Clinical Trials /

A Study Combining NeoVax, a Personalized NeoAntigen Cancer Vaccine, With Ipilimumab to Treat High-risk Renal Cell Carcinoma

NCT02950766

Description:

This research study is evaluating a new type of Kidney Cancer vaccine called "Personalized NeoAntigen Cancer Vaccine"as a possible treatment for Kidney Cancer. The following intervention will be involved in this study: - Personalized Neoantigen Vaccine - Poly-ICLC (Hiltonol) - Ipilimumab

Related Conditions:
  • Clear Cell Renal Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study Combining NeoVax, a Personalized NeoAntigen Cancer Vaccine, With Ipilimumab to Treat High-risk Renal Cell Carcinoma
  • Official Title: A Phase I Study Combining NeoVax, a Personalized NeoAntigen Cancer Vaccine, With Ipilimumab to Treat High-risk Renal Cell Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: 16-097
  • NCT ID: NCT02950766

Conditions

  • Kidney Cancer

Interventions

DrugSynonymsArms
NeoVaxneoantigen vaccineNeovax in Combination with Ipilimumab
IpilimumabYervoyNeovax in Combination with Ipilimumab

Purpose

This research study is evaluating a new type of Kidney Cancer vaccine called "Personalized NeoAntigen Cancer Vaccine"as a possible treatment for Kidney Cancer. The following intervention will be involved in this study: - Personalized Neoantigen Vaccine - Poly-ICLC (Hiltonol) - Ipilimumab

Detailed Description

      This research study is a Phase I clinical trial, which tests the safety of an
      investigational kidney cancer vaccine and also tries to define the appropriate dose of the
      investigational kidney cancer vaccine to use for further studies. "Investigational" means
      that the kidney cancer vaccine, in this case the Personalized Neoantigen Cancer Vaccine, is
      being studied. It also means that the FDA (the U.S. Food and Drug Administration) has not
      approved the Personalized Cancer Vaccine for any use in patients, including people with
      kidney cancer.

      Poly-ICLC (also called Hiltonol) is an experimental "viral mimic" and an activator of
      immunity. Poly-ICLC is an investigational drug, meaning the FDA has not approved it as a
      treatment for any disease.

      Personalized NeoAntigen Cancer Vaccine: The purpose of this study is to determine if it is
      possible to make and administer safely a vaccine against kidney cancer by using information
      gained from specific characteristics of the participant's own kidney cancer. It is known
      that kidney cancers have mutations (changes in genetic material) that are specific to an
      individual patient 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 responses, which may help the participant's body
      fight any tumor cells that could cause the kidney cancer to come back in the future. The
      study will examine the safety of the vaccine when given at several different time points and
      will examine the participant's blood cells for signs that the vaccine induced an immune
      response.

      Ipilimumab (Yervoy™) is an antibody that has been approved by the United States Food and
      Drug Administration (FDA) for the treatment of melanoma.

      In this research study, the investigators are looking at the safety and tolerability of the
      Personalized NeoAntigen Cancer Vaccine combined with Ipilimumab as well as the body's immune
      response to the vaccine. Ipilimumab will be delivered as an injection given underneath the
      skin rather than injected in the vein in proximity to each vaccination site in order to 1)
      direct anti-CTLA4 activity to the vaccine-draining lymph nodes and 2) limit potential toxic
      effects.
    

Trial Arms

NameTypeDescriptionInterventions
Neovax in Combination with IpilimumabExperimentalPatients will undergo surgery with the intent to resect the primary kidney tumor Neovax is a combination of Poly-ICLC and Neoantigen Peptides Priming doses of NeoVax will be administered on days 1, 4, 8, 15, and 22 In the boost phase, vaccine will be administered on days 78 (week 12) and 134 (week 20 Ipilimumab will be injected within 1 cm of each NeoVax administration
  • NeoVax
  • Ipilimumab

Eligibility Criteria

        Inclusion Criteria:

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

          -  Patient is agreeable to allow tumor and normal tissue samples to be submitted for
             complete exome and transcriptome sequencing.

          -  Patients must have histologically confirmed renal cell carcinoma, stage III or IV
             before starting study drugs per AJCC (American Joint Committee on Cancer) 7th edition
             7. Patients undergoing a potentially curative metastasectomy are eligible if the
             tissue from the surgery is enough to make a vaccine. Patients who are asymptomatic
             from their disease and with low volume metastatic disease (5 lesions or less, all
             <2cm) are eligible.

               -  Patients with clear cell and non-clear cell histology are allowed.

               -  Patient should sign the consent before their planned surgery.

               -  Patients who have sarcomatoid elements in addition to having renal cell
                  carcinoma (RCC) are allowed.

          -  ECOG (Eastern Cooperative Oncology Group) performance status ≤ 1

          -  Age ≥ 18 years.

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

               -  leukocytes ≥3,000/mcL (microliter)

               -  absolute neutrophil count ≥1,500/mcL

               -  platelets ≥100,000/mcL

               -  total bilirubin within normal institutional limits

               -  AST (aspartate aminotransferase)(SGOT) /ALT (alanine aminotransferase)(SGPT)
                  ≤2.5 × institutional upper limit of normal

               -  creatinine ≤ 1.6 mg/dL OR

               -  creatinine clearance ≥50 mL/min/1.73 m2 for participants with creatinine levels
                  above institutional normal.

          -  Women of childbearing potential (WOCBP) must have a negative pregnancy test (minimum
             sensitivity 25 IU/L or equivalent of HCG) before entry onto the trial and within 7
             days prior to start of study medication, because the effects NeoVax on the developing
             human fetus are unknown. It is the investigators' responsibility to repeat the
             pregnancy test should start of treatment be delayed.

          -  Female patients enrolled in the study, who are not free from menses for >2 years,
             post hysterectomy / oophorectomy, or surgically sterilized, must be willing to use
             either 2 adequate barrier methods or a barrier method plus a hormonal method of
             contraception to prevent pregnancy or to abstain from sexual activity for the
             duration of treatment with ipilimumab plus 5 half-lives of ipilimumab (75 days) plus
             30 days (duration of ovulatory cycle) for a total of 105 days post-treatment
             completion. Approved contraceptive methods include for example: intra uterine device,
             diaphragm with spermicide, cervical cap with spermicide, male condoms, or female
             condom with spermicide. Spermicides alone are not an acceptable method of
             contraception.

          -  Male patients must agree to use an adequate method of contraception for the duration
             of treatment with study drugs plus 5 half-lives of the study drug (75 days) plus 90
             days (duration of sperm turnover) for a total of 165 days post-treatment

        Eligibility Criteria for Secondary Registration

          -  ECOG performance status <1

          -  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 within normal institutional limits

               -  AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal

               -  creatinine ≤ 1.6 mg/dL OR

               -  creatinine clearance ≥50 mL/min/1.73 m2 for participants with creatinine levels
                  above institutional normal.

          -  Women of childbearing potential (WOCBP) must have a negative pregnancy test (minimum
             sensitivity 25 IU/L or equivalent of HCG) within 7 days prior to start of study
             medication, because the effects NeoVax on the developing human fetus are unknown. It
             is the investigators' responsibility to repeat the pregnancy test should start of
             treatment be delayed.

          -  Female patients enrolled in the study, who are not free from menses for >2 years,
             post hysterectomy / oophorectomy, or surgically sterilized, must be willing to use
             either 2 adequate barrier methods or a barrier method plus a hormonal method of
             contraception to prevent pregnancy or to abstain from sexual activity throughout the
             study, starting with visit 1 through 4 weeks after the last dose of study therapy.
             Approved contraceptive methods include for example; intra uterine device, diaphragm
             with spermicide, cervical cap with spermicide, male condoms, or female condom with
             spermicide. Spermicides alone are not an acceptable method of contraception.

          -  Male patients must agree to use an adequate method of contraception for the duration
             of treatment with study drugs plus 5 half-lives of the study drug (75 days) plus 90
             days (duration of sperm turnover) for a total of 165 days post-treatment

        Exclusion Criteria:

          -  Prior treatment with immune-modulatory agents including, but not limited to: IL-2
             (interleukin-2), CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) blockade, PD-1
             (Programmed cell death protein 1) /PD-L1 (Programmed cell death protein ligand 1)
             blockade, CD40 (cluster of differentiation 40) stimulation, or CD137 (tumor necrosis
             factor receptor superfamily member 9) stimulation.

          -  Prior investigational ccRCC-directed cancer vaccine therapy.

          -  Patients with active brain metastases or leptomeningeal disease.

          -  Prior systemic therapy, including targeted therapy such as VEGF (vascular endothelial
             growth factor) or mTOR (mammilian target of rapamycin) inhibitors unless it is >6
             months between last dose of drug and first vaccination with NeoVax

          -  Treatment with other investigational products within the last 2 months prior to entry
             into this study.

          -  Previous bone marrow or stem cell transplant.

          -  Concomitant therapy with any anti-cancer agents, other investigational anti-cancer
             therapies, or immunosuppressive agents; chronic use of systemic corticosteroids with
             prednisone >10 mg/day.

          -  Use of a non-oncology vaccine therapy for prevention of infectious diseases during
             the four week period prior to enrollment to the study. Patients may not receive any
             non-oncology vaccine therapy during the period of NeoVax administration and until at
             least 8 weeks after the last dose of study therapy

          -  History of severe allergic reactions attributed to any vaccine therapy for the
             prevention of infectious diseases

          -  History of or current active autoimmune diseases, [e.g. including but not limited to
             inflammatory bowel diseases (IBD), rheumatoid arthritis, autoimmune thyroiditis,
             autoimmune hepatitis, systemic sclerosis (scleroderma and variants), systemic lupus
             erythematosus, autoimmune vasculitis, autoimmune neuropathies (such as Guillain-Barre
             syndrome). Vitiligo and adequately controlled endocrine deficiencies such as
             hypothyroidism are not exclusionary.].

          -  Patients who have had a history of acute diverticulitis, intra-abdominal abscess, GI
             obstruction and abdominal carcinomatosis which are known risk factors for bowel
             perforation.

          -  Concomitant treatment with corticosteroids greater than physiologic doses (used in
             the management of cancer or non-cancer-related illnesses). Topical (if not including
             the proposed vaccination sites) or inhalational steroids are allowed.

          -  Known chronic infections with HIV, hepatitis B or C.

          -  Uncontrolled intercurrent illness including, but not limited to ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia.

          -  History of current immunodeficiency disease [e.g., splenectomy or splenic
             irradiation].

          -  Any underlying medical condition, psychiatric condition or social situation that in
             the opinion of the investigator would compromise study administration as per protocol
             or compromise the assessment of adverse events (AEs).

          -  Pregnant women are excluded from this study because personalized neoantigen peptides
             and poly-ICLC are agents with unknown risks to the developing fetus. Because there is
             an unknown but potential risk of adverse events in nursing infants secondary to
             treatment of the mother with personalized neoantigen peptides and poly-ICLC, nursing
             women are excluded from this study.

          -  Individuals with a history of another invasive malignancy are ineligible except for
             the following circumstances: a) individuals with a history of invasive malignancy are
             eligible if they have been disease-free for at least 2 years and are deemed by the
             investigator to be at low risk for recurrence of that malignancy; b) individuals with
             any of the following cancers are eligible if diagnosed and treated: carcinoma in situ
             of the breast, oral cavity or cervix and basal cell or squamous cell carcinoma of the
             skin.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with dose-limiting toxicity (DLT) experienced within 49 days (7 weeks) of treatment initiation as assessed by CTCAE v4.0
Time Frame:49 days
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Number of participants with NeoVax induced IFN γ (interferon γ) T-cell Response against neoepitopes measured by ELISPOT at week 16
Time Frame:16 weeks
Safety Issue:
Description:
Measure:Number of participants alive at 2 years
Time Frame:2 years
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • Kidney Cancer

Last Updated

October 28, 2016