ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02950766
Recruitment Status : Not yet recruiting
First Posted : November 1, 2016
Last Update Posted : August 15, 2018
Sponsor:
Collaborators:
Bristol-Myers Squibb
Oncovir, Inc.
Information provided by (Responsible Party):
Patrick Ott, MD, Dana-Farber Cancer Institute

Brief Summary:

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

Condition or disease Intervention/treatment Phase
Kidney Cancer Drug: NeoVax Drug: Ipilimumab Phase 1

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study Combining NeoVax, a Personalized NeoAntigen Cancer Vaccine, With Ipilimumab to Treat High-risk Renal Cell Carcinoma
Estimated Study Start Date : September 3, 2018
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : September 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Cancer
Drug Information available for: Ipilimumab

Arm Intervention/treatment
Experimental: Neovax in Combination with Ipilimumab

Patients 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

Drug: NeoVax
combination of Neoantigen peptides and poly-ICLC
Other Name: neoantigen vaccine

Drug: Ipilimumab
local administration of ipilimumab
Other Name: Yervoy




Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. 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 ]
  2. Number of participants alive at 2 years [ Time Frame: 2 years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

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): NCT02950766


Contacts
Contact: Patrick Ott, MD 617-632-5456 pott@partners.org
Contact: Toni Choueiri, MD 617-632-5456

Locations
United States, Massachusetts
Beth Israel Deaconess Medical Center Not yet recruiting
Boston, Massachusetts, United States, 02115
Contact: David McDermott, MD    617-632-9285      
Principal Investigator: David McDermott, MD         
Dana Farber Cancer Institute Not yet recruiting
Boston, Massachusetts, United States, 02115
Contact: Patrick Ott, MD, PhD    617-582-9030      
Principal Investigator: Patrick Ott, MD         
Sponsors and Collaborators
Patrick Ott, MD
Bristol-Myers Squibb
Oncovir, Inc.
Investigators
Principal Investigator: Patrick Ott, MD Dana-Farber Cancer Institute
Principal Investigator: Toni Choueiri, MD Dana-Farber Cancer Institute

Responsible Party: Patrick Ott, MD, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT02950766     History of Changes
Other Study ID Numbers: 16-097
First Posted: November 1, 2016    Key Record Dates
Last Update Posted: August 15, 2018
Last Verified: August 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 Patrick Ott, MD, Dana-Farber Cancer Institute:
Kidney Cancer

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Kidney Neoplasms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Vaccines
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs