Clinical Trials /

Phase 1-2 Study of ADXS11-001 or MEDI4736 Alone or Combo In Cervical or HPV+ Head & Neck Cancer

NCT02291055

Description:

Part A: (ADXS11-001 + MEDI4736 Combination Therapy) will determine the safety and tolerability of the combination and to identify a RP2D. Part B: Phase 2 design which will randomize subjects 1:1 to either MEDI4736 alone or MEDI4736+ADXS11-001 in subjects who have failed at least 1 prior systemic treatment for their recurrent/persistent or metastatic cervical cancer.

Related Conditions:
  • Cervical Carcinoma
  • Head and Neck Squamous Cell Carcinoma
Recruiting Status:

Suspended

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Phase 1-2 Study of ADXS11-001 or MEDI4736 Alone or Combo In Cervical or HPV+ Head & Neck Cancer

Title

  • Brief Title: Phase 1-2 Study of ADXS11-001 or MEDI4736 Alone or Combo In Cervical or HPV+ Head & Neck Cancer
  • Official Title: Phase 1-2 Study of ADXS11-001 or MEDI4736 Alone or Combination In Previously Treated Locally Advanced or Metastatic Cervical or HPV+ Head & Neck Cancer
  • Clinical Trial IDs

    NCT ID: NCT02291055

    ORG ID: ADXS001-04

    Trial Conditions

    Cervical Cancer

    Cancer

    Head and Neck Cancer

    Trial Interventions

    Drug Synonyms Arms
    ADXS11-001 Arm A, Arm C
    Medi4736 Arm B, Arm C

    Trial Purpose

    Phase 1 (ADXS11-001 + MEDI4736 Combination Therapy) Phase 1 will be a dose-confirmation
    safety run-in of ADXS11-001 and MEDI4736 combination therapy.

    Mandatory fresh biopsies will be obtained pre- and during treatment.

    Phase 2:

    48 subjects will be randomized 1:1:2 to receive ADXS11-001 monotherapy, MEDI4736 monotherapy
    or ADXS11 001 + MEDI4736 combination therapy.

    Arm A: ADXS11-001 Monotherapy:

    Arm B: MEDI4736 Monotherapy:

    Arm C: ADXS11-001 + MEDI4736 combination therapy

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Arm A Experimental ADXS11-001, IV Infusion ADXS11-001
    Arm B Experimental Medi4736, IV Infusion Medi4736
    Arm C Experimental ADXS11-001 & Medi4736, IV Infusion ADXS11-001, Medi4736

    Eligibility Criteria

    Inclusion Criteria:

    1. Be willing and able to provide written informed consent for the trial 2. Be 18 years
    of age on day of signing informed consent 3. Have histologically diagnosis of squamous
    cell cancer of the head & neck with confirmation of HPV positivity or squamous,
    non-squamous, adenosquamous, carcinoma or adenocarcinoma of the cervix which HPV
    positivity is not required 5. Have measurable and/or evaluable disease by RECIST 1.1 6.
    Have ECOG performance status of 0 or 1 7. Have adequate organ function defined by the
    protocol.: 8. Female subjects of childbearing potential (not surgically sterilized or not
    free from menses for > 1 year): must have a negative urine or serum pregnancy test results
    within 72 hours prior to first dose and must be willing to use 2 methods of birth control
    through 120 days after the last dose of study treatment.

    9. Male subjects must agree to use 2 acceptable methods of effective contraception from
    Day 1 thru 120 days after receipt of the final dose of investigational product.

    Exclusion Criteria:

    1. Has not recovered (i.e., Grade 1 or at baseline) from adverse events, with the
    exception of alopecia, due to a previously administered agent.

    2. Has any prior Grade 3 immune-related adverse event (irAE) while receiving
    immunotherapy, including anti-CTLA-4 treatment, or any unresolved irAE >Grade 1.

    3. Has any pulmonary, ocular, or central nervous system (CNS) toxicity while receiving
    prior immunotherapy that has not resolved to <Grade 1.

    4. Requires additional immunosuppression beyond corticosteroids for resolution of
    immune-related AEs.

    5. Is currently participating in or has participated in a study of an investigational
    agent or using an investigational device within 4 weeks of the first dose of
    treatment.

    6. Has a diagnosis of immunodeficiency or is receiving any systemic steroid therapy or
    any other form of immunosuppressive therapy within 7 days prior to Day 1 of trial
    treatment.

    7. Has any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for
    invasive malignancy within 2 years. Concurrent use of hormones for
    non-cancer-related conditions (eg, insulin for diabetes and hormone replacement
    therapy) is acceptable.

    8. Has an active autoimmune disease requiring systemic treatment within the past 3
    months or a documented history of clinically severe autoimmune disease, or a syndrome
    that requires systemic steroids or immunosuppressive agents.

    9. Has evidence of interstitial lung disease or active, non-infectious pneumonitis,
    active or prior documented inflammatory bowel diseases (e.g., Crohn's disease,
    ulcerative colitis)

    10. Has an active infection requiring systemic therapy. Prior to dosing with study
    drug(s), the subject must be at least 5 half lives from their last dose of
    antibiotic.

    11. Has a history or current evidence of any condition, therapy, or laboratory
    abnormality that might confound the results of the trial, interfere with the
    subject's participation for the full duration of the trial, or is not in the best
    interest of the subject to participate, in the opinion of the treating investigator.

    12. Has a history of psychiatric or substance abuse disorders that would interfere with
    cooperation with the requirements of the trial.

    13. Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).

    14. Has known active hepatitis B (e.g., HBsAg reactive) or hepatitis C (e.g., HCV RNA
    [qualitative] is detected).

    15. Has a contraindication to administration of non-steroidal anti-inflammatory drugs
    (NSAIDs).

    16. Has a known allergy to any component of the study drug(s) formulations

    17. Has received a live vaccine within 30 days prior to the first dose of trial
    treatment.

    18. Has a history of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced
    pneumonitis, organizing pneumonia, risk of pulmonary toxicity, or evidence of active
    pneumonitis on screening chest CT scan.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Number of subjects with adverse events in each dose level (Part A)

    Number of subjects with progression free survival (Part B)

    Number of subjects with adverse event in combination dose (Part B)

    Secondary Outcome Measures

    Trial Keywords