Clinical Trial 21074

• Overview

  Study Title:

  A Phase 2 Randomized Study of Osimertinib Versus Osimertinib Plus Chemotherapy for Patients with Metastatic EGFR-Mutant Lung Cancers That Have Detectable EGFRMutant cfDNA in Plasma After Initiation of Osimertinib

  Summary:

  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.

  Objective:

  Primary Objective: Determine the progression-free survival of osimertinib versus osimertinib, carboplatin and pemetrexed in patients with metastatic EGFR mutant lung cancers with persistent detectable EGFR mutations in plasma despite initiation of osimertinib Secondary objectives: 1) overall response rate 2) overall survival 3) progression-free survival at 12 months 4) clearance of plasma EGFR mutations 5) intracranial progression-free survival 6) identify resistance mechanisms to study treatment 7) safety and tolerability of the treatment

• Treatments

  Therapies:

  Chemotherapy (NOS); Therapy (NOS)

  Medications:

  AZD9291 (Osimertinib); Alimta (Pemetrexed); Osimertinib (); Paraplatin (carboplatin); Pemetrexed (); carboplatin ()

• Inclusion Criteria

  Inclusion Criteria:
  • Age 18 years or older.
  • 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:
  • Other criteria may apply

• Exclusion Criteria

  > Pregnant or lactating women
  • Any radiotherapy within 1 week of starting treatment on protocol.
  • Any major surgery within 2 weeks of starting treatment on protocol.
  • 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: (a) Mean resting corrected QT interval (QTc) > 470 msec where QT interval is corrected for heart rate using Frederica's formula (QTcF) (b) 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. (c) 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 > 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 as defined in protocol

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