18 and older, any sex, with KRAS Gene Mutation or Metastatic Malignant Neoplasm in the Brain. Patients with the condition only — healthy volunteers not accepted.
Results — posted to ClinicalTrials.gov
Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.
Progression Free Survival (PFS)Primary· 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:
* 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
Group
Value
95% CI
Treatment (Regorafenib, Methotrexate)
3.7
1.8 – 8.6
Objective Response Rate (ORR)Secondary· 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.
Group
Value
95% CI
Treatment (Regorafenib, Methotrexate)
16.7
3.5 – 41.4
Disease Control Rate (DCR)Secondary· 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
Group
Value
95% CI
Treatment (Regorafenib, Methotrexate)
66.7
41.0 – 86.7
Number of Participants With Adverse EventsSecondary· Up to 38 months
Participants who experienced any treatment emergent adverse event and any ≥ grade 3 adverse event is reported.
Any grade
Group
Value
95% CI
Treatment (Regorafenib, Methotrexate)
17
≥ grade 3
Group
Value
95% CI
Treatment (Regorafenib, Methotrexate)
14
Trough Serum Concentration of MethotrexateSecondary· 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, Day 1
Group
Value
95% CI
Treatment (Regorafenib, Methotrexate)
0.04
± 0.02
Cycle 1, Day 8
Group
Value
95% CI
Treatment (Regorafenib, Methotrexate)
0.04
± 0.01
Cycle 1, Day 15
Group
Value
95% CI
Treatment (Regorafenib, Methotrexate)
0.05
± 0.03
Cycle 1, Day 22
Group
Value
95% CI
Treatment (Regorafenib, Methotrexate)
0.05
± 0.02
Maximum Serum Concentration (Cmax) of MethotrexateSecondary· 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, Day 1
Group
Value
95% CI
Treatment (Regorafenib, Methotrexate)
0.43
± 0.23
Cycle 1, Day 8
Group
Value
95% CI
Treatment (Regorafenib, Methotrexate)
0.60
± 0.30
Cycle 1, Day 15
Group
Value
95% CI
Treatment (Regorafenib, Methotrexate)
0.60
± 0.43
Adverse events — posted to ClinicalTrials.gov
Time frame: Up to 38 months.
Reporting threshold: 0%.
Adverse-event reports describe events observed during the trial — not all are caused by the drug.
Treatment (Regorafenib, Methotrexate)
Serious: 8/18 (44%)
Deaths: 2/18
Serious adverse events (10 terms)
Reaction
System
Treatment (Regorafenib, Me…
Dyspnea
Respiratory, thoracic and mediastinal disorders
—
Hypoxia
Respiratory, thoracic and mediastinal disorders
—
Aspiration
Respiratory, thoracic and mediastinal disorders
—
Pneumothorax
Respiratory, thoracic and mediastinal disorders
—
Hemoptysis
Respiratory, thoracic and mediastinal disorders
—
Abdominal pain
Gastrointestinal disorders
—
Thromboembolic event: pulmonary embolism
Vascular disorders
—
Atrial fibrillation
Cardiac disorders
—
Pancreatitis
Gastrointestinal disorders
—
Productive Cough
Respiratory, thoracic and mediastinal disorders
—
Other adverse events (123 terms — click to expand)
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.
Publications & conference data
8 peer-reviewed publications reference this trial (live from Europe PMC):
NCT07498465 — A Study to Find the Highest Dose of SNDX-5613 (Revumenib) as a Treatment Option After Hematopoietic Stem Cell Transplant
· Phase 1
· withdrawn
NCT07072585 — Testing the Addition of Daratumumab to Chemotherapy for Treating Patients With Newly-Diagnosed T-Cell Lymphoblastic Leuk
· Phase 2, PHASE3
· not yet recruiting
NCT07321912 — Eflornithine (DFMO) for Ewing Sarcoma and Osteosarcoma
· Phase 2
· not yet recruiting
NCT07446400 — A Trial to Examine the Interaction of Repinatrabit With Ethinyl Estradiol/Norethindrone, Metformin,Carbamazepine, Rosuva
· Phase 1
· recruiting
NCT07477691 — Immune Modulation During Palynziq® Treatment in Adults (IMPALA)
· Phase 4
· not yet recruiting
Other recruiting trials for KRAS Gene Mutation
Currently open trials in the same condition.
NCT03808558 — Phase 2 Study of TVB-2640 in KRAS Non-Small Cell Lung Carcinomas
· Phase 2
· active not recruiting
NCT03087071 — Panitumumab With or Without Trametinib in Treating Patients With Stage IV Colorectal Cancer
· Phase 2
· active not recruiting
NCT03065387 — Neratinib and Everolimus, Palbociclib, or Trametinib in Treating Participants With Refractory and Advanced or Metastatic
· Phase 1
· active not recruiting
NCT02642042 — Trametinib and Docetaxel in Treating Patients With Recurrent or Stage IV KRAS Mutation Positive Non-small Cell Lung Canc
· Phase 2
· active not recruiting
Other Stanford University trials
Trials by the same sponsor.
NCT05945147 — Ketamine and Midazolam Infusions for CRPS: Feasibility Study
· Phase 2
· withdrawn
NCT04225949 — Patients Understanding of PROM Graphs
· NA
· withdrawn
NCT06273098 — School-Based Bladder Health Intervention
· NA
· withdrawn
NCT04652635 — Management of Nailbed Injuries
· NA
· withdrawn
NCT05443503 — Stanford Spine Keeper - Managing Your Low Back Pain
· NA
· suspended
Publications: Europe PMC API search by NCT ID, retrieved 10 June 2026
Drug + disease cross-links: matched in real time against Drug Landscape's normalised drug + company + condition tables
Sponsor: as reported to ClinicalTrials.gov by Stanford University
Last refreshed: 1 August 2023
Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03520842.