Clinical Trials /

Osimertinib Alone or With Chemotherapy for EGFR-Mutant Lung Cancers

NCT04410796

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Osimertinib Alone or With Chemotherapy for EGFR-Mutant Lung Cancers
  • Official Title: A Phase 2 Randomized Study of Osimertinib Versus Osimertinib Plus Chemotherapy for Patients With Metastatic EGFR-Mutant Lung Cancers That Have Detectable EGFR-Mutant cfDNA in Plasma After Initiation of Osimertinib

Clinical Trial IDs

  • ORG STUDY ID: 20-011
  • NCT ID: NCT04410796

Conditions

  • Metastatic Non-small Cell Lung Cancer

Interventions

DrugSynonymsArms
OsimertinibOsimertinib alone
CarboplatinOsimertinib plus Carboplatin and Pemetrexed
PemetrexedOsimertinib plus Carboplatin and Pemetrexed

Purpose

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.

Detailed 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.

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Osimertinib aloneExperimentalAll patients will receive osimertinib 80mg orally daily.
  • Osimertinib
Osimertinib plus Carboplatin and PemetrexedExperimentalAll patients will receive osimertinib 80mg orally daily. Patients receive Carboplatin (AUC 5 IV q 3 weeks) and Pemetrexed (500mg/m2 IV q 3 weeks) for a total of 4 cycles followed by pemetrexed maintenance from cycle 8 onwards.
  • Osimertinib
  • Carboplatin
  • Pemetrexed

Eligibility 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 or cfDNA, confirmed
             at enrolling institution

          -  No prior EGFR TKI therapy and 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

          -  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)

               -  Hemoglobin ≥ 9 g/dL

               -  Platelets ≥ 150,000mm^3 or 150 x 10^9/L

               -  AST, ALT ≤ 2.5 x ULN with no liver metastases or < 5x ULN with the presence of
                  liver metastases

               -  Total bilirubin ≤ 1.5 x ULN if no liver metastases or < 3 x ULN in the presence
                  of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver
                  metastases

               -  Absolute neutrophil count (ANC) ≥ 1500 cells/mm^3

               -  Creatinine clearance ≥ 60 mL/min calculated by Cockcroft and Gault equation

          -  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:

               -  Female subjects should be using highly effective contraceptive measures, and must
                  have a negative pregnancy test and not be breast-feeding prior to start of dosing
                  if of child-bearing potential 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 sterilization by hysterectomy, bilateral
                  oophorectomy or bilateral salpingectomy but not tubal ligation

               -  Male subjects should be willing to use barrier contraception

        Exclusion Criteria: Initial

          -  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:

               -  Mean resting corrected QT interval (QTc) > 470 msec

               -  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

          -  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

               -  Hemoglobin ≥ 9 g/dL

               -  Platelets ≥ 100,000mm^3 or 100 x 10^9/L

               -  Creatinine clearance ≥ 60ml/min

               -  AST, ALT ≤ 3x ULN with no liver metastases or ≤ 5x ULN with the presence of liver
                  metastases

               -  Total bilirubin ≤ 1.5 x ULN if no liver metastases or ≤ 3 x ULN in the presence
                  of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver
                  metastases

               -  Absolute neutrophil count (ANC) ≥ 1500 cells/mm3Must have at least stable disease
                  per RECIST 1.1 assessment prior to initiating chemotherapy at C4D1

               -  Eligibility testing (KPS, bloodwork) should be tested at C3D1. If the subject's
                  evaluation does not meet eligibility criteria, any result obtained between C3 and
                  C4 can be used

        Please note: All 'Initial' Exclusion Criteria must be re-confirmed prior to randomization.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Determine the progression-free survival
Time Frame:2 years
Safety Issue:
Description:As the primary endpoint for the treatment comparison, it is the duration of time from randomization to the time of disease progression (in the CNS or systemically) or death. In addition, as a secondary endpoint, PFS is measured from the start of treatment to disease progression or death. Intracranial progression-free survival (PFS) is defined as the duration of time from time of randomization to time of progression (in the CNS) or death, whichever occurs first. Overall survival (OS) is defined as the duration of time from first treatment to time of death.

Secondary Outcome Measures

Measure:overall response rate
Time Frame:2 years
Safety Issue:
Description:Best overall response rate (confirmed partial and complete responses) will be assessed as part of this study. All responses must be confirmed on subsequent scan to be considered a true response. Tumor response will be assessed using RECIST 1.1

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • EGFR-Mutant Lung Cancers
  • Osimertinib
  • Osimertinib Plus Chemotherapy
  • 20-011

Last Updated

May 28, 2020