Last reviewed · How we verify

NCT02168777

Refametinib (BAY86-9766) in Combination With Regorafenib (Stivarga, BAY73-4506) in Patients With Advanced or Metastatic Cancer

Terminated Phase 1 Results posted Last updated 26 January 2018
What this trial tests

Phase 1 trial testing Refametinib (BAY86-9766) in Neoplasms in 20 participants. Terminated before completion.

Timeline
23 June 2014
Primary endpoint
23 October 2015
5 April 2016

Quick facts

Lead sponsorBayer
PhasePhase 1
StatusTerminated
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment20
Start date23 June 2014
Primary completion23 October 2015
Estimated completion5 April 2016
Sites5 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Bayer — full company profile →

Who can join

18 and older, any sex, with Neoplasms. 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.

Maximum Drug Concentration in Plasma After Multiple Dose (Cmax,md) for Refametinib Primary · Cycle 1 Day 21 at 0 (pre-dose), 0.5, 1, 2, 4, 8 and 12 hours post-dose

Maximum drug concentration in plasma after multiple dose for Refametinib. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.

GroupValue95% CI
Ph1b-Refametinib/Regorafenib Cohort 0NA± NA
Ph1b-Refametinib/Regorafenib Cohort -1315.9± 43
Ph1b-Refametinib/Regorafenib Cohort -1a390.7± 52
Maximum Drug Concentration in Plasma After Multiple Dose (Cmax,md) for Refametinib Metabolite M-11 Primary · Cycle 1 Day 21 at 0 (pre-dose), 0.5, 1, 2, 4, 8 and 12 hours post-dose

Maximum drug concentration in plasma after multiple dose for Refametinib metabolite M-11. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.

GroupValue95% CI
Ph1b-Refametinib/Regorafenib Cohort 0NA± NA
Ph1b-Refametinib/Regorafenib Cohort -1104.9± 36
Ph1b-Refametinib/Regorafenib Cohort -1a112.3± 44
Area Under the Plasma Concentration-time Curve From 0 to 12 h After Multiple Dose (AUC(0-12)md) for Refametinib Primary · Cycle 1 Day 21 at 0 (pre-dose), 0.5, 1, 2, 4, 8 and 12 hours post-dose

Area under the plasma concentration-time curve from 0 to 12 h after multiple dose for Refametinib. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.

GroupValue95% CI
Ph1b-Refametinib/Regorafenib Cohort 0NA± NA
Ph1b-Refametinib/Regorafenib Cohort -12399.2± 65
Ph1b-Refametinib/Regorafenib Cohort -1a3632.3± 51
Area Under the Plasma Concentration-time Curve From 0 to 12 h After Multiple Dose (AUC(0-12)md) for Refametinib Metabolite M-11 Primary · Cycle 1 Day 21 at 0 (pre-dose), 0.5, 1, 2, 4, 8 and 12 hours post-dose

Area under the plasma concentration-time curve from 0 to 12 h after multiple dose for Refametinib metabolite M-11. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.

GroupValue95% CI
Ph1b-Refametinib/Regorafenib Cohort 0NA± NA
Ph1b-Refametinib/Regorafenib Cohort -11013.4± 40
Ph1b-Refametinib/Regorafenib Cohort -1a1144.7± 39
Maximum Drug Concentration in Plasma After Multiple Dose (Cmax,md) for Regorafenib Primary · Cycle 1 Day 21 at 0 (pre-dose), 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

Maximum drug concentration in plasma after multiple dose for Regorafenib. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.

GroupValue95% CI
Ph1b-Refametinib/Regorafenib Cohort 0NA± NA
Ph1b-Refametinib/Regorafenib Cohort -11966.0± 17
Ph1b-Refametinib/Regorafenib Cohort -1a2206.4± 34
Maximum Drug Concentration in Plasma After Multiple Dose (Cmax,md) for Regorafenib Metabolite M-2 Primary · Cycle 1 Day 21 at 0 (pre-dose), 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

Maximum drug concentration in plasma after multiple dose for Regorafenib metabolite M-2. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.

GroupValue95% CI
Ph1b-Refametinib/Regorafenib Cohort 0NA± NA
Ph1b-Refametinib/Regorafenib Cohort -11409.1± 20
Ph1b-Refametinib/Regorafenib Cohort -1a1642.7± 98
Maximum Drug Concentration in Plasma After Multiple Dose (Cmax,md) for Regorafenib Metabolite M-5 Primary · Cycle 1 Day 21 at 0 (pre-dose), 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

Maximum drug concentration in plasma after multiple dose for Regorafenib metabolite M-5. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.

GroupValue95% CI
Ph1b-Refametinib/Regorafenib Cohort 0NA± NA
Ph1b-Refametinib/Regorafenib Cohort -11148.8± 90
Ph1b-Refametinib/Regorafenib Cohort -1a1485.7± 255
Area Under the Plasma Concentration-time Curve From 0 to 24 h After Multiple Dose (AUC(0-24)md) for Regorafenib Primary · Cycle 1 Day 21 at 0 (pre-dose), 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

Area under the plasma concentration-time curve from 0 to 24 h after multiple dose for Regorafenib. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.

GroupValue95% CI
Ph1b-Refametinib/Regorafenib Cohort 0NA± NA
Ph1b-Refametinib/Regorafenib Cohort -132359.4± 32
Ph1b-Refametinib/Regorafenib Cohort -1a34352.2± 38
Area Under the Plasma Concentration-time Curve From 0 to 24 h After Multiple Dose (AUC(0-24)md) for Regorafenib Metabolite M-2 Primary · Cycle 1 Day 21 at 0 (pre-dose), 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

Area under the plasma concentration-time curve from 0 to 24 h after multiple dose for Regorafenib metabolite M-2. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.

GroupValue95% CI
Ph1b-Refametinib/Regorafenib Cohort 0NA± NA
Ph1b-Refametinib/Regorafenib Cohort -124139.7± 34
Ph1b-Refametinib/Regorafenib Cohort -1a25826.2± 100
Area Under the Plasma Concentration-time Curve From 0 to 24 h After Multiple Dose (AUC(0-24)md) for Regorafenib Metabolite M-5 Primary · Cycle 1 Day 21 at 0 (pre-dose), 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

Area under the plasma concentration-time curve from 0 to 24 h after multiple dose for Regorafenib metabolite M-5. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.

GroupValue95% CI
Ph1b-Refametinib/Regorafenib Cohort 0NA± NA
Ph1b-Refametinib/Regorafenib Cohort -120531.8± 106
Ph1b-Refametinib/Regorafenib Cohort -1a24029.3± 265
Maximum Drug Concentration in Plasma After Single (First) Dose (Cmax) for Refametinib and Its Metabolite M-11 Secondary · Cycle 1 Day 1 at 0 (pre-dose), 0.5, 1, 2, 4 and 8 hours post-dose

Maximum drug concentration in plasma after single (first) dose for Refametinib and its metabolite M-11. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.

Refametinib
GroupValue95% CI
Ph1b-Refametinib/Regorafenib Cohort 0549.7± 58
Ph1b-Refametinib/Regorafenib Cohort -1273.3± 82
Ph1b-Refametinib/Regorafenib Cohort -1a253.0± 38
Metabolite M-11
GroupValue95% CI
Ph1b-Refametinib/Regorafenib Cohort 058.7± 10
Ph1b-Refametinib/Regorafenib Cohort -137.0± 83
Ph1b-Refametinib/Regorafenib Cohort -1a35.7± 42
Time to Reach Maximum Drug Concentration in Plasma After Single (First) Dose (Tmax) for Refametinib and Its Metabolite M-11 Secondary · Cycle 1 Day 1 at 0 (pre-dose), 0.5, 1, 2, 4 and 8 hours post-dose

Time to reach maximum drug concentration in plasma after single (first) dose for Refametinib and its metabolite M-11. Median and full range were reported.

Refametinib
GroupValue95% CI
Ph1b-Refametinib/Regorafenib Cohort 02.51.00 – 4.02
Ph1b-Refametinib/Regorafenib Cohort -11.00.77 – 7.50
Ph1b-Refametinib/Regorafenib Cohort -1a4.00.97 – 8.00
Metabolite M-11
GroupValue95% CI
Ph1b-Refametinib/Regorafenib Cohort 06.04.02 – 8.00
Ph1b-Refametinib/Regorafenib Cohort -14.01.80 – 7.50
Ph1b-Refametinib/Regorafenib Cohort -1a4.01.93 – 8.00

Adverse events — posted to ClinicalTrials.gov

Time frame: From the start of study treatment until 30 days after last dose of study drug treatment.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Ph1b - Refametinib/Regorafenib Cohort 0
Serious: 0/2 (0%)
Deaths:
Ph1b - Refametinib/Regorafenib Cohort -1
Serious: 4/7 (57%)
Deaths:
Ph1b - Refametinib/Regorafenib Cohort -1a
Serious: 5/11 (45%)
Deaths:

Serious adverse events (12 terms)

ReactionSystemPh1b - Refametinib/Regoraf…Ph1b - Refametinib/Regoraf…Ph1b - Refametinib/Regoraf…
Blood creatine phosphokinase increasedInvestigations
CholangitisHepatobiliary disorders
Urinary tract infectionInfections and infestations
Wound infectionInfections and infestations
Troponin increasedInvestigations
DehydrationMetabolism and nutrition disorders
HypokalaemiaMetabolism and nutrition disorders
Pancreatic carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute kidney injuryRenal and urinary disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
HypertensionVascular disorders
EmbolismVascular disorders
Other adverse events (124 terms — click to expand)

ReactionSystemPh1b - Refametinib/Regoraf…Ph1b - Refametinib/Regoraf…Ph1b - Refametinib/Regoraf…
DiarrhoeaGastrointestinal disorders
FatigueGeneral disorders
Aspartate aminotransferase increasedInvestigations
Blood creatine phosphokinase increasedInvestigations
HypoalbuminaemiaMetabolism and nutrition disorders
Decreased appetiteMetabolism and nutrition disorders
RashSkin and subcutaneous tissue disorders
AnaemiaBlood and lymphatic system disorders
Abdominal painGastrointestinal disorders
NauseaGastrointestinal disorders
Urinary tract infectionInfections and infestations
ConstipationGastrointestinal disorders
PyrexiaGeneral disorders
Blood creatinine increasedInvestigations
Lipase increasedInvestigations
Weight decreasedInvestigations
DehydrationMetabolism and nutrition disorders
HypomagnesaemiaMetabolism and nutrition disorders
Muscle spasmsMusculoskeletal and connective tissue disorders
Dermatitis acneiformSkin and subcutaneous tissue disorders
HypertensionVascular disorders
ThrombocytopeniaBlood and lymphatic system disorders
HypothyroidismEndocrine disorders
Dry eyeEye disorders
Dry mouthGastrointestinal disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
VomitingGastrointestinal disorders
ChillsGeneral disorders
Mucosal inflammationGeneral disorders
Oedema peripheralGeneral disorders
Alanine aminotransferase increasedInvestigations
Blood alkaline phosphatase increasedInvestigations
HypokalaemiaMetabolism and nutrition disorders
HyponatraemiaMetabolism and nutrition disorders
HypophosphataemiaMetabolism and nutrition disorders
Back painMusculoskeletal and connective tissue disorders
PresyncopeNervous system disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Dyspnoea exertionalRespiratory, thoracic and mediastinal disorders
AlopeciaSkin and subcutaneous tissue disorders

Most-reported serious reactions: Blood creatine phosphokinase increased, Cholangitis, Urinary tract infection, Wound infection, Troponin increased, Dehydration, Hypokalaemia, Pancreatic carcinoma.

Data from ClinicalTrials.gov NCT02168777 adverse events section.

Sponsor's own description

Phase I: Determine the maximum tolerated dose of combination of Regorafenib with Refametinib through a dose escalation study, all tumor types that meet certain inclusion/exclusion criteria can be entered. After the recommended dose is determined, the Phase II portion of the study will evaluate tolerability and efficacy of the combination treatment in patients with breast cancer, lung cancer, or colorectal cancer, respectively.

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Therapy for Cancer: Strategy of Combining Anti-Angiogenic and Target Therapies.
    Comunanza V, Bussolino F. · · 2017 · cited 62× · PMID 29270405 · DOI 10.3389/fcell.2017.00101
  2. Sarcoma Cell Line Screen of Oncology Drugs and Investigational Agents Identifies Patterns Associated with Gene and microRNA Expression.
    Teicher BA, Polley E, Kunkel M, Evans D, et al · · 2015 · cited 52× · PMID 26351324 · DOI 10.1158/1535-7163.mct-15-0074
  3. Predicting Potential Drugs for Breast Cancer based on miRNA and Tissue Specificity.
    Yu L, Zhao J, Gao L. · · 2018 · cited 47× · PMID 29989066 · DOI 10.7150/ijbs.23350
  4. Evidence-based medical oncology and interventional radiology paradigms for liver-dominant colorectal cancer metastases.
    Sag AA, Selcukbiricik F, Mandel NM. · · 2016 · cited 26× · PMID 27003990 · DOI 10.3748/wjg.v22.i11.3127
  5. Preliminary Safety, Pharmacokinetics, and Efficacy of Regorafenib, Cisplatin, and Pemetrexed in Patients With Advanced Nonsquamous Non-Small-Cell Lung Cancers.
    Hellmann MD, Sturm I, Trnkova ZJ, Lettieri J, et al · · 2015 · cited 9× · PMID 26003007 · DOI 10.1016/j.cllc.2015.04.003
  6. Targeting <i>KRAS</i> in pancreatic adenocarcinoma: Progress in demystifying the holy grail.
    Elhariri A, Alhaj A, Ahn D, Sonbol MB, et al · · 2023 · cited 5× · PMID 37700806 · DOI 10.5306/wjco.v14.i8.285

Verify or expand the search:

Other trials of Refametinib (BAY86-9766)

Trials testing the same drug.

Other recruiting trials for Neoplasms

Currently open trials in the same condition.

Other Bayer trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

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/NCT02168777.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing