Clinical Trials /

IRX-2 Regimen and Durvalumab, for Incurable H&N Squamous Cell Carcinoma

NCT03381183

Description:

The purpose of this study is to see if the IRX-2 regimen and Durvalumab, will have a tolerable safety profile and will increase the intratumoral immune profile compared with the pretreatment tumors.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
  • Head and Neck Squamous Cell Carcinoma of Unknown Primary
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: IRX-2 Regimen and Durvalumab, for Incurable H&N Squamous Cell Carcinoma
  • Official Title: A Phase 1b Trial of the IRX-2 Regimen and Durvalumab (MEDI4736), in Patients With Incurable Head and Neck Squamous Cell Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: MCC-19356
  • SECONDARY ID: ESR-16-12571
  • NCT ID: NCT03381183

Conditions

  • Squamous Cell Carcinoma
  • Squamous Cell Carcinoma of the Head and Neck
  • Metastatic Squamous Cell Carcinoma
  • Oral Cavity Squamous Cell Carcinoma
  • Oropharynx Squamous Cell Carcinoma
  • Paranasal Sinus Squamous Cell Carcinoma
  • Hypopharynx Squamous Cell Carcinoma
  • Larynx Squamous Cell Carcinoma

Interventions

DrugSynonymsArms
DurvalumabMEDI4736, IMFINZIPhase 1 - Dose Escalation
IRX-2 RegimenPhase 1 - Dose Escalation

Purpose

The purpose of this study is to see if the IRX-2 regimen and Durvalumab, will have a tolerable safety profile and will increase the intratumoral immune profile compared with the pretreatment tumors.

Detailed Description

      Study Population:

      Patients with histologically or cytologically confirmed recurrent or metastatic squamous cell
      carcinoma of oral cavity, oropharynx, paranasal sinuses, hypopharynx, or larynx that is not
      amenable to local therapy with curative intent. Squamous cell carcinoma of unknown primary in
      cervical lymph node can be included only if p16 status is positive.
    

Trial Arms

NameTypeDescriptionInterventions
Phase 1 - Dose EscalationExperimentalThe dose finding phase of the study will enroll 6 patients at dose level 1. If an unacceptable rate of DLTs is observed, then 6 patients will be enrolled at dose level -1. A DLT will be defined as any Grade 3 or higher toxicity that occurs during the DLT evaluation period and are considered related to IRX-Durva occurred during Cycle 1 Day 1 (= 4 weeks). Toxicity that is clearly and directly related to the primary disease or to another etiology is excluded from this definition.
  • Durvalumab
  • IRX-2 Regimen
Phase 2 - Dose ExpansionExperimental14 patients will be enrolled at the recommended dose level from the dose finding phase for a total enrollment of 20 patients; however, investigators will replace patients with any missing tumor sample collection and continue enrollment until there are at least 20 pre- and post-treatment paired tumors (i.e. minimum 2 of 3 tumors per patient). The 6 patients treated at the recommended dose in the dose finding phase of the study will be counted as a part of the dose expansion patient population,
  • Durvalumab
  • IRX-2 Regimen

Eligibility Criteria

        Inclusion Criteria:

          -  Participants must have histologically or cytologically confirmed squamous cell
             carcinoma of oral cavity, oropharynx, paranasal sinuses, hypopharynx, or larynx.
             Squamous cell carcinoma of unknown primary in cervical lymph node can be included only
             if p16 status is positive.

          -  Must have recurrent or metastatic HNSCC that is not amenable to local therapy with
             curative intent (surgery or radiation therapy with or without chemotherapy).

          -  Willing and able to give informed consent and adhere to protocol therapy; written
             informed consent and any locally required authorization must be obtained from the
             patient prior to performing any protocol-related procedures, including screening
             evaluations

          -  At least 18 years of age

          -  Up to three prior systemic therapy regimens for recurrent and/or metastatic disease.
             Prior exposure to PD-1/PD-L1 inhibitor monotherapy, or prior exposure to IRX-2
             monotherapy is allowed.

          -  Eastern Cooperative Oncology Group (ECOG) 0-2

          -  Adequate normal organ and marrow function as outlined in protocol documentation

          -  Must have measurable disease, defined as at least one lesion that can be accurately
             measured in at least one dimension (longest diameter to be recorded) as outlined in
             Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

          -  Life expectancy of greater than 3 months.

          -  Female participants of childbearing potential must have a negative serum pregnancy
             test within 7 days prior to enrollment.

          -  Body weight must be > 30 Kg.

        Exclusion Criteria:

          -  Prior exposure to a combination of IRX-2 regimen, and PD-1/PD-L1 inhibitors

          -  Radiation therapy with a curable intent within 30 days of first dose of study
             treatment is excluded. However, radiation therapy with a palliative intent is allowed
             to treat after 14 days from the last dose of radiation.

          -  Any medical contraindications or previous therapy that would preclude treatment with
             the IRX-2 Regimen and durvalumab

          -  Any unresolved toxicity NCI Common Terminology Criteria for Adverse Events (CTCAE)
             Grade ≥ 2 from previous anticancer therapy with the exception of alopecia, vitiligo,
             and the laboratory values defined in the inclusion criteria, and except toxicities the
             investigator deems irreversible.

          -  Grade ≥ 2 neuropathy will be evaluated on a case-by-case basis after consultation with
             the study physician

          -  Patients with irreversible toxicity not reasonably expected to be exacerbated by
             treatment with the IRX- regiemtn or durvalumab may be included only after consultation
             with the study physician.

          -  Active or prior documented autoimmune or inflammatory disorders (including
             inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with
             the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome,
             or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid
             arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this
             criterion: Patients with vitiligo or alopecia; Patients with hypothyroidism (e.g.,
             following Hashimoto syndrome) stable on hormone replacement. Any chronic skin
             condition that does not require systemic therapy; Patients without active disease in
             the last 2 years may be included but only after consultation with the study physician;
             Patients with celiac disease controlled by diet alone.

          -  Current or prior use of immunosuppressive medication within 14 days before the first
             dose of durvalumab. The following are exceptions to this criterion: Intranasal,
             inhaled, topical steroid, or local steroid injections (e.g., intra articular
             injection); Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of
             prednisone or its equivalent; Steroids as premedication for hypersensitivity reactions
             (e.g., CT scan premedication).

          -  Major surgical procedure (as defined by the Investigator) within 28 days prior to the
             first dose of durvalumab. Note: Local surgery of isolated lesions for palliative
             intent is acceptable.

          -  History of allogenic organ transplantation.

          -  Symptomatic cardiopulmonary disease (including congestive heart failure and
             hypertension), coronary artery disease, serious arrhythmia or chronic lung disease.
             Patients with these conditions who are stable with relatively minor symptoms and who
             are appropriate candidates for systemic treatments need not be excluded.

          -  Myocardial infarction within the last 3 months.

          -  Known infection with hepatitis B, hepatitis C, or HIV.

          -  Signs or symptoms of systemic bacterial infection (use of antibiotics to treat
             superficial infection or contamination of tumor shall not, by itself, be considered
             evidence of infection).

          -  Clinically significant gastritis or peptic ulcer disease.

          -  Stroke or other symptoms of cerebral vascular insufficiency within the last 3 months.

          -  Allergy to ciprofloxacin (or other quinolones).

          -  Previous diagnosis of invasive cancer from which the individual is not disease-free
             AND that has required treatment within the past 3 years, except for superficial skin,
             cervical cancer in-situ, or early stage prostate or bladder cancer (i.e. treatment
             with curative intent and long term disease-free expectations).

          -  History of leptomeningeal carcinomatosis

          -  Known allergy or hypersensitivity to any of the study drugs or any of the study drug
             excipients.

          -  Females who are pregnant or breastfeeding; males or females of reproductive potential
             who are not willing to employ effective birth control from screening to 90 days after
             the last dose of durvalumab or 1 year after last dose of cyclophosphamide, whichever
             is the longer time period.

          -  Uncontrolled intercurrent illness, including but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
             angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic
             gastrointestinal conditions associated with diarrhea, or psychiatric illness/social
             situations that would limit compliance with study requirement, substantially increase
             risk of incurring AEs or compromise the ability of the patient to give written
             informed consent.

          -  Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms
             calculated from 3 ECGs (within 15 minutes at 5 minutes apart).

          -  History of active primary immunodeficiency

          -  Active infection including tuberculosis (clinical evaluation that includes clinical
             history, physical examination and radiographic findings, and tuberculosis (TB) testing
             in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg)
             result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies).
             Patients with a past or resolved HBV infection (defined as the presence of hepatitis B
             core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for
             hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative
             for HCV RNA.

          -  Receipt of live attenuated vaccine within 30 days prior to the first dose of
             investigational produce (IP). Note: Patients, if enrolled, should not receive live
             vaccine whilst receiving IP and up to 30 days after the last dose of IP.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1 - Maximum Tolerated Dose (MTD)
Time Frame:Up to 6 months
Safety Issue:
Description:MTD of combination of the IRX-2 regimen and durvalumab as outlined in treatment arm.

Secondary Outcome Measures

Measure:Phase 2 - Objective Clinical Response Rate
Time Frame:Up to 12 months post treatment
Safety Issue:
Description:Response to combination of the IRX-2 regimen and durvalumab . Objective response will be documented using standard Response Evaluation in Solid Tumors (RECIST) criteria.
Measure:Phase 2 - Progression-free Survival (PFS)
Time Frame:Up to 6 months post treatment
Safety Issue:
Description:Progression Free Survival of IRX-Dura treatment participants at six months. Progression free survival is defined as the time from Day 1 of treatment to evidence of progression. Progression will be defined by RECIST v 1.1.
Measure:Median Progression-free Survival
Time Frame:Up to 12 months post treatment
Safety Issue:
Description:Median Progression Free Survival of IRX-Dura treatment participants. Progression free survival is defined as the time from Day 1 of treatment to evidence of progression. Progression will be defined by RECIST v 1.1.
Measure:Median Overall Survival (OS)
Time Frame:Up to 12 months post treatment
Safety Issue:
Description:Median Overall Survival of IRX-Dura treatment participants. OS: The length of time from the start of treatment that participants are still alive.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:H. Lee Moffitt Cancer Center and Research Institute

Last Updated