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Trial record 20 of 2147 for:    Melanoma

Abbreviated MAPK Targeted Therapy Plus Pembrolizumab in Melanoma

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ClinicalTrials.gov Identifier: NCT03149029
Recruitment Status : Recruiting
First Posted : May 11, 2017
Last Update Posted : May 8, 2018
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Ryan Sullivan, M.D., Massachusetts General Hospital

Brief Summary:

This research study is studying a combination of drugs as a possible treatment for unresectable or metastatic melanoma.

The drugs involved in this study are:

  • Pembrolizumab (Keytruda)
  • Trametinib (Mekinist)
  • Dabrafenib (Tafinlar)

Condition or disease Intervention/treatment Phase
Metastatic Melanoma Drug: Pembrolizumab Drug: Dabrafenib Drug: Trametinib Phase 2

Detailed Description:
  • This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.
  • The FDA (the U.S. Food and Drug Administration) has approved pembrolizumab, dabrafenib, and trametinib for this specific disease but the combination of all three has not been approved.
  • This study is being conducted to document whether trametinib with or without dabrafenib taken for brief period of time prior to and with pembrolizumab works better than the investigators expect pembrolizumab to work in participants with unresectable and/or metastatic melanoma. All three of these drugs are FDA-approved for unresectable and/or metastatic melanoma; however, they are not FDA-approved for use all together.

    • Pembrolizumab is a type of antibody that inhibits the cancer cell growth. An antibody is a cell that attaches to other cells to fight off infection.
    • Trametinib is a cell inhibitor that binds to the cancer cells to inhibit the cancer cells' signals to decrease cell growth.
    • Dabrafenib is also a cell inhibitor and works by stopping the cancer cell from duplicating.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Trial of Abbreviated MAPK Targeted Therapy Plus Pembrolizumab in Patients With Unresectable or Metastatic Melanoma
Actual Study Start Date : November 27, 2017
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : December 31, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma

Arm Intervention/treatment
Experimental: BRAFV600 mutant
  • Pembrolizumab administered intravenously every three weeks
  • Dabrafenib taken every twelve hours orally
  • Trametinib taken every twelve hours orally
Drug: Pembrolizumab
Pembrolizumab is a type of antibody that inhibits the cancer cell growth
Other Name: Keytruda

Drug: Dabrafenib
Dabrafenib is also a cell inhibitor and works by stopping the cancer cell from duplicating
Other Name: Tafinlar

Drug: Trametinib
Trametinib is a cell inhibitor that binds to the cancer cells to inhibit the cancer cells' signals to decrease cell growth
Other Name: Mekinist

Experimental: BRAFV600 wild type
  • Pembrolizumab administered intravenously every three weeks
  • Trametinib taken every twelve hours orally
Drug: Pembrolizumab
Pembrolizumab is a type of antibody that inhibits the cancer cell growth
Other Name: Keytruda

Drug: Trametinib
Trametinib is a cell inhibitor that binds to the cancer cells to inhibit the cancer cells' signals to decrease cell growth
Other Name: Mekinist




Primary Outcome Measures :
  1. The rate of clinical benefit [ Time Frame: 6 months ]
    Rate of complete response, partial response, stable disease


Secondary Outcome Measures :
  1. Overall Survival [ Time Frame: 2 years ]
  2. Safety and Tolerability: AE and SAE rate by CTCAE4 [ Time Frame: 2 years ]
    AE and SAE rate by CTCAE4

  3. Complete Response (CR) Rate [ Time Frame: 2 years ]
    CR by RECIST1.1

  4. Partial Response (PR) Rate [ Time Frame: 2 years ]
    PR by RECIST1.1

  5. Stable Disease (SD) Rate [ Time Frame: 2 years ]
    SD by RECIST1.1



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participants must have histologically confirmed metastatic or unresectable melanoma.
  • Participants 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) as ≥ 20 mm with conventional techniques or as ≥10 mm with spiral CT scan. See section 11 for the evaluation of measureable disease.
  • Participants may have previously received ipilimumab, adjuvant anti-PD1 therapy, or high-dose IL-2. They may not have previously been treated with BRAF inhibitors (vemurafenib, dabrafenib, encorafenib), MEK inhibitors (selumetinib, trametinib, binimetinib, cobimetinib), and/or anti-PD1/PDL1 monoclonal antibodies for metastatic or unresectable disease. Participants must allow 2 weeks between prior chemotherapy targeted small molecule therapy, or radiation therapy prior to study Day 1 or recovery (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.

    • Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
    • Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
  • Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of the combination of trametinib with or without dabrafenib, and pembrolizumab in participants less than 18 years of age, children are excluded from this study.
  • ECOG performance status ≤1.
  • Life expectancy of greater than three months.
  • Participants must have normal organ and marrow function as defined below:

    • Leukocytes ≥ 3,000/mcL
    • Absolute neutrophil count ≥ 1,500/mcL
    • Platelets ≥ 100,000/mcL
    • total bilirubin ≤ 1.5 X institutional upper limits of normal; total bilirubin > 1.5X above institutional upper limits of normal will be allowed if direct bilirubin is within normal limits or if patients has a documented history of Gilbert's disease
    • AST (SGOT)/ALT (SGPT) ≤ 2.5 X institutional upper limit of normal
    • Creatinine within normal institutional limits or creatinine clearance ≥ 60 mL/min/1.73 m2 for subjects with creatinine levels about institutional normal.
  • Participants must have BRAFV600-mutation status known.
  • Participants must have disease amenable to and be willing to undergo serial core or excisional biopsies of a tumor lesion(s).
  • Because both dabrafenib and trametinib are class D agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with either dabrafenib and trametinib, breastfeeding should be discontinued if the mother is treated with either dabrafenib, trametinib, or the combination of dabrafenib and trametinib. Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year. 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. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Participants treated with prior chemotherapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.

    • Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
    • Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
  • Participants previously treated with BRAF inhibitors (vemurafenib, dabrafenib, encorafenib), MEK inhibitors (selumetinib, trametinib, binimetinib, cobimetinib), and/or anti-PD1/PDL1 monoclonal antibodies for metastatic or unresectable disease. Any other prior therapy will be allowed (including ipilimumab, adjuvant anti-PD1 therapy, high-dose IL-2).
  • Participants with symptomatic brain metastases will 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. Subjects with asymptomatic, stable brain metastases and/or who have been previously treated for these conditions that are asymptomatic in the absence of corticosteroid therapy are allowed to enroll. Brain metastasis must be stable with verification by imaging (brain MRI completed at screening demonstrating no current evidence of progressive brain metastases.
  • Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
  • Patients may not be receiving any other anti-neoplastic agents.
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
  • Pregnant women are excluded from this study because both dabrafenib and trametinib are class D agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with either dabrafenib and trametinib, breastfeeding should be discontinued if the mother is treated with either dabrafenib, trametinib, or the combination of dabrafenib and trametinib.
  • Participants known to be HIV-positive and on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with either dabrafenib or trametinib. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated.
  • Participants who have had major surgery < 2 weeks prior to entering the study.
  • Has a known history of active TB (Bacillus Tuberculosis)
  • Hypersensitivity to pembrolizumab or any of its excipients.
  • No symptomatic or untreated leptomeningeal disease.
  • Participants are not permitted to receive enzyme inducing anti-epileptic drugs.
  • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • Has a history of (non-infectious) pneumonitis that required steroids or current/active pneumonitis.
  • History of current evidence of retinal vein occlusion (RVO) or retinal pigment epithelial detachment (RPED):
  • History of RVO or RPED
  • Visible retinal pathology as assessed by ophthalmic exam that is considered a risk factor for RVO or RPED such as evidence of new optic disc cupping, evidence of visual field defects, and intraocular pressure >21 mm Hg.

    • Uncontrolled intercurrent illness including, but not limited to:
    • Ongoing or active infection
    • LVEF <50% as determined by either MUGA scan or Echo
    • Edema > Grade 1
    • Documented myocardial infarction or unstable/uncontrolled cardiac disease (eg, unstable angina, severe arrhythmias, congestive heart failure [New York Heart Association (NYHA) > Class II]) within 6 months of study entry
    • Arterial thrombosis or vascular ischemic events, such as transient ischemic attack, cerebral infarction, within 6 months prior to study entry
    • Serious or non-healing wound
    • History of any medical condition including cardiovascular disease or chronic obstructive pulmonary disease (COPD), that in the opinion of the investigator, may increase the risks associated with study participation or study treatments or may interfere with the conduct of the study or interpretation of study results
    • Psychiatric illness/social situations that would limit compliance with study requirements
  • Individuals with a history of a different malignancy are ineligible except for the following circumstances.

    • Individuals with a history of other malignancies are eligible if they have been disease-free for at least 3 years and are deemed by the investigator to be at low risk for recurrence of that malignancy.
    • Individuals with the following cancers are eligible if diagnosed and treated within the past 3 years: cervical cancer in situ and basal cell or squamous cell carcinoma of the skin.
  • Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  • Has received a live vaccine within 30 days of planned start of study therapy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03149029


Contacts
Contact: Ryan J Sullivan, MD 617-643-3614 Rsullivan7@partners.org

Locations
United States, Massachusetts
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02115
Contact: David McDermott, MD    617-632-9250      
Principal Investigator: David McDermott, MD         
Massachusetts general Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Ryan J Sullivan, MD    617-643-3614    Rsullivan7@partners.org   
Principal Investigator: Ryan J Sullivan, MD         
Sponsors and Collaborators
Massachusetts General Hospital
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Ryan J Sullivan, MD Massachusetts General Hospital

Responsible Party: Ryan Sullivan, M.D., MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT03149029     History of Changes
Other Study ID Numbers: 16-642
First Posted: May 11, 2017    Key Record Dates
Last Update Posted: May 8, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Ryan Sullivan, M.D., Massachusetts General Hospital:
Metastatic Melanoma

Additional relevant MeSH terms:
Melanoma
Nevi and Melanomas
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Pembrolizumab
Trametinib
Dabrafenib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action