This phase II Expanded Lung-MAP treatment trial tests tepotinib with or without ramucirumab for the treatment of patients with advanced non-small cell lung cancer that has spread from where it first started (primary site) to other places in the body (stage IV) or that has come back after a period of improvement (recurrent). Tepotinib is used in patients whose cancer has a mutated (changed) form of a gene called MET. It is in a class of medications called kinase inhibitors. It works by blocking the action of the abnormal MET protein that signals tumor cells to multiply. This helps slow or stop the spread of tumor cells. Ramucirumab is a monoclonal antibody that may prevent the growth of new blood vessels that tumors need to grow. Giving tepotinib with ramucirumab may lower the chance of the cancer from growing or spreading in patients with stage IV or recurrent non-small cell lung cancer.
PRIMARY OBJECTIVE: I. To compare the response rate (confirmed or unconfirmed, complete or partial) between participants with MET exon 14 skipping positive non-small cell lung cancer (NSCLC) randomized to tepotinib with or without ramucirumab. SECONDARY OBJECTIVES: I. To compare the frequency of all-grade treatment- related peripheral edema as defined by Common Terminology Criteria for Adverse Events (CTCAE) between the arms. II. To evaluate the frequency and severity of toxicities within each arm. III. To compare progression-free survival between the arms. IV. To compare overall survival between the arms. V. To estimate the duration of response (DoR) among responders within each arm. TRANSLATIONAL MEDICINE OBJECTIVE: I. To establish a tissue/blood repository for participants with MET exon 14 skipping non-small cell lung cancer (NSCLC). OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive ramucirumab intravenously (IV) over 30-60 minutes on day 1 of each cycle and tepotinib orally (PO) once daily (QD) on days 1-21 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive tepotinib PO QD on days 1-21 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients optionally undergo lymphoscintigraphy scan at screening prior to treatment, at the first occurrence of peripheral edema (defined as the development of grade ≥ 1 CTCAE Edema Limbs affecting either the arms, hands, or legs), and if peripheral edema increases in attribution. Patients also undergo blood collection, computed tomography (CT) scan and/or magnetic resonance imaging (MRI) throughout the trial. Additionally, patients undergo urine collection during screening and on study. After completion of study treatment, patients are followed-up every 12 weeks or more often as clinically indicated until progression and then every 6 months for 2 years and at the end of 3 years from date of sub-study randomization.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
56
Undergo blood and urine sample collection
Undergo CT scan
Undergo lymphoscintigraphy scan
Undergo MRI
Given IV
Given PO
Gulf Health Hospitals Inc/Infirmary Cancer Care - Malbis
Daphne, Alabama, United States
RECRUITINGThomas Hospital
Fairhope, Alabama, United States
RECRUITINGMobile Infirmary Medical Center
Mobile, Alabama, United States
RECRUITINGGulf Health Hospitals Inc/Infirmary Cancer Care - Saraland
Saraland, Alabama, United States
Response rate
Rates will be compared using a chi-squared test at the 1-sided 10% level and also presented as the difference in response rates with the associated 80% confidence interval for the difference, Further, response rates and associated 80% confidence interval will be estimated for each arm.
Time frame: Up to 3 years from date of sub-study randomization
Incidence of treatment-related peripheral edema
The frequency of peripheral edema will be compared using a 2-sided 10% level test of proportions. All-grade peripheral edema will be estimated along with 90% confidence intervals. Data from lymphoscintigraphy imaging will be summarized for baseline and among those with peripheral edema.
Time frame: Up to 3 years from date of sub-study randomization
Incidence and severity of toxicities
Toxicities combining the treatment arms and within each treatment arm will be reported.
Time frame: Up to 3 years from date of sub-study randomization
Progression-free survival
Will be estimated using the method of Kaplan-Meier. Will be compared between the arms using a 1-sided 10% level log-rank test. Medians and associated 80% confidence intervals will be estimated using the Brookmeyer-Crowley method.
Time frame: From date of sub-study randomization to date of first documentation of progression or death due to any cause, assessed up to 3 years
Overall survival
Will be estimated using the method of Kaplan-Meier. Medians and associated 80% confidence intervals will be estimated using the Brookmeyer-Crowley method.
Time frame: Up to 3 years from date of sub-study randomization
Duration of response
Will be estimated using the method of Kaplan-Meier. Medians and associated 80% confidence intervals will be estimated using the Brookmeyer-Crowley method.
Time frame: From date of first documentation of response (complete response [CR] or partial response [PR]) to date of first documentation of progression or death due to any cause among participants who achieve a response (CR or PR), assessed up to 3 years
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro
Jonesboro, Arkansas, United States
RECRUITINGUniversity of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
RECRUITINGKaiser Permanente-Anaheim
Anaheim, California, United States
ACTIVE_NOT_RECRUITINGSutter Auburn Faith Hospital
Auburn, California, United States
RECRUITINGKaiser Permanente-Baldwin Park
Baldwin Park, California, United States
ACTIVE_NOT_RECRUITINGKaiser Permanente-Bellflower
Bellflower, California, United States
ACTIVE_NOT_RECRUITING...and 257 more locations