Clinical Trials /

Imiquimod and Pembrolizumab in Treating Patients With Stage IIIB-IV Melanoma

NCT03276832

Description:

This pilot trial studies the side effects and how well imiquimod and pembrolizumab work in treating patients with stage IIIB-IV melanoma. Imiquimod may stimulate the immune system. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Giving imiquimod and pembrolizumab may work better at treating melanoma.

Related Conditions:
  • Cutaneous Melanoma
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Imiquimod and Pembrolizumab in Treating Patients With Stage IIIB-IV Melanoma
  • Official Title: Pilot Study to Test the Safety and Efficacy of the Combination of Imiquimod and Pembrolizumab for the Treatment of Metastatic Melanoma

Clinical Trial IDs

  • ORG STUDY ID: MC1578
  • SECONDARY ID: NCI-2017-01591
  • SECONDARY ID: MC1578
  • SECONDARY ID: P30CA015083
  • NCT ID: NCT03276832

Conditions

  • Metastatic Melanoma
  • Stage IIIB Cutaneous Melanoma AJCC v7
  • Stage IIIC Cutaneous Melanoma AJCC v7
  • Stage IV Cutaneous Melanoma AJCC v6 and v7

Interventions

DrugSynonymsArms
ImiquimodAldara, R 837, S 26308, ZyclaraTreatment (pembrolizumab, imiquimod)
PembrolizumabKeytruda, Lambrolizumab, MK-3475, SCH 900475Treatment (pembrolizumab, imiquimod)

Purpose

This pilot trial studies the side effects and how well imiquimod and pembrolizumab work in treating patients with stage IIIB-IV melanoma. Imiquimod may stimulate the immune system. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Giving imiquimod and pembrolizumab may work better at treating melanoma.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To gain preliminary data of the anti-tumor activity and safety profile of the combination
      of imiquimod and pembrolizumab in patients with unresectable cutaneous melanoma.

      SECONDARY OBJECTIVES:

      I. To compare and contrast (in a hypothesis generating manner) the biomarker profiles of
      patients who have a confirmed complete response (CR) or partial response (PR) by Response
      Evaluation Criteria in Solid Tumors (RECIST) criteria with patients who do not.

      OUTLINE:

      Patients receive pembrolizumab intravenously (IV) on day 1 and apply imiquimod cutaneously on
      days 1-5 (Monday - Friday). Courses repeat every 21 days for up to 2 years (approximately 35
      courses) in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 12 weeks for 2 years.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (pembrolizumab, imiquimod)ExperimentalPatients receive pembrolizumab IV on day 1 and apply imiquimod cutaneously on days 1-5 (Monday - Friday). Courses repeat every 21 days for up to 2 years (approximately 35 courses) in the absence of disease progression or unacceptable toxicity.
  • Imiquimod
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Histological confirmation of stage IIIB, IIIC, IVM1a, IVM1b, or IVM1c that is not
             suitable for surgical resection

          -  Patients must not have received prior pembrolizumab or other anti-PD1/PDL1 therapies
             for their metastatic disease

          -  At least one cutaneous lesion that is amenable to treatment with topical imiquimod

          -  Measurable disease by RECIST

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1

          -  Absolute neutrophil count (ANC) >= 1500/mm^3

          -  Platelet count >= 100,000/mm^3

          -  Hemoglobin > 9.0 g/dL or >= 5.6 mmol/L without transfusion or (EPO) erythropoietin
             dependency (within 7 days of assessment)

          -  Serum total bilirubin =< 1.5 X upper limit of normal (ULN) or direct bilirubin =<
             (ULN) for subjects with total bilirubin levels > 1.5 ULN

          -  Aspartate transaminase (AST) =< 2.5 x ULN or =< 5 x ULN for subjects with liver
             metastases

          -  Albumin >= 2.5mg/dL

          -  International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless
             subject is receiving anticoagulant therapy as long as PT or partial thromboplastin
             time (PTT) is within therapeutic range of intended use of anticoagulants

          -  Activated partial thromboplastin time (aPTT) =< 1.5 ULN unless subject is receiving
             anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use
             of anticoagulants

          -  Creatinine =< 1.5 X upper limit of normal (ULN)

               -  NOTE: measured or calculated (per institutional standard) creatinine clearance is
                  acceptable >= 60 mL/min for subject with creatinine levels > 1.5 X institutional
                  ULN

          -  Negative urine or serum pregnancy test done =< 72 hours prior to first treatment, for
             women of childbearing potential only

               -  If the urine test is positive or cannot be confirmed as negative, a serum
                  pregnancy test will be required

          -  Provide informed written consent

          -  Willing to return to enrolling institution for follow-up

          -  Willing to provide tissue from a newly obtained core or excisional biopsy of a tumor
             lesion in appropriate low risk cutaneous lesions

               -  NOTE: if the tissue biopsy is deemed to be of increased risk for the patient, the
                  biopsy should not be performed and is optional

               -  NOTE: newly-obtained is defined as a specimen obtained up to 42 days prior to
                  registration where no anti-cancer therapy after the specimen was obtained and
                  registration

        Exclusion Criteria:

          -  Any of the following:

               -  Pregnant women

               -  Nursing women

               -  Men or women of childbearing potential who are unwilling to employ adequate
                  contraception

                    -  NOTE: 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; 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; abstain from heterosexual activity is
                       also acceptable method of contraception for males

          -  Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment
             of the investigator, would make the patient inappropriate for entry into this study or
             interfere significantly with the proper assessment of safety and toxicity of the
             prescribed regimens

          -  Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)

          -  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

          -  Receiving any other investigational agent which would be considered as a treatment for
             the primary neoplasm or used an investigational device =< 4 weeks from registration

          -  History of myocardial infarction =< 6 months, or congestive heart failure requiring
             use of ongoing maintenance therapy for life-threatening ventricular arrhythmias

          -  Known history of active TB (Bacillus tuberculosis)

          -  Hypersensitivity to pembrolizumab or any of its excipients

          -  Prior anti-cancer monoclonal antibody (mAb) =< 4 weeks prior to registration or who
             has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents
             administered more than 4 weeks prior to registration

          -  Prior chemotherapy, targeted small molecule therapy, or radiation therapy =< 2 weeks
             prior to registration 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

          -  Known secondary malignancy that has progressed within the last 3 years or requires
             active treatment; exceptions include basal cell carcinoma of the skin or squamous cell
             carcinoma of the skin that has undergone potentially curative therapy or in situ
             cervical cancer

          -  Known central nervous system (CNS) metastases and/or carcinomatous meningitis

          -  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

          -  History of (non-infectious) pneumonitis that required steroids or current pneumonitis

          -  Active infection requiring systemic therapy

          -  History or current evidence of any condition, therapy, or laboratory abnormality that
             might confound the results of the trial, interfere with the subject?s participation
             for the full duration of the trial, or is not in the best interest of the subject to
             participate, in the opinion of the treating investigator

          -  Known psychiatric or substance abuse disorders that would interfere with cooperation
             with the requirements of the trial

          -  Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent

          -  Known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or
             hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is
             detected)

          -  Received a live vaccine =< 30 days prior to registration

               -  Note: seasonal influenza vaccines for injection are generally inactivated flu
                  vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist)
                  are live attenuated vaccines, and are not allowed
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Duration of response
Time Frame:From registration to disease progression, assessed up to 2 years
Safety Issue:
Description:Will be estimated using the Kaplan-Meier method.

Secondary Outcome Measures

Measure:Biomarker changes during treatment
Time Frame:Baseline up to 12 weeks
Safety Issue:
Description:For each patient and each biomarker, a times-series plot of biomarker value will be constructed. These graphs will be visually examined for trends within and between the group of patients whose tumor responded to treatment and the group of patients whose tumor did not respond to treatment. Will include assessing total tumor RNA through RNA seq and PDL1 expression through the use of immunohistochemistry.

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Mayo Clinic

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