Clinical Trials /

Neoadjuvant Vemurafenib + Cobimetinib + Atezolizumab in Melanoma: NEO-VC

NCT02303951

Description:

Evaluation of the efficacy, safety and biologic effects of neo-adjuvant treatment with vemurafenib + cobimetinib in patients with limited metastasis of melanoma in stage IIIC/IV melanoma.

Related Conditions:
  • Melanoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Neoadjuvant Vemurafenib + Cobimetinib in Melanoma: NEO-VC
  • Official Title: Neoadjuvant Treatment With the Combination of Vemurafenib and Cobimetinib in Limited Metastasis of Malignant Melanoma (AJCC Stage IIIC/IV) and Integrated Biomarker Study: a Single Armed Phase II Trial

Clinical Trial IDs

  • ORG STUDY ID: EADO_VC_NEO_1
  • NCT ID: NCT02303951

Conditions

  • Malignant Melanoma

Interventions

DrugSynonymsArms
Vemurafenib + cobimetinibVemurafenib + cobimetinib

Purpose

Evaluation of the efficacy, safety and biologic effects of neo-adjuvant treatment with vemurafenib + cobimetinib in patients with limited metastasis of melanoma in stage IIIC/IV melanoma.

Detailed Description

      Patients with hardly resectable/unresectable limited metastasis in malignant melanoma stages
      IIIC/IV (AJCC 2010) carrying the BRAF V600 mutation, in order to achieve operability are
      enrolled in the NEO-VC-study. The main aim of this study is to achieve operability in a
      higher percentage of patients by neoadjuvant treatment through shrinkage of the tumors.
      Patients with operable stage IV disease show an impressive survival benefit with long term (5
      y.) survival rates around 30 %. Only a percentage of up to 20 % can presently be treated by
      complete metastasectomy. This percentage may be enlarged by pre-treatment with an efficacious
      antitumor drug.
    

Trial Arms

NameTypeDescriptionInterventions
Vemurafenib + cobimetinibExperimentalVemurafenib 960 mg bid orally + cobimetinib 60 mg 21/7 orally (vemurafenib: daily intake; cobimetinib: 3 weeks on drug, 1 week off)
  • Vemurafenib + cobimetinib

Eligibility Criteria

        Inclusion Criteria:

          -  Adult patients, ≥ 18 years of age

          -  Willing and able to give informed consent

          -  Metastatic melanoma, stage IIIC or IV (American Joint Committee on Cancer 2010)

          -  ECOG (Eastern Cooperative Oncology Group ): 0-1

          -  MAP-kinase pathway inhibitor treatment-naïve

          -  Positive for BRAF V600 mutation, preferentially to be shown from metastatic tumor
             tissue

          -  Decision of eligibility for neoadjuvant combined vemurafenib and cobimetinib treatment
             by interdisciplinary tumor board. Patient with limited numbers of metastases and few
             organ systems involved should be selected, making surgical resection after neoadjuvant
             treatment probable.

          -  Measurable disease by Response Evaluation Criteria In Solid Tumors (RECIST V1.1)
             criteria

          -  Adequate hematologic and organ function as defined by:

               -  ANC (absolute neutrophil count ) ≥ 1.5 × 109/L

               -  Platelets ≥ 100 × 109/L

               -  Hemoglobin ≥ 9 g/dL

               -  Albumin ≥ 2.5 g/dL

               -  Bilirubin ≤ 1.5 × the upper limit of normal (ULN)

               -  AST (aspartate aminotransferase), ALT (alanine aminotransferase), and alkaline
                  phosphatase ≤ 3 × ULN, except patients with documented liver metastases:

        AST and/or ALT ≤ 5 × ULN

          -  Patients with documented liver or bone metastases: alkaline phosphatase ≤ 5 × ULN

          -  Serum creatinine ≤ 1.5 × ULN

               -  For fertile men: effective contraception during treat-ment and for 6 months after
                  completion in such a manner that the risk of pregnancy is minimized

               -  For women of childbearing potential, negative pregnancy test performed within 28
                  days prior study enrolment

        Exclusion Criteria:

          -  Candidates for direct surgery: patients with single site easily resectable metastasis

          -  Major surgical procedure or significant traumatic injury within 2 weeks prior to first
             dose of study drug treatment

          -  Active central nervous system metastases ex-cept metastases after complete resection
             or stereotactic irradiation and stable status for at least 3 months

          -  History of carcinomatous meningitis

          -  Severe cardiovascular disease within 6 months prior to study drug administration

          -  History or evidence of cardiovascular risk including any of the following

               -  LVEF (left ventricular ejection fraction ) < 50% or < LLN (lower limit of
                  normal), whichever is lower

               -  a QTc (corrected QT interval ) interval > 450 ms

               -  evidence of clinically significant uncontrolled arrhythmias

          -  History or evidence of retinal vein occlusion

          -  Previous malignancy within 5 years prior to study, except for basal or squamous cell
             carcinoma of the skin, melanoma in-situ, or carcinoma in-situ of the cervix

          -  Psychological, familial, sociological, or geographical conditions that do not permit
             compliance with the protocol

          -  Any condition that is unstable or could jeopardize the safety of the patient and their
             compliance in the study

          -  Legal incapacity or limited legal capacity

          -  Subjects housed in an institution on official or le-gal orders

          -  Participation in another clinical study with experimental therapy within the 30 days
             before start of treatment

          -  Pregnancy or lactation period

          -  Concomitant use of study therapy and drugs with a potential for QT prolongation (see
             database www.qtdrugs.org)

          -  Known immediate or delayed hypersensitivity re-action or idiosyncrasy to cobimetinib
             and/or vemurafenib and/or to any of its excipients

          -  Patients with diseases that affect liver function, such as viral hepatitis

          -  Patients receiving medications known to increase the risk of peripheral edema
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percent of patients who actually become resectable and are resected
Time Frame:Following 18 weeks of combined treatment
Safety Issue:
Description:Percentage of patients becoming operable after the combined treatment within 18 weeks. The primary research question is the difference of this observed proportion with verum-treatment in the study which is compared to an assumed/known proportion without treatment based on an estimation of the scientific community

Secondary Outcome Measures

Measure:Progression free survival time after resection
Time Frame:Following 18 weeks of combined treatment
Safety Issue:
Description:Progression free survival time after resection, in the group who actually underwent complete resection
Measure:Progression free survival
Time Frame:Following 6 and 12 months of combined treatment
Safety Issue:
Description:Progression free survival rates at 6 and 12 months after start of treatment
Measure:Objective response
Time Frame:Up to 29 months
Safety Issue:
Description:Rate of objective responses
Measure:Tolerability (Number of patients with adverse events and number of patients who prematurely discontinued treatment due to adverse events)
Time Frame:Up to 29 months
Safety Issue:
Description:Number of patients with adverse events and number of patients who prematurely discontinued treatment due to adverse events
Measure:Overall survival
Time Frame:Up to 29 months
Safety Issue:
Description:Overall survival in the total study population
Measure:Progression free survival time
Time Frame:Up to 29 months
Safety Issue:
Description:Progression free survival time in the total study population

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University Hospital Tuebingen

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