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Neoantigen Vaccine Plus Locally Administered Ipilimumab and Systemic Nivolumab in Advanced Melanoma

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ClinicalTrials.gov Identifier: NCT03929029
Recruitment Status : Not yet recruiting
First Posted : April 26, 2019
Last Update Posted : July 17, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Patrick Ott, MD, Dana-Farber Cancer Institute

Brief Summary:

This research study is studying a new type of personalized neoantigen vaccine (NeoVax) plus Montanide® in combination with Ipilimumab (Yervoy™) and Nivolumab (Opdivo®) as a possible treatment for melanoma.

The drugs involved in this study are:

  • Personalized Neoantigen Vaccine
  • Poly-ICLC (Hiltonol®)
  • Montanide®
  • Ipilimumab (Yervoy™)
  • Nivolumab (Opdivo®)

Condition or disease Intervention/treatment Phase
Melanoma Drug: Nivolumab Biological: NeoVax plus Montanide Drug: Ipilimumab Phase 1

  Show Detailed Description

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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 Ib Study of Neoantigen Vaccine (NeoVax Plus Montanide) in Combination With Nivolumab and Locally Administered Ipilimumab in Patients With Advanced Melanoma
Estimated Study Start Date : November 1, 2019
Estimated Primary Completion Date : March 31, 2021
Estimated Study Completion Date : September 30, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma

Arm Intervention/treatment
Experimental: Nivolumab+Ipilimumab+NeoVax plus Montanide
  • Run in period will begin within 2 weeks of metastatic tissue biopsy, once the following criteria
  • Patients will receive Nivolumab at a flat dose I.V. infusion every 4 weeks (28 days)
  • Patients will receive Ipilimumab injection on weeks 12, 15, 18, and 21
  • Patients will receive NeoVax plus Montanide injection on weeks 12, 15, 18, and 21
Drug: Nivolumab
Nivolumab is an antibody that prevent cancer cells from suppressing the immune response so that the body can attack and kill the cancer
Other Name: Opdivo

Biological: NeoVax plus Montanide
Montanide® is an activator of immunity that enhances response to vaccination through slow release of the peptides from the injection site and its ability to create an inflammation and stimulate the recruitment of specific cells of your immune system. Montanide® will be mixed with the personalized neoantigen vaccine

Drug: Ipilimumab
Ipilimumab is an antibody that prevent cancer cells from suppressing the immune response so that the body can attack and kill the cancer
Other Name: Yervoy




Primary Outcome Measures :
  1. Rate of DLT [ Time Frame: 7 weeks ]
    Assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0


Secondary Outcome Measures :
  1. Assess the induction of IFN-γ T-cell response or tetramer staining to the assay peptides [ Time Frame: 16 weeks ]
    The proportion of patients who achieve more than 55 SFU/106 PBMC or 3 times their baseline level

  2. Rate of objective responses [ Time Frame: 24 weeks ]
    Assessed by RECIST1.1

  3. Rate of participants with clinical benefit [ Time Frame: 24 weeks ]
    Assessed by RECIST1.1

  4. Rate of participants with response conversion [ Time Frame: 24 weeks ]
    Assessed by RECIST1.1

  5. Rate of complete responses [ Time Frame: 24 weeks ]
    Assessed by RECIST1.1

  6. Rate of partial responses [ Time Frame: 24 weeks ]
    Assessed by RECIST1.1

  7. Rate of participants with progressive disease [ Time Frame: 24 weeks ]
    Assessed by RECIST1.1

  8. Rate of participants with stable disease [ Time Frame: 24 weeks ]
    Assessed 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:

  • Participant is willing and able to give written informed consent
  • Participants must have histologically confirmed melanoma that is unresectable stage III or stage IV; at least one site of disease must be resectable, partially-resectable, or amenable to core biopsies to provide tumor tissue for sequence analysis
  • Participants must have measurable disease by RECIST v1.1 that has not been treated with local therapy within the last 12 months of study treatment. The measurable lesion and the lesion used for surgical or core biopsies can be identical as long as it remains measurable after biopsy
  • Age ≥ 18 years
  • ECOG performance status of 0 or 1
  • Recovered from all toxicities associated with prior treatment, to acceptable baseline status (as to Lab toxicity see below limits for inclusion) or a National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4, Grade of 0 or 1, except for toxicities not considered a safety risk, such as alopecia or vitiligo
  • Participants must have normal organ and marrow function as defined below:

    • WBC ≥3,000/µL
    • ANC ≥1,500/µL
    • Platelets ≥100,000/µL
    • Hemoglobin ˃ 9.0 g/dL
    • Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
    • AST(SGOT)/ALT(SGPT) ≤ 3 x ULN
    • Creatinine ≤ 1.5 x ULN OR
    • Creatinine clearance ≥40 mL/min/1.73 m2 for participants with creatinine levels above institutional normal (if using the Cockcroft-Gault formula below):
    • Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL
    • Male CrCl = (140 - age in years) x weight in kg x 1.00 72 x serum creatinine in mg/dL
  • Women of childbearing potential (WOCBP) should have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of Nivolumab, because the effects of NeoVax plus Montanide and Nivolumab on the developing human fetus are unknown
  • Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with study agents, breastfeeding should be discontinued if the mother is treated with Ipilimumab, Nivolumab and Personalized Neoantigen vaccine + Montanide.
  • Female participants enrolled in the study, who are not free from menses for >2 years, post hysterectomy / oophorectomy, or surgically sterilized, should 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 23 weeks (30 days plus the time required for Nivolumab to undergo five half-lives) 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. 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 participants should agree to use an adequate method of contraception starting with visit 1 through 31 weeks after the last dose of study therapy
  • Eligibility Criteria for Secondary Registration
  • ECOG performance status of 0 or 1
  • Screening laboratory values must meet the following criteria and should be obtained within 7 days prior to registration

    • WBC ≥ 3000/μL
    • Neutrophils ≥ 1500/μL
    • Platelets ≥ 100 x103/μL
    • Hemoglobin > 9.0 g/dL
    • Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min (if using the Cockcroft-Gault formula below):
    • Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL
    • Male CrCl = (140 - age in years) x weight in kg x 1.00 72 serum creatinine in mg/dL
    • AST/ALT ≤ 3 x ULN
    • Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
  • Women of childbearing potential (WOCBP) should have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of Nivolumab, because the effects of NeoVax plus Montanide and Nivolumab on the developing human fetus are unknown
  • Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with study agents, breastfeeding should be discontinued if the mother is treated with Ipilimumab, Nivolumab and Personalized Neoantigen vaccine + Montanide.
  • Female participants enrolled in the study, who are not free from menses for >2 years, post hysterectomy / oophorectomy, or surgically sterilized, should 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 23 weeks (30 days plus the time required for Nivolumab to undergo five half-lives) 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 participants should agree to use an adequate method of contraception starting with visit 1 through 31 weeks after the last dose of study therapy

Exclusion Criteria:

  • Prior immunotherapy for metastatic melanoma except anti-CTLA-4
  • Concomitant therapy with any anti-cancer agents, other investigational anti-cancer therapies, or immunosuppressive agents including but not limited to methotrexate, chloroquine, azathioprine, etc. within six months of study participation
  • Active brain metastases or leptomeningeal metastases
  • Use of a non-oncology vaccine therapy for prevention of infectious diseases during the 4 week period prior to first dose of Nivolumab. Participants may not receive any non-oncology vaccine therapy during the period of Nivolumab or NeoVax plus Montanide 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
  • Active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
  • A condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
  • test positive for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection
  • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
  • Uncontrolled intercurrent illness including, but not limited to ongoing or active infection requiring treatment, symptomatic
  • 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 AEs
  • Planned major surgery
  • Pregnant women are excluded from this study because Nivolumab, 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 Nivolumab, personalized neoantigen peptides and poly-ICLC, nursing women are excluded from this study
  • Individuals with a history of an 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 3 years and are deemed by the investigator to be at low risk for recurrence of that malignancy; b) individuals with the following cancers are eligible if diagnosed and treated - carcinoma in situ of the breast, oral cavity or cervix, localized prostate cancer, 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): NCT03929029


Contacts
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Contact: Patrick A Ott, MD 617-632-3000 patrick_ott@dfci.harvard.edu

Locations
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United States, Massachusetts
Dana Farber Cancer Institute Not yet recruiting
Boston, Massachusetts, United States, 02215
Contact: Patrick A Ott, MD    617-632-3000    patrick_ott@dfci.harvard.edu   
Principal Investigator: Patrick A Ott, MD         
Sponsors and Collaborators
Dana-Farber Cancer Institute
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Patrick A Ott, MD Dana-Farber Cancer Institute

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Responsible Party: Patrick Ott, MD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT03929029     History of Changes
Other Study ID Numbers: 18-279
1R01CA229261 ( U.S. NIH Grant/Contract )
First Posted: April 26, 2019    Key Record Dates
Last Update Posted: July 17, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor- Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: Data can be shared no earlier than 1 year following the date of publication.
Access Criteria: Requests may be directed to: [contact information for Sponsor- Investigator or designee].

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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:
Melanoma

Additional relevant MeSH terms:
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Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Vaccines
Nivolumab
Ipilimumab
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological
Antineoplastic Agents