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)

NCT05281406 | Recruiting Phase 2 DMC

• 1 other identifier: PACE LUNG
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 16

Brief 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 poor response upon single-agent TKI treatment.

Conditions

NSCLC Stage IIIB; NSCLC Stage IV

Outcome Measures

Primary Outcomes (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.

  2 years

Secondary Outcomes (6)

• Progression Free Survival (PFS0)

  for a minimum of 24 months from inclusion

• Overall Survival (OS1)

  for a minimum of 24 months from inclusion

• Overall Survival (OS0)

  for a minimum of 24 months from inclusion

• Incidence of treatment related Adverse Events (Safety and Tolerability)

  up to 16 weeks from start of study treatment

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

  up to 16 weeks from start of study treatment

Study Arms (1)

Osimertinib in combination with platinum-based chemotherapy

EXPERIMENTAL

all 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

Drug: Osimertinib; Drug: Pemetrexed; Drug: Cisplatin; Drug: Carboplatin

Interventions

Osimertinib DRUG

80 mg daily or reduced dose 40 mg daily

Also known as: Tagrisso

Osimertinib in combination with platinum-based chemotherapy

Pemetrexed DRUG

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

Osimertinib in combination with platinum-based chemotherapy

Cisplatin DRUG

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

Osimertinib in combination with platinum-based chemotherapy

Carboplatin DRUG

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

Osimertinib in combination with platinum-based chemotherapy

Eligibility Criteria

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

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Goethe University: lead

Study Sites (16)

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

Berlin, 13353, Germany

RECRUITING

Universitätsklinik Köln, Lung Cancer Group Cologne - Innere Medizin I

Cologne, 50937, Germany

RECRUITING

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

Dresden, 01307, Germany

RECRUITING

Universitätsklinikum Essen, Westdeutsches Tumorzentrum - Innere Klinik

Essen, 45147, Germany

RECRUITING

University Hospital Frankfurt

Frankfurt, 60590, Germany

RECRUITING

Asklepios Lungenklinik Gauting

Gauting, 82131, Germany

RECRUITING

MVZ II der Niels Stensen Kliniken; Franziskus Hospital Harderberg

Georgsmarienhütte, 49124, Germany

RECRUITING

Universitätsmedizin Göttingen, Klinik für Hämatologie und Medizinische Onkologie

Göttingen, 37075, Germany

RECRUITING

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

Halle, 06120, Germany

RECRUITING

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

Hamburg, 20246, Germany

RECRUITING

Universitätsklinikum Heidelberg, Thoraxklinik Heidelberg gGmbH

Heidelberg, 69126, Germany

RECRUITING

DGD Lungenklinik Hemer

Hemer, 58675, Germany

RECRUITING

Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Mainz, 55131, Germany

RECRUITING

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

München, 80336, Germany

RECRUITING

Klinikum Nürnberg Nord Paracelsus Med. Privat Universität Pneumologie und Lungentumorzentrum

Nuremberg, 90419, Germany

RECRUITING

Pius Hospital Oldenburg Medizinischer Campus Universität Oldenburg

Oldenburg, 26121, Germany

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

osimertinib; Pemetrexed; Cisplatin; Carboplatin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals

Study Officials

• Martin Sebastian, MD

  Goethe University Frankfurt

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Martin Sebastian, MD

CONTACT

+49(0)69 6301; martin.sebastian@kgu.de

Jan Stratmann, MD

CONTACT

+49(0)69 6301; jan.stratmann@kgu.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Phase II prospective non-randomized biomarker-enriched single arm trial

Study Record Dates

• First Submitted: February 1, 2022
• First Posted: March 16, 2022
• Study Start: November 12, 2021
• Primary Completion: November 1, 2025
• Study Completion (Estimated): November 1, 2026
• Last Updated: February 21, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

DE (16)