Clinical Trials /

Personalized Immunotherapy in Adults With Advanced Cancers Immunotherapy in Adults With Advanced Cancers

NCT03568058

Description:

The purpose of this study is to determine if it is possible to make and administer safely a 'personalized' vaccine to treat patients that have been diagnosed with advanced cancer and are not candidates for curative therapy.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Personalized Immunotherapy in Adults With Advanced Cancers Immunotherapy in Adults With Advanced Cancers
  • Official Title: A Phase 1b Safety and Feasibility Study of Personalized Immunotherapy in Adults With Advanced Cancers

Clinical Trial IDs

  • ORG STUDY ID: 180410
  • NCT ID: NCT03568058

Conditions

  • Advanced Cancer

Interventions

DrugSynonymsArms
personalized vaccineanti-PD1 and vaccine
Pembrolizumabkeytrudaanti-PD1 and vaccine

Purpose

The purpose of this study is to determine if it is possible to make and administer safely a 'personalized' vaccine to treat patients that have been diagnosed with advanced cancer and are not candidates for curative therapy.

Detailed Description

      The purpose of this study is to determine if it is possible to make and administer safely a
      'personalized' vaccine to treat patients that have been diagnosed with advanced cancer and
      are not candidates for curative therapy.

      This 'personalized' vaccine will use information gained from specific characteristics of your
      own cancer. It is known that cancer has mutations (changes in genetic material) that are
      specific to an individual and tumor. These mutations can cause the tumor cells to produce
      proteins that appear very different from the body's own cells. It is possible that these
      proteins used in a vaccine may induce strong immune (protective) responses, which may help
      your body fight any tumor cells that could cause your cancer to come back in the future. The
      study will examine the safety of the vaccine when given at several time points and will
      examine your blood cells for signs that the vaccine induced an immune response.

      The personalized vaccine will be given in combination with an anti-PD1 antibody,
      pembrolizumab, which is used with the intention to increase anti-cancer immunity
      (protection). Pembrolizumab is a type of drug that blocks certain proteins made by some types
      of immune system cells, such as T cells, and some cancer cells. These proteins help keep
      immune responses in check and can keep T cells from killing cancer cells. When these proteins
      are blocked, the "brakes" on the immune system are released and T cells are able to kill
      cancer cells better.

      This personalized vaccine is considered experimental because this is not an FDA approved
      therapy for cancer.

      Pembrolizumab is FDA approved for the treatment of melanoma, non-small cell lung cancer
      (NSCLC), head and neck squamous cell carcinoma (HNSCC), classical Hodgkin lymphoma (cHL),
      urothelial carcinoma, microsatellite instability-high cancer (MSI-H), gastric cancer,
      cervical cancer, and hepatocellular carcinoma (HCC). Pembrolizumab is considered experimental
      (investigational) for the treatment of all other cancer types.
    

Trial Arms

NameTypeDescriptionInterventions
vaccine and anti-PD-1Experimentalpersonalized vaccine and anti-PD-1 administered concurrently at the start of study therapy
  • personalized vaccine
  • Pembrolizumab
anti-PD1 before vaccineExperimentalanti-PD-1 antibody for 6 weeks followed by personalized vaccine therapy
  • personalized vaccine
  • Pembrolizumab
anti-PD1 and vaccineExperimentalanti-PD-1 antibody followed by personalized vaccine therapy
  • personalized vaccine
  • Pembrolizumab
vaccineExperimentalpersonalized vaccine therapy
  • personalized vaccine

Eligibility Criteria

        Inclusion Criteria

          -  Histologically or cytologically documented incurable solid tumor [excluding lymphoma].

          -  Measurable disease as defined by RECIST 1.1

          -  Progressed on or be intolerant to therapies that are known to provide clinical
             benefit.

          -  Non-measurable disease by RECIST 1.1 and high-risk (>50% over 5 years) of mortality

          -  At least one tumor site accessible for biopsy.

          -  Adequate organ function

          -  Women of child-bearing potential and men with partners of child-bearing potential must
             agree to use adequate contraception (hormonal or barrier method of birth control;
             abstinence) prior to study entry, for the duration of study participation, and for 90
             days following completion of therapy.

        Exclusion Criteria

          -  Currently receiving or has received another anti-cancer therapy within 4 weeks prior
             to first dose of vaccine study treatment.

          -  Currently receiving or has received PD1/PDL1 inhibitor immunotherapy within 4 weeks
             prior to first dose of study treatment.

          -  Currently receiving or has received anti-PD1 or anti-CTLA4 treatment during the
             vaccine preparation period.

          -  Receiving TNF pathway inhibitors, PI3 kinase inhibitors, systemic steroid therapy or
             any other form of immunosuppressive therapy within 14 days prior to the first dose of
             study medication.

          -  Received an investigational agent within 28 days prior to the first dose of study
             drug.

          -  Untreated brain metastases; individuals with treated and stable metastases are
             eligible. Eligible subjects should have recovered from the acute effects of radiation
             therapy or surgery prior to study entry, have discontinued corticosteroid treatment
             for brain metastases for at least 4 weeks and are neurologically stable for 8 weeks
             (confirmed by MRI) prior to administration of experimental therapy

          -  Has known history of Human Immunodeficiency Virus (HIV).

          -  Received a diagnosis of hepatitis B or hepatitis C for which there is no clear
             evidence of natural immunity, immunity subsequent to vaccination, or successful
             eradication of the virus following antiviral therapy (individuals who are hepatitis C
             antibody positive may be enrolled if negative viral load confirmed).

          -  History of autoimmune disease including: inflammatory bowel disease (including
             ulcerative colitis and Crohn's Disease), rheumatoid arthritis, systemic progressive
             sclerosis (scleroderma), systemic lupus erythematosus, autoimmune vasculitis (e.g.
             Wegener's granulomatosis); central nervous system or motor neuropathy considered of
             autoimmune origin (e.g. Guillain-Barré syndrome, myasthenia gravis, multiple
             sclerosis). Individuals with vitiligo, Sjogren's Syndrome, interstitial cystitis,
             Graves' or Hashimoto's Disease, celiac disease, DM1, or hypothyroidism stable on
             hormone replacement will be allowed with Study Medical Monitor's approval.

          -  Has a history of (non-infectious) pneumonitis that required steroids or has current
             pneumonitis.

          -  History of receiving a solid organ transplant or allogeneic bone marrow transplant.

          -  Major surgical procedure within 28 days prior to the first dose of study drug.

          -  If female, pregnant or breastfeeding.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Quantitative frequency of TCR
Time Frame:1 year
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Overall Response
Time Frame:1 year
Safety Issue:
Description:RECIST 1.1
Measure:Progression-free survival (PFS)
Time Frame:1 year
Safety Issue:
Description:Duration of time from start of study treatment until objective tumor progression or death.
Measure:Time to Progression
Time Frame:1 year
Safety Issue:
Description:Duration of time from start of study treatment until objective tumor progression.
Measure:Overall Survival
Time Frame:1 year
Safety Issue:
Description:Duration of time from start of study treatment to death

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Ezra Cohen

Trial Keywords

  • immunotherapy
  • personalized cancer vaccine
  • personalized immunotherapy
  • pembrolizumab
  • Keytruda
  • cancer
  • neoantigen
  • solid tumor
  • vaccine

Last Updated

January 3, 2020