Osimertinib Alone or With Chemotherapy for EGFR-Mutant Lung Cancers

NCT04410796 | Recruiting Phase 2 FDA Drug

• 1 other identifier: 20-011
• Study Type: interventional
• Target: 571
• Locations: 1 country
• Sites: 18

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.

Conditions

Metastatic Non-small Cell Lung Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Determine the progression-free survival

  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.

  2 years

Secondary Outcomes (1)

• overall response rate

  2 years

Study Arms (2)

Osimertinib alone

EXPERIMENTAL

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.

Drug: Osimertinib

Osimertinib plus Carboplatin and Pemetrexed

EXPERIMENTAL

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.

Drug: Osimertinib; Drug: Carboplatin; Drug: Pemetrexed

Interventions

Osimertinib DRUG

80mg orally daily

Osimertinib alone; Osimertinib plus Carboplatin and Pemetrexed

Carboplatin DRUG

Carboplatin (AUC 5 IV q 3 weeks)

Osimertinib plus Carboplatin and Pemetrexed

Pemetrexed DRUG

Pemetrexed (500mg/m2 IV q 3 weeks) for a total of 4 cycles

Osimertinib plus Carboplatin and Pemetrexed

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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.
• Screening for chronic conditions is not required.
• In patients with resolved or chronic hepatitis B infection (inactive carrier state) or active controlled HBV infection on treatment with osimertinib
• Recommend monthly monitoring of ALT/AST, HBV DNA levels and HBsAg (if negative at baseline)
• Where liver signs and symptoms of viral reactivation appear (HBV DNA levels exceeding 10-fold from baseline or ≥100 IU/ml (if baseline HBV DNA levels are undetectable) or conversion of HBsAg negative to positive):
• Expert hepatologist/specialist oversight of the patient is required
• Consider interruption or discontinuation of study treatment, based on riskbenefit assessment

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• AstraZeneca: collaborator
• Guardant Health, Inc.: collaborator

Study Sites (18)

UC Davis Cancer Center (Data Collection Only)

Sacramento, California, 95817, United States

RECRUITING

University of California San Francisco

San Francisco, California, 94143, United States

ACTIVE NOT RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

John Hopkins Medical Center

Baltimore, Maryland, 21287, United States

RECRUITING

Massachusetts General Hospital (Data Collection Only)

Boston, Massachusetts, 02114, United States

RECRUITING

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

RECRUITING

Hackensack Meridian Health

Hackensack, New Jersey, 07601, United States

RECRUITING

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

RECRUITING

Memorial Sloan Kettering Commack (Limited protocol activities)

Commack, New York, 11725, United States

RECRUITING

Memorial Sloan Kettering Westchester (Limited protocol activities)

Harrison, New York, 10604, United States

RECRUITING

New York University

New York, New York, 10010, United States

RECRUITING

Columbia University (Data Collection Only)

New York, New York, 10032, United States

ACTIVE NOT RECRUITING

Memorial Sloan Kettering Cancer Center (All protocol activities)

New York, New York, 10065, United States

RECRUITING

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Uniondale, New York, 11553, United States

RECRUITING

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

RECRUITING

MD ANDERSON CANCER CENTER (Data Collection Only)

Houston, Texas, 77030, United States

RECRUITING

University of Washington (Data Collection Only)

Seattle, Washington, 98109, United States

RECRUITING

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

osimertinib; Carboplatin; Pemetrexed

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Study Officials

• Helena Yu, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Helena Yu, MD

CONTACT

646-608-2252; yuh@mskcc.org

Gregory Riely, MD, PhD

CONTACT

646-608-3913

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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 treatment.

Study Record Dates

• First Submitted: May 28, 2020
• First Posted: June 1, 2020
• Study Start: May 28, 2020
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027
• Last Updated: June 3, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share

Locations

US (18)