Lung Cancer Clinical Trial

Osimertinib Alone or With Chemotherapy for EGFR-Mutant Lung Cancers

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.

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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.

View Eligibility Criteria

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/ 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)

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 ≤ ULN OR calculated creatinine clearance ≥ 60ml/min calculated by Cockcroft and Gault equation
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 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:

Mean resting corrected QT interval (QTc) > 470 msec where QT interval is corrected for heart rate using Frederica's formula (QTcF).
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 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 ≤ ULN OR calculated 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.

Study is for people with:

Lung Cancer

Phase:

Phase 2

Estimated Enrollment:

571

Study ID:

NCT04410796

Recruitment Status:

Recruiting

Sponsor:

Memorial Sloan Kettering Cancer Center

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There are 16 Locations for this study

See Locations Near You

UC Davis Cancer Center (Data Collection Only)
Sacramento California, 95817, United States More Info
Jonathan Riess, MD
Contact
916-734-5959
University of California San Francisco
San Francisco California, 94143, United States More Info
Collin Blakely, MD
Contact
415-885-3882
Moffitt Cancer Center
Tampa Florida, 33612, United States More Info
Bruna Pellini, MD
Contact
888-663-3488
John Hopkins Medical Center
Baltimore Maryland, 21287, United States
Massachusetts General Hospital (Data Collection Only)
Boston Massachusetts, 02114, United States More Info
Susan Himes, PhD
Contact
617-726-2000
Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
Basking Ridge New Jersey, 07920, United States More Info
Helen Yu, MD
Contact
646-608-2252
Hackensack Meridian Health
Hackensack New Jersey, 07601, United States More Info
Kaushal Parikh, MD
Contact
551-996-5087
Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
Middletown New Jersey, 07748, United States More Info
Helena Yu, MD
Contact
646-608-2252
Memorial Sloan Kettering Bergen (Limited Protocol Activities)
Montvale New Jersey, 07645, United States More Info
Helena Yu, MD
Contact
646-608-2252
Memorial Sloan Kettering Commack (Limited protocol activities)
Commack New York, 11725, United States More Info
Helena Yu, MD
Contact
646-608-2252
Memorial Sloan Kettering Westchester (Limited protocol activities)
Harrison New York, 10604, United States More Info
Helena Yu, MD
Contact
646-608-2252
New York University
New York New York, 10010, United States More Info
Joshua Sabari, MD
Contact
212-731-5662
Columbia University (Data Collection Only)
New York New York, 10032, United States More Info
Catherine Shu, MD
Contact
212-305-5098
Memorial Sloan Kettering Cancer Center (All protocol activities)
New York New York, 10065, United States More Info
Helena Yu, MD
Contact
646-608-2252
Gregory Riely, MD, PhD
Contact
646-608-3913
Helena Yu, MD
Principal Investigator
Memorial Sloan Kettering Nassau (Limited Protocol Activities)
Uniondale New York, 11553, United States More Info
Helena Yu, MD
Contact
646-608-2252
Sarah Cannon Research Institute
Nashville Tennessee, 37203, United States More Info
Melissa Johnson, MD
Contact
615-329-7274

How clear is this clinincal trial information?

Study is for people with:

Lung Cancer

Phase:

Phase 2

Estimated Enrollment:

571

Study ID:

NCT04410796

Recruitment Status:

Recruiting

Sponsor:


Memorial Sloan Kettering Cancer Center

How clear is this clinincal trial information?

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