Regorafenib and Methotrexate in Treating Participants With Recurrent or Metastatic KRAS Mutated Non-Small Cell Lung Cancer

NCT03520842 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: IRB-43398NCI-2018-00413LUN0097
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well regorafenib works together with methotrexate in treating participants with metastatic non-squamous non-small cell lung cancer with tumors that harbor a KRAS mutation. Regorafenib is a targeted therapy that works on different cancer pathways to stop the growth of tumor cells and stop them from spreading. Methotrexate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving regorafenib and methotrexate together may work in treating participants with KRAS mutated non-small cell lung cancer.

Conditions

KRAS Gene Mutation; Metastatic Malignant Neoplasm in the Brain; Recurrent Non-Small Cell Lung Carcinoma; Stage IV Non-Small Cell Lung Cancer AJCC v7

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  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: * Complete Response (CR) = Disappearance of all target lesions * Partial Response (PR) = ≥ 30% decrease in the sum of the longest diameter of target lesions * Overall Response (OR) = CR + PR * Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions, and/or the appearance of one or more new lesion(s) * Stable disease (SD) = Small changes that do not meet any of the above criteria

  From first study treatment assessed up to 15 months

Secondary Outcomes (5)

• Objective Response Rate (ORR)

  Up to 24 months

• Disease Control Rate (DCR)

  At 8 weeks

• Number of Participants With Adverse Events

  Up to 38 months

• Trough Serum Concentration of Methotrexate

  Cycle 1, Days 1, 8, 15, and 22

• Maximum Serum Concentration (Cmax) of Methotrexate

  Cycle 1, Days 1, 8, and 15

Study Arms (1)

Treatment (regorafenib, methotrexate)

EXPERIMENTAL

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.

Drug: Methotrexate; Other: Pharmacokinetic Study; Drug: Regorafenib

Interventions

Methotrexate DRUG

Given PO

Also known as: Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate, CL 14377, CL-14377, Emtexate, Emthexat, Emthexate, Farmitrexat, Fauldexato, Folex, Folex PFS, Lantarel, Ledertrexate, Lumexon, Maxtrex, Medsatrexate, Metex, Methoblastin, Methotrexate LPF, Methotrexate Methylaminopterin, Methotrexatum, Metotrexato, Metrotex, Mexate, Mexate-AQ, MTX, Novatrex, Rheumatrex, Texate, Tremetex, Trexeron, Trixilem, WR-19039

Treatment (regorafenib, methotrexate)

Pharmacokinetic Study OTHER

Correlative studies

Also known as: PHARMACOKINETIC, PK Study

Treatment (regorafenib, methotrexate)

Regorafenib DRUG

Given PO

Also known as: BAY 73-4506, Stivarga

Treatment (regorafenib, methotrexate)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University School of Medicine

Palo Alto, California, 94304, United States

Location

MeSH Terms

Conditions

Brain Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

Methotrexate; merphos; Pharmacogenomic Variants; regorafenib

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Polymorphism, Genetic; Genetic Variation; Genetic Phenomena

Results Point of Contact

• Title: Heather Wakelee
• Organization: Stanford University

ccto-website@stanford.edu

(650) 498-6000

Study Officials

• Heather Wakelee

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine (Oncology)

Study Record Dates

• First Submitted: April 18, 2018
• First Posted: May 11, 2018
• Study Start: August 14, 2018
• Primary Completion: June 15, 2022
• Study Completion: June 15, 2022
• Last Updated: August 1, 2023
• Results First Posted: August 1, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)