Clinical Trials /

LY3022855 With BRAF/MEK Inhibition in Patients With Melanoma

NCT03101254

Description:

This research study is studying a combination of targeted therapies as a possible treatment for advanced melanoma that was found to have a BRAF V600E or BRAF V600K genetic mutation The interventions involved in this study are: - LY3022855 - Vemurafenib - Cobimetinib

Related Conditions:
  • Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: LY3022855 With BRAF/MEK Inhibition in Patients With Melanoma
  • Official Title: A Phase I/II Study of LY3022855 With BRAF/MEK Inhibition in Patients With Melanoma

Clinical Trial IDs

  • ORG STUDY ID: 17-030
  • NCT ID: NCT03101254

Conditions

  • Melanoma

Interventions

DrugSynonymsArms
LY3022855LY3022855 + Vemurafenib + Cobimetinib
VemurafenibZelborafLY3022855 + Vemurafenib + Cobimetinib
CobimetinibCotellicLY3022855 + Vemurafenib + Cobimetinib

Purpose

This research study is studying a combination of targeted therapies as a possible treatment for advanced melanoma that was found to have a BRAF V600E or BRAF V600K genetic mutation The interventions involved in this study are: - LY3022855 - Vemurafenib - Cobimetinib

Detailed Description

      This is a Phase I/II clinical trial. A Phase I clinical trial tests the safety of an
      investigational intervention and also tries to define the appropriate dose of the
      investigational intervention to use for further studies. "Investigational" means that the
      intervention is being studied.

      The FDA (the U.S. Food and Drug Administration) has not approved LY3022855 as a treatment for
      any disease.

      The FDA has approved vemurafenib and cobimetinib as treatment options for this disease.

      LY3022855 is a colony-stimulating factor-1 receptor (CSF-1R) inhibitor. It is a human
      monoclonal antibody. A monoclonal antibody is a type of protein made in the laboratory that
      can locate and bind to substances in the body, including tumor cells. By binding to the tumor
      cells, the antibody might prevent the tumor cell from growing and spreading. LY3022855 is
      being developed as a treatment for patients with advanced cancer.

      Vemurafenib and cobimetinib attack different proteins that promote the growth of cancerous
      cells. Vemurafenib is a BRAF inhibitor that works by blocking altered BRAF proteins from
      stimulating the growth of melanoma cancer cells. Cobimetinib works by blocking a protein
      called MEK that has been known to promote melanoma growth. In order to participate in the
      study, participant's disease needs to be tested positive for a mutation (a permanent change
      in the DNA sequence of a gene) of the BRAF gene that belongs to a class of genes known as
      oncogenes. When mutated, oncogenes have the potential to cause normal cells to become
      cancerous. Once the BRAF gene is mutated, the normal functioning of the BRAF protein may be
      changed.

      In this research study, the investigators are combining LY3022855 with vemurafenib and
      cobimetinib in the hopes that the LY3022855 will enhance how your cancer responds to
      vemurafenib and cobimetinib.
    

Trial Arms

NameTypeDescriptionInterventions
LY3022855 + Vemurafenib + CobimetinibExperimentalLY3022855 administered intravenously every week Vemurafenib administered by mouth twice daily Cobimetinib administered by mouth once daily on days 1-21of each cycle
  • LY3022855
  • Vemurafenib
  • Cobimetinib

Eligibility Criteria

        Inclusion Criteria:

          -  For enrollment to the phase I portion: participants must have a histologically
             confirmed melanoma with a BRAF V600E or BRAF V600K mutation (identified via NextGen
             sequencing using the DFCI/BWH OncoPanel or any CLIA-certified method) that is
             metastatic or unresectable and for which standard curative measures do not exist or
             are no longer effective.

          -  For enrollment to the phase II portion: participants must have a histologically
             confirmed melanoma with a BRAF V600E or BRAF V600K mutation (identified via NextGen
             sequencing using the DFCI/BWH OncoPanel or any CLIA-certified method) and cannot have
             received prior BRAF or MEK inhibitor therapy.

          -  Participants enrolling to the phase I portion of the trial must have evaluable or
             measurable disease (see Section 11 for definitions).

          -  Participants enrolling to the phase II portion of the trial must have measurable
             disease, defined as at least one lesion that can be accurately measured in at least
             one dimension (longest diameter to be recorded for non-nodal lesions and short axis
             for nodal lesions) as ≥ 10 mm with spiral CT scan, MRI, or calipers by clinical exam.
             See Section 11 for the evaluation of measurable disease.

          -  Age ≥ 18 years. As no dosing or adverse event data are currently available in
             participants < 18 years of age, children are excluded from this study but will be
             eligible for future pediatric trials.

          -  ECOG performance status 0 - 1 (see APPENDIX A).

          -  Participants must have normal organ and marrow function as defined below:

          -  Absolute neutrophil count ≥ 1.5 K/uL

          -  Platelets ≥ 100 K/uL

          -  Hemoglobin ≥ 9 g/dL

          -  Total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN)

          -  AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional ULN

          -  Serum creatinine ≤ 1.5 × institutional ULN

          -  PT-INR ≤ 1.5 × institutional ULN (for participants on anticoagulation therapy, ≤ 1.5 ×
             their baseline value)

          -  aPTT ≤ 1.5 × institutional ULN (for participants on anticoagulation therapy, ≤ 1.5 ×
             their baseline value)

          -  Participants must have a left ventricular ejection fraction (LVEF) ≥ 50%.

          -  Participants must have a QTc of ≤ 470 msec on the screening EKG.

          -  The effects of LY3022855 on the developing human fetus are unknown. For this reason
             and because anti-cancer agents are known to be teratogenic, women of child-bearing
             potential and men must agree to use adequate contraception (hormonal or barrier method
             of birth control; abstinence) prior to study entry and for the duration of study
             participation. Should a woman become pregnant or suspect she is pregnant while she or
             her partner is participating in this study, she should inform her treating physician
             immediately. Men treated or enrolled on this protocol must also agree to use adequate
             contraception prior to the study, for the duration of study participation, and 4
             months after completion of LY3022855 administration.

          -  Ability to understand and the willingness to sign a written informed consent document.

          -  Participants must have archival tumor tissue available. Participants without archival
             tissue may be enrolled at the discretion of the principal investigator.

        Exclusion Criteria:

          -  Participants who have had chemotherapy, radiotherapy, biologic therapy, major surgery,
             or another investigational agent within 3 weeks (6 weeks for nitrosoureas or mitomycin
             C) prior to entering the study.

          -  Participants who have not recovered to ≤ CTCAE grade 1 or baseline from toxicity as a
             result of previous cancer treatment prior to entering the study (with the exception of
             alopecia and peripheral neuropathy which can be ≤ grade 2).

          -  For enrollment to the phase II portion: participants who have received prior BRAF or
             MEK inhibitor therapy.

          -  Participants with known untreated brain metastases should be excluded from this
             clinical trial because of their poor prognosis and because they often develop
             progressive neurologic dysfunction that would confound the evaluation of neurologic
             and other adverse events. Participants with a history of brain metastases that have
             been treated, are no longer taking corticosteroids, and have been stable on imaging
             for ≥ 4 weeks following the last date of treatment are permitted.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to LY3022855, vemurafenib, or cobimetinib.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Pregnant women are excluded from this study because LY3022855 is an anti-cancer agent
             with the potential for teratogenic or abortifacient effects. Because there is an
             unknown but potential risk for adverse events in nursing infants secondary to
             treatment of the mother with LY3022855, breastfeeding should be discontinued if the
             mother is treated with LY3022855. These potential risks may also apply to the other
             agents used in this study.

          -  Participants with a known history of HIV are ineligible because of the potential for
             pharmacokinetic interactions with LY3022855, vemurafenib, and cobimetinib with
             antiretroviral agents. In addition, these participants are at increased risk of lethal
             infections when treated with marrow-suppressive therapy. Appropriate studies will be
             undertaken in participants receiving combination antiretroviral therapy when
             indicated.

          -  Participants with a personal or family history of long QT syndrome.

          -  Participants with a history of a second primary malignancy. Exceptions include:
             patients with a history of malignancies that were treated curatively and have not
             recurred within 3 years prior to study entry; resected basal and squamous cell
             carcinomas of the skin, and completely resected carcinoma in situ of any type.

          -  Participants with impairment of GI function or GI disease that may significantly alter
             the absorption of vemurafenib and cobimetinib in the opinion of the treating
             investigator (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea,
             malabsorption syndrome, small bowel resection).

          -  Participants who are unable to swallow or retain oral medication.

          -  Participants that require co-administration of strong or moderate CYP3A inhibitors, as
             these medications may alter vemurafenib and cobimetinib concentrations.

          -  Participants who require treatment with medications that are strong or moderate CYP3A
             inducers, as these medications may alter the concentration of cobimetinib.

          -  Participants with evidence of retinal pathology on ophthalmologic examination that is
             considered a risk factor for neurosensory retinal detachment/central serous
             chorioretinopathy (CSCR), retinal vein occlusion (RVO), or neovascular macular
             degeneration.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival
Time Frame:2 years
Safety Issue:
Description:Time from initiation of study therapy until documentation of disease progression by RECIST criteria

Secondary Outcome Measures

Measure:Toxicity
Time Frame:2 years
Safety Issue:
Description:Ability to give these three medications in combination without a dose limiting side effect. Assessment of side effects that do occur
Measure:Overall Response Rate
Time Frame:2 years
Safety Issue:
Description:Rate of patients with a complete response or partial response as assessed by RECIST criteria
Measure:Partial Response Rate
Time Frame:2 years
Safety Issue:
Description:At least a 30% decrease in the sum of the diameters of target lesions.
Measure:Stable Disease
Time Frame:2 years
Safety Issue:
Description:Disease that is less than a 30% decrease or 20% increase in the sum of the diameters of the target lesions.
Measure:Progressive Disease
Time Frame:2 years
Safety Issue:
Description:At least a 20% increase in the sum of the diameters of target lesions.
Measure:Overall Survival
Time Frame:2 years
Safety Issue:
Description:Time from initiation of study therapy to death.
Measure:Complete response
Time Frame:2 years
Safety Issue:
Description:Disappearance of all target lesions.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • Melanoma

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