stop_circleTerminated/Withdrawn

Neoplasms

Bayer Identifier:

17064

ClinicalTrials.gov Identifier:

NCT02168777

EudraCT Number:

2013-004861-15

EU CT Number:

Not Available
Refametinib (BAY86-9766) in combination with regorafenib (Stivarga, BAY73-4506) in patients with advanced or metastatic cancer

Trial 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.

Key Participants Requirements

Sex

Both

Age

18 - N/A
  • - 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
  • - 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

Trial summary

Enrollment Goal
20
Trial Dates
June 2014 - April 2016
Phase
Phase 1
Could I Receive a placebo
No
Products
Refametinib (BAY86-9766)
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Completed
Houston, 77030, United States
Completed
St. Louis, 63110, United States
Completed
Chapel Hill, 27599, United States
Completed
Detroit, 48201, United States
Completed
New Haven, 06510, United States
Withdrawn
Erasmus Medisch CentrumROTTERDAM, 3015 CE, Netherlands
Withdrawn
Universitätsklinikum KölnKöln, 50937, Germany
Withdrawn
LMU Klinikum der Universität München - GroßhadernMünchen, 81377, Germany
Withdrawn
Medizinische Fakultät Carl Gustav CarusDresden, 01307, Germany
Withdrawn
MarienhospitalStuttgart, 70199, Germany
Withdrawn
A.O.U. San Luigi GonzagaOrbassano, 10043, Italy
Withdrawn
IRCCS Istituto Clinico HumanitasRozzano, 20089, Italy
Withdrawn
A.O. San GerardoMonza, 20900, Italy
Withdrawn
A.O.U. di BolognaBologna, 40138, Italy
Withdrawn
A.O.U. PisanaPisa, 56126, Italy
Withdrawn
Fondazione Poliambulanza - Istituto OspedalieroBrescia, 25124, Italy
Withdrawn
Università Cattolica del Sacro CuoreRoma, 00168, Italy
Withdrawn
Hadassah Hebrew University Hospital Ein KeremJerusalem, 9112001, Israel
Withdrawn
Rabin Medical Center - Beilinson CampusPetah Tikva, 4941492, Israel
Withdrawn
Tel-Aviv Sourasky Medical CenterTel Aviv, 6423906, Israel
Withdrawn
Rambam Health CorporationHaifa, 3109601, Israel
Withdrawn
Meir Medical CenterKfar Saba, 4428164, Israel
Withdrawn
Chaim Sheba Medical CenterRamat Gan, 5262000, Israel
Withdrawn
Centre René Gauducheau - NantesNANTES, 44805, France
Withdrawn
Institut de Cancérologie de l’Ouest (ICO)ANGERS CEDEX, 49933, France
Withdrawn
Centre Oscar Lambret - LilleLILLE CEDEX, 59020, France
Withdrawn
Centre Léon BérardLYON CEDEX, 69008, France
Withdrawn
Hôpital Henri Mondor - CréteilCRETEIL CEDEX, 94000, France
Withdrawn
Institut du Cancer de MontpellierMONTPELLIER Cedex 5, 34298, France
Withdrawn
Hôpital de Rangueil - ToulouseTOULOUSE CEDEX 9, 31059, France
Withdrawn
Institut Claudius Regaud - iUCT OncopoleTOULOUSE CEDEX 9, 31059, France
Withdrawn
Universitätsklinikum UlmUlm, 89091, Germany
Withdrawn
Klinikum Oldenburg GmbHOldenburg, 26133, Germany
Withdrawn
Scientific Research Instutute of Oncology n.a. N.N. PetrovSt. Petersburg, 197758, Russia
Withdrawn
Russian Oncological Scientific Center n.a. N.N. Blokhin RAMSMoscow, 115478, Russia
Withdrawn
Russian Oncological Scientific Center n.a. N.N. Blokhin RAMSMoscow, 115478, Russia
Withdrawn
Central Clinical Hospital #2 n.a. Semashko of JSC "RRW"Moscow, 129128, Russia
Withdrawn
Leningrad Regional Oncology DispensarySt. Petersburg, 191104, Russia

Primary Outcome

  • Maximum drug concentration in plasma after multiple dose (Cmax,md) for Refametinib
    Maximum drug concentration in plasma after multiple dose for Refametinib. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
    date_rangeTime Frame:
    Cycle 1 Day 21 at 0 (pre-dose), 0.5, 1, 2, 4, 8 and 12 hours post-dose
    enhanced_encryption
    Safety Issue:
    No
  • Maximum drug concentration in plasma after multiple dose (Cmax,md) for Refametinib metabolite M-11
    Maximum drug concentration in plasma after multiple dose for Refametinib metabolite M-11. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
    date_rangeTime Frame:
    Cycle 1 Day 21 at 0 (pre-dose), 0.5, 1, 2, 4, 8 and 12 hours post-dose
    enhanced_encryption
    Safety Issue:
    No
  • Area under the plasma concentration-time curve from 0 to 12 h after multiple dose (AUC(0-12)md) for Refametinib
    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.
    date_rangeTime Frame:
    Cycle 1 Day 21 at 0 (pre-dose), 0.5, 1, 2, 4, 8 and 12 hours post-dose
    enhanced_encryption
    Safety Issue:
    No
  • Area under the plasma concentration-time curve from 0 to 12 h after multiple dose (AUC(0-12)md) for Refametinib metabolite M-11
    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.
    date_rangeTime Frame:
    Cycle 1 Day 21 at 0 (pre-dose), 0.5, 1, 2, 4, 8 and 12 hours post-dose
    enhanced_encryption
    Safety Issue:
    No
  • Maximum drug concentration in plasma after multiple dose (Cmax,md) for Regorafenib
    Maximum drug concentration in plasma after multiple dose for Regorafenib. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
    date_rangeTime Frame:
    Cycle 1 Day 21 at 0 (pre-dose), 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose
    enhanced_encryption
    Safety Issue:
    No
  • Maximum drug concentration in plasma after multiple dose (Cmax,md) for Regorafenib metabolite M-2
    Maximum drug concentration in plasma after multiple dose for Regorafenib metabolite M-2. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
    date_rangeTime Frame:
    Cycle 1 Day 21 at 0 (pre-dose), 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose
    enhanced_encryption
    Safety Issue:
    No
  • Maximum drug concentration in plasma after multiple dose (Cmax,md) for Regorafenib metabolite M-5
    Maximum drug concentration in plasma after multiple dose for Regorafenib metabolite M-5. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
    date_rangeTime Frame:
    Cycle 1 Day 21 at 0 (pre-dose), 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose
    enhanced_encryption
    Safety Issue:
    No
  • Area under the plasma concentration-time curve from 0 to 24 h after multiple dose (AUC(0-24)md) for Regorafenib
    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.
    date_rangeTime Frame:
    Cycle 1 Day 21 at 0 (pre-dose), 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose
    enhanced_encryption
    Safety Issue:
    No
  • Area under the plasma concentration-time curve from 0 to 24 h after multiple dose (AUC(0-24)md) for Regorafenib metabolite M-2
    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.
    date_rangeTime Frame:
    Cycle 1 Day 21 at 0 (pre-dose), 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose
    enhanced_encryption
    Safety Issue:
    No
  • Area under the plasma concentration-time curve from 0 to 24 h after multiple dose (AUC(0-24)md) for Regorafenib metabolite M-5
    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.
    date_rangeTime Frame:
    Cycle 1 Day 21 at 0 (pre-dose), 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose
    enhanced_encryption
    Safety Issue:
    No
  • Tumor response during Phase 2 as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
    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) criteria. CR was defined as disappearance of tumor lesions, PR was defined as a decrease of at least 30% in the sum of tumor lesion sizes, SD was defined as steady state of disease, PD was defined as an increase of at least 20% in the sum of tumor lesions sizes.
    date_rangeTime Frame:
    Up to 12 months
    enhanced_encryption
    Safety Issue:
    No
  • Number of participants with dose limiting toxicities (DLTs)
    Dose-limiting toxicities (DLTs) were analyzed in the maximum tolerated dose (MTD) analysis set, in which only the six first patients of each dose escalation Cohort could be included according to the modified Rolling-6 method that was applied in this study.
    date_rangeTime Frame:
    At Cycle 1
    enhanced_encryption
    Safety Issue:
    Yes

Secondary Outcome

  • Maximum drug concentration in plasma after single (first) dose (Cmax) for Refametinib and its metabolite M-11
    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.
    date_rangeTime Frame:
    Cycle 1 Day 1 at 0 (pre-dose), 0.5, 1, 2, 4 and 8 hours post-dose
    enhanced_encryption
    Safety Issue:
    No
  • Time to reach maximum drug concentration in plasma after single (first) dose (tmax) for Refametinib and its metabolite M-11
    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.
    date_rangeTime Frame:
    Cycle 1 Day 1 at 0 (pre-dose), 0.5, 1, 2, 4 and 8 hours post-dose
    enhanced_encryption
    Safety Issue:
    No
  • 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
    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.
    date_rangeTime Frame:
    Cycle 1 Day 1 at 0 (pre-dose), 0.5, 1, 2, 4 and 8 hours post-dose
    enhanced_encryption
    Safety Issue:
    No
  • Time to reach maximum drug concentration in plasma after multiple dose (tmax,md) for Refametinib and its metabolite M-11
    Time to reach maximum drug concentration in plasma after multiple dose for Refametinib and its metabolite M-11. Median and full range were reported.
    date_rangeTime Frame:
    Cycle 1 Day 21 at 0 (pre-dose), 0.5, 1, 2, 4, 8 and 12 hours post-dose
    enhanced_encryption
    Safety Issue:
    No
  • Maximum drug concentration in plasma after single (first) dose (Cmax) for Regorafenib and its metabolites M-2 and M-5
    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.
    date_rangeTime Frame:
    Cycle 1 Day 1 at 0 (pre-dose), 0.5, 1, 2, 4, 8 and 24 hours post-dose
    enhanced_encryption
    Safety Issue:
    No
  • Time to reach maximum drug concentration in plasma after single (first) dose (tmax) for Regorafenib and its metabolites M-2 and M-5
    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.
    date_rangeTime Frame:
    Cycle 1 Day 1 at 0 (pre-dose), 0.5, 1, 2, 4, 8 and 24 hours post-dose
    enhanced_encryption
    Safety Issue:
    No
  • 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
    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.
    date_rangeTime Frame:
    Cycle 1 Day 1 at 0 (pre-dose), 0.5, 1, 2, 4, 8 and 24 hours post-dose
    enhanced_encryption
    Safety Issue:
    No
  • Time to reach maximum drug concentration in plasma after multiple dose (tmax,md) for Regorafenib and its metabolites M-2 and M-5
    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.
    date_rangeTime Frame:
    Cycle 1 Day 21 at 0 (pre-dose), 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose
    enhanced_encryption
    Safety Issue:
    No
  • Tumor response during Phase 1b as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
    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 disappeareance 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.
    date_rangeTime Frame:
    From start of treatment until progression is documented
    enhanced_encryption
    Safety Issue:
    No
  • Overall survival during Phase 2
    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.
    date_rangeTime Frame:
    Up to 12 months after last patient first visit
    enhanced_encryption
    Safety Issue:
    No
  • Time to progression during Phase 2
    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.
    date_rangeTime Frame:
    From start of treatment until progression is documented
    enhanced_encryption
    Safety Issue:
    No
  • Progression-free survival during Phase 2
    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.
    date_rangeTime Frame:
    From start of treatment until progression is documented
    enhanced_encryption
    Safety Issue:
    No

Trial design

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
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Treatment
Allocation
Non-randomized
Blinding
Open Label
Assignment
Parallel Assignment
Trial Arms
3

Additional Information

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