Free Survival (PFS1)

    Progression Free Survival using investigator assessments according to Response Evaluation Criteria in Solid Tumours (RECIST 1.1) defined as number of months from first dose of chemotherapy until last follow-up, PD, death or withdrawal of consent.

    Measured: 2 years

Secondary outcomes (6)

  1. Progression Free Survival (PFS0)

    Progression Free Survival using investigator assessments according to Response Evaluation Criteria in Solid Tumours (RECIST 1.1) defined as number of months from first dose of osimertinib until last follow-up, PD, death or withdrawal of consent.

    Measured: for a minimum of 24 months from inclusion

  2. Overall Survival (OS1)

    OS1 Survival will be calculated from the first dose of chemotherapy until the date of death from any cause. If no event is observed (e.g. lost to follow-up) OS is censored at the day of last subject contact.

    Measured: for a minimum of 24 months from inclusion

  3. Overall Survival (OS0)

    OS0 Survival will be calculated from the date of start of osimertinib until the date of death from any cause. If no event is observed (e.g. lost to follow-up) OS is censored at the day of last subject contact.

    Measured: for a minimum of 24 months from inclusion

  4. Incidence of treatment related Adverse Events (Safety and Tolerability)

    Frequency and severity of Adverse Events, grading according to CTCAE V5.0

    Measured: up to 16 weeks from start of study treatment

  5. Measurement of Quality of Life with PRO-CTCAE. questionnaire

    Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) minimum value: not at all (1); maximum value: severe (5); higher scores mean a worse outcome

    Measured: up to 16 weeks from start of study treatment

  6. Measurement of Quality of Life with EORTC QLQ-C30 questionnaire

    The European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30) minimum value: not at all (1); maximum value: very much (4); higher scores mean a worse outcome

    Measured: up to 16 weeks from start of study treatment

Timeline

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

  1. First posted16 Mar 2022
  2. Study start12 Nov 2021
  3. Primary completionNov 2025 (estimated)
  4. Study completionNov 2026 (estimated)

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
Phase II prospective non-randomized biomarker-enriched single arm trial
Masking
None (open label)
Enrolment
50 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05281406
Sponsor's protocol ID
PACE LUNG
Status last verified
Feb 2025
First submitted
1 Feb 2022
Last updated
21 Feb 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Osimertinib, Pemetrexed and Cisplatin in people with NSCLC Stage IIIB and NSCLC Stage IV, run by Goethe University at 16 sites 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 20 inclusion and 39 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: looking for participants now, as of the sponsor's last update on 21 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites 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?

This study is still under way. Results are not available in the source record yet.

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

Contact Martin Sebastian, MD (+49(0)69 6301 ext. 5677, martin.sebastian@kgu.de), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival (PFS1) (time frame: 2 years). 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 NCT05281406.

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 21 Feb 2025.

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