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
Overview
- Phase
- Phase 2
- Intervention
- Osimertinib
- Conditions
- Metastatic Non-small Cell Lung Cancer
- Sponsor
- Memorial Sloan Kettering Cancer Center
- Enrollment
- 571
- Locations
- 18
- Primary Endpoint
- Determine the progression-free survival
- Status
- Recruiting
- Last Updated
- 5 months ago
Overview
Brief 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.
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. 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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 , or tumor assessments within +7 days of Osimertinib start, 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)
- •Hemoglobin ≥ 9 g/dL
- •Platelets ≥ 150,000mm\^3 or 150 x 10\^9/L
Exclusion Criteria
- •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 CYP3A
- •All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer effects on CYP3A
- •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.
Arms & Interventions
Osimertinib alone
All patients will receive osimertinib 80mg orally daily. Subjects randomized to Arm A may be dispensed osimertinib for 2 cycles from Cycle 4 onward. Patients will be required to complete a pill diary beginning at Cycle 4.
Intervention: Osimertinib
Osimertinib plus Carboplatin and Pemetrexed
All 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. Patients will be required to complete a pill diary beginning at Cycle 4.
Intervention: Osimertinib
Osimertinib plus Carboplatin and Pemetrexed
All 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. Patients will be required to complete a pill diary beginning at Cycle 4.
Intervention: Carboplatin
Osimertinib plus Carboplatin and Pemetrexed
All 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. Patients will be required to complete a pill diary beginning at Cycle 4.
Intervention: Pemetrexed
Outcomes
Primary Outcomes
Determine the progression-free survival
Time Frame: 2 years
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 Outcomes
- overall response rate(2 years)