- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03520842
Regorafenib and Methotrexate in Treating Participants With Recurrent or Metastatic KRAS Mutated Non-Small Cell Lung Cancer
Study of Regorafenib in Combination With Oral Methotrexate for KRAS Mutated Non-Small Cell Lung Cancer (NSCLC)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVES:
I. To determine the progression free survival (PFS) of the combination of regorafenib and methotrexate for metastatic KRAS mutated non-small cell lung cancer (NSCLC) patients who have received at least 1 prior systemic therapy.
SECONDARY OBJECTIVES:
I. To determine the objective response rate (ORR) of the combination of regorafenib and methotrexate for metastatic KRAS mutated NSCLC patients who have received at least 1 prior systemic therapy.
II. To determine the disease control rate (DCR) at 8 weeks of the combination of regorafenib and methotrexate for metastatic KRAS mutated NSCLC patients who have received at least 1 prior systemic therapy.
III. To determine the safety of the combination of regorafenib and methotrexate in metastatic KRAS mutated NSCLC patients who have received at least 1 prior systemic therapy, assessed as the number of subjects that experience a treatment-emergent adverse event.
IV. To determine the safety of the combination of regorafenib and methotrexate in metastatic KRAS-mutated NSCLC patients who have received at least 1 prior systemic therapy, assessed as the number (percent) of participants experiencing any dose-limiting toxicity (DLT).
V. To determine the pharmacokinetic parameters of methotrexate when combined with regorafenib (i.e., trough and maximum serum concentration [Cmax]).
OUTLINE:
Participants receive regorafenib orally (PO) once daily (QD) and methotrexate PO twice weekly with 2-3 days apart on a 3 week on / 1 week off schedule. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, participants will come in for an end of study treatment visit.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
California
-
Palo Alto, California, United States, 94304
- Stanford University School of Medicine
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Histologic or cytologic confirmed diagnosis of non-squamous non-small cell lung cancer that is recurrent or metastatic.
- Documentation of pathogenic KRAS mutation
- Previous receipt of at least one systemic therapy for recurrent or metastatic disease OR previous receipt of adjuvant systemic therapy within 6 months of enrollment; there is no limit on number of prior therapies allowed
- Prior systemic therapy must be completed within 2 weeks of study treatment, with either improvement of clinically significant treatment-related toxicities to grade 0-1 OR stabilized to a new baseline
- Previously treated OR asymptomatic non-progressing < 1 cm untreated brain metastases are allowed
- Measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria
- Ability to understand and the willingness to sign a written informed consent document
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Absolute neutrophil count (ANC) ≥ 1500/mm^3
- Platelet count ≥ 100,000 /mm^3
- Hemoglobin (Hb) ≥ 9 g/dL
- Serum creatinine ≤ 1.5x upper limit of normal (ULN) OR calculated (Cockcroft Gault formula) or measured creatinine clearance ≥ 50 mL/min for patients with creatinine levels > 1.5x ULN
- Total bilirubin ≤ 1.5x ULN OR direct bilirubin ≤ ULN for patients with total bilirubin levels > 1.5x ULN
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3x ULN (≤ 5x ULN for patients with liver involvement of their cancer)
- Must be able to swallow and retain oral medication
- Women patients of childbearing potential and men patients with women partners of childbearing potential must agree to use adequate contraception or agree to abstain from heterosexual activity beginning at the time of signing informed consent until at least 3 months after the last dose of study treatment; post-menopausal women (defined as no menses for at least 1 year) and surgically sterilized women are not considered childbearing
Exclusion Criteria:
- Previously treated with regorafenib
- Known allergy to regorafenib or methotrexate
- Currently receiving another systemic standard or investigational anti-cancer therapy; prior investigational therapy must be completed within 4 half-lives (if known) or 2 weeks, whichever is longer; the maximal washout of investigational therapy will not exceed 4 weeks prior to study treatment; bone medications such as bisphosphonates and receptor activator of nuclear factor kappa-Β (RANK) ligand inhibitors permitted
- Leptomeningeal disease as documented by cerebrospinal fluid (CSF) cytology
Clinically significant cardiovascular related disease including:
- Uncontrolled hypertension (systolic pressure > 140 mm Hg or diastolic pressure > 90 mmHg on repeated measurements, i.e., 3 or more separate days within one week) despite optimal medical management
- Congestive heart failure - New York Heart Association (NYHA) class III or greater
- Active coronary artery disease (i.e., unstable or new onset angina within 3 months of study treatment; myocardial infarction within 6 months of study treatment)
- Clinically significant cardiac arrhythmias other than atrial flutter/fibrillation
- Stroke, including transient ischemic attacks, within 6 months of study treatment
- Other clinically significant arterial events, except for controlled asymptomatic pulmonary embolism, within 6 months of study treatment
- Clinically significant hemorrhage or bleeding event within 1 month of study treatment
- Uncontrolled symptomatic pleural effusion or ascites
- Known active additional malignancy that is undergoing or expected to undergo systemic treatment during duration of study participation
- Known history of human immunodeficiency virus (HIV) infection or known current active hepatitis B (i.e., hepatitis [Hep] B deoxyribonucleic acid [DNA] positive in prior 3 months) or hepatitis C infection (i.e., Hep C ribonucleic acid [RNA] positive in prior 3 months)
- Major surgical procedure (e.g., involving the opening of a major body cavity) within 4 weeks of study treatment; this does not apply to low risk procedures (i.e., thoracentesis; paracentesis; chest tube / PleurX catheter placement; line placement; needle biopsy of tumor; and bronchoscopy)
- Presence of a clinically significant non-healing wound, non-healing ulcer, or bone fracture
Concomitant therapy required at time of first dose of study treatment, including:
- Strong CYP3A4 inhibitors and CYP3A4 inducers
- Regular use of nonsteroidal anti-inflammatory drugs (NSAIDs), proton pump inhibitors, and probenecid
- Women who are pregnant or breast feeding
- Any condition which, in the investigator's opinion, including substance abuse, medical, psychological or social conditions that makes the patient unsuitable for trial participation or may interfere with the patient's participation in the study
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (regorafenib, methotrexate)
Participants receive regorafenib PO QD on days 1-21, and methotrexate PO twice weekly with 2-3 days apart on a 3 week on/ 1 week off cycle.
Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
|
Correlative studies
Other Names:
Given PO
Other Names:
Given PO
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression Free Survival (PFS)
Time Frame: From first study treatment assessed up to 15 months
|
Progression free survival (PFS), measured from time of first study treatment until objective tumor progression as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria or death from any cause, whichever occurs earlier. PFS was calculated using the Kaplan-Meier method along with 95% confidence interval. RECIST v1.1 criteria are:
|
From first study treatment assessed up to 15 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective Response Rate (ORR)
Time Frame: Up to 24 months
|
Objective response rate (ORR; as determined by RECIST v1.1) will be assessed as the proportion (percent) of participants with either complete response (CR; disappearance of all target lesions) or partial response (PR; ≥ 30% decrease in the sum of the longest diameter of target lesions), with exact 95% confidence intervals based on a binomial distribution.
|
Up to 24 months
|
Disease Control Rate (DCR)
Time Frame: At 8 weeks
|
Disease control rate (DCR) will be assessed as the proportion of complete responses (CR) + partial responses (PR) + stable disease (SD) after 8 weeks of treatment (+/- 1 week), as determined by using RECIST v1.1
|
At 8 weeks
|
Number of Participants With Adverse Events
Time Frame: Up to 38 months
|
Participants who experienced any treatment emergent adverse event and any ≥ grade 3 adverse event is reported.
|
Up to 38 months
|
Trough Serum Concentration of Methotrexate
Time Frame: Cycle 1, Days 1, 8, 15, and 22
|
Pharmacokinetics (PK) of methotrexate when co-administered with regorafenib, as indicated by the trough serum concentration, was accessed by a fluorescent polarization immunoassay, and is reported as the mean with standard deviation.
Participants treated with at least 1 dose of regorafenib and methotrexate and with at least one evaluable baseline pharmacokinetic sample and one follow up trough pharmacokinetic sample treated were included.
|
Cycle 1, Days 1, 8, 15, and 22
|
Maximum Serum Concentration (Cmax) of Methotrexate
Time Frame: Cycle 1, Days 1, 8, and 15
|
Pharmacokinetics (PK) of methotrexate when co-administered with regorafenib, as indicated by the maximum serum concentration (Cmax) of methotrexate, was assessed by a fluorescent polarization immunoassay, and is reported as the mean with standard deviation.
Participants treated with at least 1 dose of regorafenib and methotrexate and with at least one evaluable Cmax pharmacokinetic sample were included in the assessment.
|
Cycle 1, Days 1, 8, and 15
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Heather Wakelee, Stanford University
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Lung Diseases
- Neoplasms by Site
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Neoplasms
- Lung Neoplasms
- Carcinoma, Non-Small-Cell Lung
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Dermatologic Agents
- Reproductive Control Agents
- Abortifacient Agents, Nonsteroidal
- Abortifacient Agents
- Folic Acid Antagonists
- Methotrexate
Other Study ID Numbers
- IRB-43398
- NCI-2018-00413 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- LUN0097 (Other Identifier: OnCore)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Recurrent Non-Small Cell Lung Carcinoma
-
National Cancer Institute (NCI)CompletedStage IIIA Non-small Cell Lung Cancer | Stage IIIB Non-small Cell Lung Cancer | Extensive Stage Small Cell Lung Cancer | Recurrent Small Cell Lung Cancer | Recurrent Non-small Cell Lung Cancer | Stage IV Non-small Cell Lung CancerUnited States
-
Mayo ClinicNational Cancer Institute (NCI)CompletedStage IIIA Non-Small Cell Lung Cancer | Stage IIIB Non-Small Cell Lung Cancer | Lung Adenocarcinoma | Recurrent Non-Small Cell Lung Carcinoma | Stage IV Non-Small Cell Lung Cancer | Extensive Stage Small Cell Lung Carcinoma | Squamous Cell Lung Carcinoma | Recurrent Small Cell Lung CarcinomaUnited States
-
National Cancer Institute (NCI)CompletedStage IIIA Non-Small Cell Lung Cancer | Recurrent Non-Small Cell Lung Carcinoma | Stage IV Non-Small Cell Lung Cancer | Stage IIA Non-Small Cell Lung Carcinoma | Stage IIB Non-Small Cell Lung Carcinoma | Stage IB Non-Small Cell Lung CarcinomaUnited States
-
Vanderbilt-Ingram Cancer CenterWithdrawnRecurrent Non-Small Cell Lung Carcinoma | Stage IV Non-Small Cell Lung Cancer
-
National Cancer Institute (NCI)CompletedStage IIIA Non-Small Cell Lung Cancer | Stage IIIB Non-Small Cell Lung Cancer | Recurrent Non-Small Cell Lung Carcinoma | Stage IV Non-Small Cell Lung CancerUnited States
-
Wake Forest University Health SciencesNational Cancer Institute (NCI)CompletedStage IIIB Non-Small Cell Lung Cancer | Recurrent Non-Small Cell Lung Carcinoma | Stage IV Non-Small Cell Lung CancerUnited States
-
University of Wisconsin, MadisonNational Cancer Institute (NCI)CompletedStage IIIA Non-small Cell Lung Cancer | Stage IIIB Non-small Cell Lung Cancer | Extensive Stage Small Cell Lung Cancer | Recurrent Small Cell Lung Cancer | Recurrent Non-small Cell Lung Cancer | Stage IV Non-small Cell Lung Cancer | Healthy, no Evidence of Disease | Limited Stage Small Cell Lung... and other conditionsUnited States
-
Bristol-Myers SquibbActive, not recruitingNon-small Cell Lung Cancer | Recurrent Non-small Cell Lung Cancer | Metastatic Non-small Cell Lung CancerAustralia, Russian Federation, United States, Argentina, Austria, Belgium, Brazil, Chile, France, Germany, Ireland, Italy, Mexico, Netherlands, Poland, Romania, Spain, Switzerland, United Kingdom
-
Rutgers, The State University of New JerseyNational Cancer Institute (NCI); Rutgers Cancer Institute of New JerseyCompletedNon-small Cell Lung Cancer | Advanced Non-small Cell Lung Cancer | Recurrent Non-small Cell Lung CancerUnited States
-
Luye Pharma Group Ltd.UnknownNon Small Cell Lung Cancer | Non Small Cell Lung Cancer Metastatic | Non Small Cell Lung Cancer RecurrentChina
Clinical Trials on Pharmacokinetic Study
-
M.D. Anderson Cancer CenterCompletedMetastatic Carcinoma in the Adrenal Cortex | Stage III Adrenal Cortex Carcinoma AJCC v8 | Stage IV Adrenal Cortex Carcinoma AJCC v8 | Unresectable Adrenal Cortex CarcinomaUnited States
-
OHSU Knight Cancer InstituteOregon Health and Science University; Janssen, LP; The Leukemia and Lymphoma...TerminatedRecurrent Acute Myeloid Leukemia | Refractory Acute Myeloid LeukemiaUnited States
-
National Cancer Institute (NCI)Active, not recruitingAdvanced Malignant Solid Neoplasm | Refractory Malignant Solid Neoplasm | Recurrent Ewing Sarcoma | Recurrent Hepatoblastoma | Recurrent Histiocytic and Dendritic Cell Neoplasm | Recurrent Langerhans Cell Histiocytosis | Recurrent Malignant Germ Cell Tumor | Recurrent Malignant Solid Neoplasm | Recurrent... and other conditionsUnited States, Puerto Rico
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)CompletedAnatomic Stage III Breast Cancer AJCC v8 | Anatomic Stage IIIA Breast Cancer AJCC v8 | Anatomic Stage IIIB Breast Cancer AJCC v8 | Anatomic Stage IIIC Breast Cancer AJCC v8 | Prognostic Stage III Breast Cancer AJCC v8 | Prognostic Stage IIIA Breast Cancer AJCC v8 | Prognostic Stage IIIB Breast... and other conditionsUnited States
-
University of Southern CaliforniaNational Cancer Institute (NCI)WithdrawnRecurrent Bladder Carcinoma | Bladder Cancer Stage 0 | Bladder Cancer Stage IUnited States
-
Seoul National University HospitalCompleted
-
Chiang Mai UniversityThailand Research FundUnknownPharmacokinetics | Efavirenz | PenicilliosisThailand
-
Rabin Medical CenterCompletedCongenital Cytomegalovirus InfectionIsrael
-
ISA PharmaceuticalsRegeneron PharmaceuticalsActive, not recruitingSquamous Cell Carcinoma of the Oropharynx | HPV16 PositiveNetherlands, United States, United Kingdom, France, Belgium, Czechia, Spain, Italy, Germany, Brazil, Hungary, Mexico, Poland
-
City of Hope Medical CenterNational Cancer Institute (NCI)Active, not recruitingRecurrent Mantle Cell Lymphoma | Recurrent Marginal Zone Lymphoma | Recurrent Small Lymphocytic Lymphoma | Recurrent Diffuse Large B-Cell Lymphoma | Refractory Diffuse Large B-Cell Lymphoma | Refractory Chronic Lymphocytic Leukemia | Recurrent Non-Hodgkin Lymphoma | Refractory Non-Hodgkin Lymphoma | Richter Syndrome and other conditionsUnited States