Clinical Trials /

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

NCT02168777

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.

Related Conditions:
  • Breast Carcinoma
  • Colorectal Carcinoma
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Terminated

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Refametinib (BAY86-9766) in Combination With Regorafenib (Stivarga, BAY73-4506) in Patients With Advanced or Metastatic Cancer
  • Official Title: A Phase 1b/2, Multi-center, Uncontrolled, Open-label, Dose Escalation Study of Refametinib (BAY86-9766) in Combination With Regorafenib (BAY73-4506) in Patients With Advanced or Metastatic Cancer

Clinical Trial IDs

  • ORG STUDY ID: 17064
  • SECONDARY ID: 2013-004861-15
  • NCT ID: NCT02168777

Conditions

  • Neoplasms

Interventions

DrugSynonymsArms
Refametinib (BAY86-9766)Ph1b-Refametinib/Regorafenib Cohort 0
Regorafenib (Stivarga, BAY73-4506)Ph1b-Refametinib/Regorafenib Cohort 0

Purpose

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.

Detailed Description

      Number of treatment-emergent Adverse Events (AEs) will be reported in Adverse Events section.

      Study was originally designed with both Phase I and Phase II part, but sponsor decided not to
      conduct Phase 2 part due to strategic portfolio re-prioritization.
    

Trial Arms

NameTypeDescriptionInterventions
Ph1b-Refametinib/Regorafenib Cohort 0ExperimentalPhase 1b part of study: Participants received different doses of Refametinib and Regorafenib combination therapy to determine recommended Phase 2 dose (RP2D) via dose-escalation. Cohort 0: Refametinib 30mg twice daily (b.i.d) + Regorafenib 80mg once daily (q.d), 3 weeks on/1 week off.
  • Refametinib (BAY86-9766)
  • Regorafenib (Stivarga, BAY73-4506)
Ph1b-Refametinib/Regorafenib Cohort -1ExperimentalPhase 1b part of study: Participants received different doses of Refametinib and Regorafenib combination therapy to determine recommended Phase 2 dose (RP2D) via dose-escalation. Cohort -1: Refametinib 20mg b.i.d + Regorafenib 80mg q.d, 3 weeks on/1 week off.
  • Refametinib (BAY86-9766)
  • Regorafenib (Stivarga, BAY73-4506)
Ph1b-Refametinib/Regorafenib Cohort -1aExperimentalPhase 1b part of study: Participants received different doses of Refametinib and Regorafenib combination therapy to determine recommended Phase 2 dose (RP2D) via dose-escalation. Cohort -1a: Refametinib 20mg b.i.d + Regorafenib 120mg q.d, 3 weeks on/1 week off.
  • Refametinib (BAY86-9766)
  • Regorafenib (Stivarga, BAY73-4506)

Eligibility Criteria

        Inclusion Criteria:

          -  Criteria for the Phase 1b:

               -  Patients with locally advanced or metastatic solid tumors who have either
                  relapsed following, or progressed through, standard therapy; have a current
                  disease state for which there is no standard effective therapy; is not a
                  candidate for, or is unwilling to undergo, standard therapy in cases where no
                  curative option exists.

          -  Cohort-specific criteria for Phase 2:

               -  CRC (Colorectal cancer): Patients with metastatic CRC and known KRAS (Kirsten rat
                  sarcoma viral oncogene homolog) status who are eligible for treatment with
                  regorafenib in accordance with the approved labeling.

               -  NSCLC (Non-small-cell lung cancer): Patients with NSCLC and known KRAS status
                  after platinum based chemotherapy.

               -  Breast cancer: Patients with Her-2 negative breast cancer after anthracycline and
                  taxane based chemotherapy.

          -  Baseline tumor tissue to conduct molecular and / or genetic studies should be
             available from all study patients enrolled in this study. (optional in Phase 1b)

          -  Patients must have at least one uni-dimensional measurable lesion by CT or MRI
             according to Response Evaluation Criteria in Solid Tumors (RECIST)version 1.1.
             (applicable only in Phase 2)

          -  Male or female patients ≥ 18 years of age (only female patients in breast cancer
             cohort of Phase 2).

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

          -  Life expectancy of at least 3 months

          -  Adequate bone marrow, liver and renal function

          -  Cardiac function within normal range

        Exclusion Criteria:

          -  Prior treatment with refametinib or regorafenib.

          -  Metastatic brain or meningeal tumors

          -  Uncontrolled hypertension despite optimal medical management

          -  History of cardiac disease

          -  Arterial or venous thrombotic or embolic events

          -  Any hemorrhage or bleeding event

          -  History or current evidence of retinal vein occlusion (RVO) or central serous
             retinopathy (CSR).

          -  Any condition that was unstable or which could jeopardize the safety of the patient
             and his/her compliance in the study.

          -  Excluded previous therapies and medications:

               -  Radiotherapy within 3 weeks prior to start of treatment

               -  Systemic anticancer therapy including cytotoxic therapy, signal transduction
                  inhibitors, immunotherapy, and hormonal therapy during this trial or within 28
                  days or 5 drug half-lives (if drug half-life in patients is known), whichever is
                  shorter (or within 6 weeks for mitomycin C) before start of the study treatment
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Drug Concentration in Plasma After Multiple Dose (Cmax,md) for Refametinib
Time Frame:Cycle 1 Day 21 at 0 (pre-dose), 0.5, 1, 2, 4, 8 and 12 hours post-dose
Safety Issue:
Description:Maximum drug concentration in plasma after multiple dose for Refametinib. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.

Secondary Outcome Measures

Measure:Maximum Drug Concentration in Plasma After Single (First) Dose (Cmax) for Refametinib and Its Metabolite M-11
Time Frame:Cycle 1 Day 1 at 0 (pre-dose), 0.5, 1, 2, 4 and 8 hours post-dose
Safety Issue:
Description: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.
Measure:Time to Reach Maximum Drug Concentration in Plasma After Single (First) Dose (Tmax) for Refametinib and Its Metabolite M-11
Time Frame:Cycle 1 Day 1 at 0 (pre-dose), 0.5, 1, 2, 4 and 8 hours post-dose
Safety Issue:
Description: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.
Measure:Area Under the Plasma Concentration-time Curve From 0 to 8 h (AUC(0-8)) After Single (First) Dose for Refametinib and Its Metabolite M-11
Time Frame:Cycle 1 Day 1 at 0 (pre-dose), 0.5, 1, 2, 4 and 8 hours post-dose
Safety Issue:
Description:Area under the plasma concentration-time curve from 0 to 8 h after single (first) dose for Refametinib and its metabolite M-11. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measure:Time to Reach Maximum Drug Concentration in Plasma After Multiple Dose (Tmax,md) for Refametinib and Its Metabolite M-11
Time Frame:Cycle 1 Day 21 at 0 (pre-dose), 0.5, 1, 2, 4, 8 and 12 hours post-dose
Safety Issue:
Description:Time to reach maximum drug concentration in plasma after multiple dose for Refametinib and its metabolite M-11. Median and full range were reported.
Measure:Maximum Drug Concentration in Plasma After Single (First) Dose (Cmax) for Regorafenib and Its Metabolites M-2 and M-5
Time Frame:Cycle 1 Day 1 at 0 (pre-dose), 0.5, 1, 2, 4, 8 and 24 hours post-dose
Safety Issue:
Description:Maximum drug concentration in plasma after single (first) dose for Regorafenib and its metabolites M-2 and M-5. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measure:Time to Reach Maximum Drug Concentration in Plasma After Single (First) Dose (Tmax) for Regorafenib and Its Metabolites M-2 and M-5
Time Frame:Cycle 1 Day 1 at 0 (pre-dose), 0.5, 1, 2, 4, 8 and 24 hours post-dose
Safety Issue:
Description:Time to reach maximum drug concentration in plasma after single (first) dose for Regorafenib and its metabolites M-2 and M-5. Median and full range were reported.
Measure:Area Under the Plasma Concentration-time Curve From 0 to 24 h (AUC(0-24)) After Single (First) Dose for Regorafenib and Its Metabolites M-2 and M-5
Time Frame:Cycle 1 Day 1 at 0 (pre-dose), 0.5, 1, 2, 4, 8 and 24 hours post-dose
Safety Issue:
Description:Area under the plasma concentration-time curve from 0 to 24 h after single (first) dose for Regorafenib and its metabolites M-2 and M-5. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measure:Time to Reach Maximum Drug Concentration in Plasma After Multiple Dose (Tmax,md) for Regorafenib and Its Metabolites M-2 and M-5
Time Frame:Cycle 1 Day 21 at 0 (pre-dose), 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose
Safety Issue:
Description:Time to reach maximum drug concentration in plasma after multiple dose for Regorafenib and its metabolites M-2 and M-5. Median and full range were reported.
Measure:Tumor Response During Phase 1b as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Time Frame:From start of treatment until progression is documented
Safety Issue:
Description:Tumor Response was defined as the best tumor response (Complete Response (CR), Partial Response (PR), Stable Disease (SD) or Progressive Disease (PD)) observed during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST). CR was defined as disappearance of all target and non-target tumor lesions, PR was defined as a decrease of at least 30% in the sum of diameters of target lesions, SD was defined neither sufficient shrinkage for PR nor sufficient increase for PD, PD was defined as an increase of at least 20% in the sum of diameters of target lesions.
Measure:Overall Survival During Phase 2
Time Frame:Up to 12 months after last patient first visit
Safety Issue:
Description:Overall survival (OS) was defined as the time (days) from the treatment start date to the date of death due to any cause. For participants who were still alive or who were lost to follow-up as of the database cutoff date for the primary completion, OS was censored at the last known alive date on or prior to the database cutoff date.
Measure:Time to Progression During Phase 2
Time Frame:From start of treatment until progression is documented
Safety Issue:
Description:Time to progression was defined as the time (days) from the treatment start date to the disease progression on or following the start date. Participants not experiencing progression at the database cutoff date for primary completion were censored at the last assessment.
Measure:Progression-free Survival During Phase 2
Time Frame:From start of treatment until progression is documented
Safety Issue:
Description:Progression-free survival was defined as the time from date of treatment assignment to date of first observed disease progression or death due to any cause, if death occurred while the participant was in the study and before progression was observed.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Terminated
Lead Sponsor:Bayer

Trial Keywords

  • Patients with Cancer

Last Updated

June 25, 2017