Status and phase
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About
This study will compare the effectiveness of osimertinib alone with the combination of osimertinib and chemotherapy (carboplatin and pemetrexed) in people with metastatic lung cancer that has a change (mutation) in the gene EGFR. Osimertinib alone is the usual treatment for metastatic EGFR-mutant lung cancer. Researchers think adding chemotherapy to osimertinib could possibly add to the anticancer effects of the usual treatment and help stop cancer from growing or spreading.
Full description
Screening portion:
Patients will begin on single agent osimertinib obtained commercially at the standard dose of 80mg orally daily. Osimertinib monotherapy is currently standard of care first-line treatment for patients with metastatic EGFR-mutant lung cancers. During the screening portion of the study, patients will be treated per standard practice as decided by the treating physician using the guidance of the osimertinib product label. The patient will proceed with three cycles (21 days per cycle) of single agent osimertinib. Patients will be seen on C1D1 for osimertinib start (telemedicine visits for C1D1 assessments are acceptable)
Randomization/treatment portion:
Patients will be randomized to continue osimertinib alone (Arm A) or addition of carboplatin/pemetrexed chemotherapy to osimertinib (Arm B).Randomization will be accomplished by the method of random permuted block and patients will be stratified by type of EGFR mutation (EGFR exon 19/EGFR L858R or other) and presence of CNS metastases (absent, present). Randomization will occur after data is available to identify the patients with persistent EGFR ctDNA detected in the C2D1 plasma sample; only patients with persistent EGFR ctDNA will be randomized. Subject's eligibility prior to randomization will be at the discretion of the individual sites enrolling the patients. EGFR mutation can be confirmed at outside institutions: while pathology confirmation will occur at the enrolling institution, the required documentation of EGFR can occur internal or external to the enrolling institution. For those patients without detectable ctDNA at C2D1, the end of treatment assessments will not include CT scan or ctDNA sampling.
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
Inclusion Criteria: Inital
Age ≥ 18 years
Biopsy proven metastatic non-small cell lung cancer, confirmed at enrolling institution
Somatic activating mutation in EGFR in pre-treatment tumor biopsy/ cytology from pleural fluid or cfDNA
Either have not started a prior EGFR TKI therapy or may have started osimertinib within 3 weeks of confirming eligibility and enrollment criteria of measurable disease per approval of PI, with no prior chemotherapy for treatment of metastatic disease (adjuvant therapy > 6 months prior to study start is acceptable)
Measurable (RECIST 1.1) indicator lesion not previously irradiated with measurable disease determined per treating investigator. If a patient has already started on osimertinib there must be available pre-osimertinib baseline tumor assessments, to be utilized for RECIST 1.1 assessment.
Karnofsky performance status (KPS)≥70%,
Ability to swallow oral medications
Adequate organ function (use of G-CSF and/or transfusion to meet these criteria are not allowed)
Willing to use highly effective contraceptive measures if of child-bearing potential or if the patient's sexual partner is a woman of child-bearing potential:
Exclusion Criteria: Initial
Pregnant or lactating women
Any radiotherapy within 1 week prior to starting treatment on protocol. The washout window only applies for patients who have not started Osimertinib.
Any major surgery within 2 weeks of starting treatment on protocol. The washout window only applies for patients who have not started Osimertinib.
Any evidence of clinically significant interstitial lung disease
Treatment with an investigational drug within five half-lives of the compound or 3 months, whichever is greater
Currently receiving (or unable to stop prior to receiving the first dose of study treatment) medications or herbal supplements known to be strong inducers of CYP3A4. All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer effects on CYP3A4.
Any unresolved toxicities 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
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
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 tablets or previous significant bowel resection that would preclude adequate absorption of osimertinib.
Any of the following cardiac criteria:
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.
History of hypersensitivity to active or inactive excipients of osimertinib or drugs with a similar chemical structure or class to osimertinib.
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.
Inclusion Criteria: Randomization
Patients with detectable plasma EGFR mutations at C2D1
Karnofsky performance status (KPS) ≥ 70%
Adequate organ function
Please note: All 'Initial' Exclusion Criteria must be re-confirmed prior to randomization.
Primary purpose
Allocation
Interventional model
Masking
571 participants in 2 patient groups
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Central trial contact
Gregory Riely, MD, PhD; Helena Yu, MD
Data sourced from clinicaltrials.gov
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