Clinical Trials /

Nivolumab and HPV-16 Vaccination in Patients With HPV-16 Positive Incurable Solid Tumors

NCT02426892

Description:

The goal of this clinical research study is to learn if nivolumab combined with ISA101 can help to control cancer that has spread. The safety of the study drugs will also be studied. This is an investigational study. ISA101 is not FDA approved or commercially available. It is currently being used for research purposes only. Nivolumab is FDA approved to treat certain types of melanoma in patients who no longer respond to other drugs. Combining ISA101 with nivolumab is investigational. The study doctor can explain how the study drugs are designed to work. Up to 28 participants will be enrolled in this study. All will take part at MD Anderson.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Nivolumab</span> and HPV-16 Vaccination in Patients With HPV-16 Positive Incurable Solid Tumors

Title

  • Brief Title: Nivolumab and HPV-16 Vaccination in Patients With HPV-16 Positive Incurable Solid Tumors
  • Official Title: Phase II Trial of Nivolumab and HPV-16 Vaccination in Patients With HPV-16-Positive Incurable Solid Tumors
  • Clinical Trial IDs

    NCT ID: NCT02426892

    ORG ID: 2014-1047

    NCI ID: NCI-2015-01004

    Trial Conditions

    Solid Tumors

    Trial Interventions

    Drug Synonyms Arms
    Nivolumab BMS-936558, Opdivo ISA101 + Nivolumab

    Trial Purpose

    The goal of this clinical research study is to learn if nivolumab combined with ISA101 can
    help to control cancer that has spread. The safety of the study drugs will also be studied.

    Detailed Description

    Study Drug Administration:

    There are 3 weeks in Cycle 1 and 2 weeks in Cycles 2 and beyond.

    If participant is found to be eligible to take part in this study, they will receive ISA101
    by injection on Day 1 of Cycles 1, 2, and 4. Participant will be closely watched for the
    first 3 hours after each dose in order to check for any allergic reactions. Each time,
    participant will receive 2 injections. One may be in participant's arm and one in their leg.

    Participant will receive nivolumab by vein over 60 minutes on Day 8 of Cycle 1 and Day 1 of
    Cycles 2 and beyond.

    Study Visits:

    On Days 1 and 8 of Cycle 1 and Day 1 of every cycle after that:

    - Participant will have a physical exam.

    - Blood (about 4 teaspoons) will be drawn for routine tests.

    On Day 1 of Cycle 1 and then 1 time a month after that, if participant can become pregnant,
    blood (about 1 teaspoon) or urine will be collected for a pregnancy test.

    At Week 11 and every 6 weeks after that, participant will have a CT scan or MRI to check the
    status of the disease.

    Additional Research Tests:

    Blood (up to 4 teaspoons each time) will be drawn before participant begins to receive the
    study treatment, before they receive ISA101 at Weeks 3 and 7, before they receive nivolumab
    at Weeks 9 and 11, then every 12 weeks after that. These blood samples will be used for
    biomarker tests and tests of the immune system.

    Length of Treatment:

    Participant may take ISA101 for up to 3 doses. Participant may continue taking nivolumab for
    as long as the doctor thinks it is in their best interest. Participant will no longer be
    able to take the study drug if intolerable side effects occur, or if they are unable to
    follow study directions.

    If the disease seems like it has gotten worse, participant may decide to continue to receive
    nivolumab, if they are still eligible. It is possible the study drug may be working even
    though the tumor(s) got larger. However, there are risks of continuing to receive the study
    drug because the disease may actually be getting worse. This is described in the side
    effects section below.

    Patient's participation on the study will be over after the follow-up.

    Follow-up Visits:

    At about 30 days and 70 days after the last study drug dose, and then as often as the doctor
    decides as needed, the following tests and procedures will be performed:

    - Participant will have a physical exam.

    - Blood (about 4 teaspoons) will be drawn for routine tests.

    At about 30 days, 70 days, and every 6 weeks after that (if participant stops the study
    drug[s] for reasons other than the disease getting worse), participant will have a CT or MRI
    scan to check the status of the disease. If the disease gets worse, these scans will stop.

    Every 3 months for up to 3 years after participant's last study drug dose, they will be
    asked how they are doing (either at a visit or by phone). The calls should last about 10
    minutes.

    This is an investigational study. ISA101 is not FDA approved or commercially available. It
    is currently being used for research purposes only. Nivolumab is FDA approved to treat
    certain types of melanoma in patients who no longer respond to other drugs. Combining ISA101
    with nivolumab is investigational. The study doctor can explain how the study drugs are
    designed to work.

    Up to 28 participants will be enrolled in this study. All will take part at MD Anderson.

    Trial Arms

    Name Type Description Interventions
    ISA101 + Nivolumab Experimental HPV-16 vaccination (ISA 101) administered subcutaneously at 100 mcg for a total of 3 doses at 3 to 4 weeks intervals starting on Day 1. Nivolumab administered intravenously at 3 mg/kg every 2 weeks beginning on day 8 after the first vaccine dose. There are 3 weeks in Cycle 1 and 2 weeks in Cycles 2 and beyond. Nivolumab

    Eligibility Criteria

    Inclusion Criteria:

    1. Signed Written Informed Consent: a. Subjects must have signed and dated an IRB/IEC
    approved written informed consent form in accordance with regulatory and
    institutional guidelines. This must be obtained before the performance of any
    protocol related procedures that are not part of normal subject care. b) Subjects
    must be willing and able to comply with scheduled visits, treatment schedule,
    laboratory tests and other requirements of the study.

    2. Target Population: a. Men and women >/= 18 years of age. b. Eastern Cooperative
    Oncology Group (ECOG) performance status of </= 1. c. Subjects with histologically-
    or cytologically-documented incurable Human Papillomavirus (HPV)-16 positive solid
    tumors including oropharyngeal squamous cell carcinoma (OPSCC), cervical, vulvar,
    vaginal, anal, penile cancer. Incurable HPV-16 solid tumors are defined as tumors
    which are not curable by salvage approaches including resection and/or
    re-irradiation. HPV-16 serotype will be assessed by Cervista assay.

    3. Target Population: d. Subjects can be treatment nave for metastatic or incurable
    locally advanced HPV-16 positive solid tumors or can have one prior line of
    treatment.Patients with metastatic /recurrent oropharyngeal/anal/penile HPV-16
    positive carcinomas are eligible upon progression after definitive local treatment
    (usually concurrent chemoradiation) if they are not candidates for salvage surgery or
    re-irradiation. These patients are also eligible after progression on first line
    chemotherapy for recurrent disease. Patients with metastatic /recurrent HPV-16
    positive cervical cancer are eligible after progression on or after chemotherapy
    containing bevacizumab.

    4. Target Population: e. Subjects must have measurable disease by CT or MRI per RECIST
    1.1 criteria; Radiographic Tumor Assessment performed within 28 days of study
    inclusion. f. Target lesions may be located in a previously irradiated field if there
    is documented (radiographic) disease progression in that site. g. Subject entering
    the study will need to consent for mandatory biopsy at study entrance and as an
    optional procedure at week 11 and at progression for biomarker evaluation. Biopsy
    should be excisional, incisional or core needle. Fine needle aspiration is
    insufficient. h. Prior radiotherapy or radiosurgery must have been completed at least
    2 weeks prior to start.

    5. Target Population: i. All baseline laboratory requirements will be assessed and
    should be obtained within -14 days of study registration. Screening laboratory values
    must meet the following criteria: i) WBCs >/= 2000/uL; ii) Neutrophils >/= 1500/uL;
    iii) Platelets >/= 100 x 10^3/uL; iv) Hemoglobin >/= 9.0 g/dL; v) Serum creatinine of
    </= 1.5 X ULN or creatinine clearance > 40 mL/minute (using Cockcroft/Gault formula).
    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; vi) AST </= 1.5X ULN; vii) ALT </= 1.5X ULN; viii) Total bilirubin </= ULN
    (except subjects with Gilbert Syndrome who must have total bilirubin <3.0 mg/dl).

    6. Age and Reproductive Status: a) Women of childbearing potential (WOCBP) must use
    method(s) of contraception for 30 days + 5 half-lives (60 days) of the study drugs.
    For a teratogenic study drug and/or when there is insufficient information to assess
    teratogenicity (preclinical studies have not been done), a highly effective method(s)
    of contraception (failure rate of less than 1% per year) is required. Highly
    effective birth control in this study is defined as a double barrier method. Examples
    include a condom (with spermicide) in combination with a diaphragm, cervical cap, or
    intrauterine device (IUD). The individual methods of contraception should be
    determined in consultation with the investigator. b) WOCBP must have a negative serum
    or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG)
    within 24 hours prior to the start of investigational product.

    7. Age and Reproductive Status: c) Women must not be breastfeeding. d) Men who are
    sexually active with WOCBP must use any contraceptive method with a failure rate of
    less than 1% per year. The investigator shall review contraception methods and the
    time period that contraception must be followed. Men that are sexually active with
    WOCBP must follow instructions for birth control for a period of 90 days plus the
    time required for the investigational drug to undergo 5 half-lives (60 days).

    Exclusion Criteria:

    1. Target Disease Exceptions: a. Subjects with active CNS metastases are excluded.
    Subjects are eligible if CNS metastases are adequately treated and subjects are
    neurologically returned to baseline (except for residual signs or symptoms related to
    the CNS treatment) for at least 2 weeks prior to enrollment. In addition, subjects
    must be either off corticosteroids, or on a stable or decreasing dose of </= 10 mg
    daily prednisone (or equivalent) for 2 weeks. b. Subjects with carcinomatous
    meningitis.

    2. Medical History and Concurrent Diseases: a. Subjects with active, known or suspected
    systemic autoimmune disease. Subjects with vitiligo, type I diabetes mellitus,
    residual hypothyroidism due to autoimmune thyroiditis only requiring hormone
    replacement, or conditions not expected to recur in the absence of an external
    trigger are permitted to enroll. b. Subjects with a condition requiring systemic
    treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other
    immunosuppressive medications within 14 days of start. Inhaled or topical steroids,
    and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are
    permitted in the absence of active autoimmune disease.

    3. Medical History and Concurrent Diseases: c. Prior therapy with anti-PD-1, anti-PD-L1,
    anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody (including ipilimumab or any other
    antibody or drug specifically targeting T-cell co-stimulation or checkpoint
    pathways). d. Subjects with a history of interstitial lung disease. e. Other active
    malignancy requiring concurrent intervention. f. Subjects with previous malignancies
    (except non-melanoma skin cancers, and the following in situ cancers: bladder,
    gastric, colon, endometrial, cervical/dysplasia, melanoma, or breast) are excluded
    unless a complete remission was achieved at least 2 years prior to study entry AND no
    additional therapy is required during the study period.

    4. Medical History and Concurrent Diseases: g. Subjects with toxicities attributed to
    prior anti-cancer therapy other than alopecia and fatigue that have not resolved to
    grade 1 (NCI CTCAE version 4) or baseline before administration of study drug. h.
    Subjects who have not recovered from the effects of major surgery or significant
    traumatic injury at least 14 days before the first dose of study treatment. i.
    Treatment with any investigational agent within 28 days of first administration of
    study treatment.

    5. Physical and Laboratory Test Findings: a) Known history of testing positive for human
    immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). b)
    Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus
    ribonucleic acid (HCV RNA) indicating acute or chronic infection.

    6. Allergies and Adverse Drug Reaction: a) History of severe hypersensitivity reactions
    to other monoclonal antibodies. b) History of allergy or intolerance (unacceptable
    adverse event) to study drugs components.

    7. Sex and Reproductive Status: a) WOCBP who are pregnant or breastfeeding. b) Women
    with a positive pregnancy test at enrollment or prior to administration of study
    medication

    8. Prohibited Treatments and/or Restricted Therapies: a) Ongoing or planned
    administration of anti-cancer therapies other than those specified in this study. b)
    Use of corticosteroids or other immunosuppressive medications as per Exclusion
    Criteria 2b.

    9. Other Exclusion Criteria: a) Any other serious or uncontrolled medical disorder,
    active infection, physical exam finding, laboratory finding, altered mental status,
    or psychiatric condition that, in the opinion of the investigator, would limit a
    subject's ability to comply with the study requirements, substantially increase risk
    to the subject, or impact the interpretability of study results. b) Prisoners or
    subjects who are involuntarily incarcerated. c) Subjects who are compulsorily
    detained for treatment of either a psychiatric or physical (eg, infectious disease)
    illness.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Overall Response Rate (ORR)

    Secondary Outcome Measures

    Trial Keywords

    Solid Tumors

    HPV-16 Positive Incurable Solid Tumors

    ISA101

    HPV-16 vaccination

    Nivolumab

    BMS-936558

    Opdivo