Clinical Trials /

Phase I Study of Enadenotucirev and PD-1 Inhibitor in Subjects With Metastatic or Advanced Epithelial Tumors

NCT02636036

Description:

This is a Phase I multicenter, open label, nonrandomized study of enadenotucirev administered in combination with nivolumab in subjects with metastatic or advanced epithelial tumors (with focus on CRC, SCCHN, UCC, (escalation phase), NSCLC and salivary gland cancer) not responding to standard therapy.

Related Conditions:
  • Colorectal Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Salivary Gland Carcinoma
  • Transitional Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Phase I Study of Enadenotucirev and PD-1 Inhibitor in Subjects With Metastatic or Advanced Epithelial Tumors
  • Official Title: A Phase I Multicenter, Open Label Study of Enadenotucirev Combined With PD-1 Inhibitor in Subjects With Metastatic or Advanced Epithelial Tumors

Clinical Trial IDs

  • ORG STUDY ID: ColoAd1-1003
  • NCT ID: NCT02636036

Conditions

  • Colorectal Cancer
  • Bladder Carcinoma
  • Squamous Cell Carcinoma of the Head and Neck
  • Salivary Gland Cancer

Interventions

DrugSynonymsArms
enadenotucirevenadenotucirev and nivolumab
nivolumabenadenotucirev and nivolumab

Purpose

This is a Phase I multicenter, open label, nonrandomized study of enadenotucirev administered in combination with nivolumab in subjects with metastatic or advanced epithelial tumors (with focus on CRC, UCC, SCCHN and salivary gland cancer) not responding to standard therapy.

Trial Arms

NameTypeDescriptionInterventions
enadenotucirev and nivolumabExperimental

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Adult males or females aged 18 years or over
    
              -  Diagnosis of metastatic or advanced CRC, UCC, SCCHN, salivary gland cancer or NSCLC
                 with tumor accessible for biopsy
    
              -  Dose expansion only: Subjects must have at least one measurable site of disease
                 according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria; this
                 lesion must be outside a previously irradiated area
    
              -  Disease status:
    
                   -  Dose escalation phase only: Subject not responding to standard therapy or for
                      whom no standard treatment exists
    
                   -  Dose expansion phase: Subject not responding to standard therapy or for whom no
                      standard treatment exists with:
    
                   -  CRC - No more than four different prior lines of systemic therapy for advanced
                      disease
    
                   -  UCC and SCCHN and salivary gland cancer - No more than three different prior
                      treatment regimens in the advanced/metastatic setting with a maximum of two
                      chemotherapy-containing regimens
    
                   -  NSCLC - Prior treatment regimens must include a platinum-based therapy
    
              -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
    
              -  Predicted life expectancy of 3 months or more
    
              -  Ability to comply with study procedures in the Investigator's opinion
    
              -  Recovered to Grade 1 from the effects (excluding alopecia) of any prior therapy for
                 their malignancies
    
              -  Adequate renal function:
    
                   -  Creatinine ≤1.5 mg/dL or calculated creatinine clearance using the
                      Cockcroft-Gault formula ≥60 mL/min or measured creatinine clearance
    
                   -  Proteinuria: dipstick ≤2+
    
              -  Adequate hepatic function:
    
                   -  Serum bilirubin <1.5 mg/dL (except subjects with Gilbert's syndrome who may have
                      total bilirubin <3.0 mg/mL)
    
                   -  Aspartate aminotransferase and alanine aminotransferase ≤3 x upper limit of
                      normal (ULN)
    
                   -  Albumin ≥3 g/dL
    
                   -  Lipase: 1.5 x ULN. Subjects with lipase >1.5 x ULN may enrol if there are neither
                      clinical or radiographic signs of pancreatitis
    
                   -  Amylase: 1.5 x ULN. Subjects with amylase >1.5 x ULN may enrol if there are
                      neither clinical or radiographic signs of pancreatitis
    
              -  Adequate bone marrow function:
    
                   -  Absolute neutrophil count ≥1.5 x 109/L
    
                   -  Platelets ≥100 x 109/L
    
                   -  Hemoglobin ≥90 g/L
    
              -  Adequate coagulation tests: international normalized ratio ≤1.5
    
              -  Normal thyroid and pituitary functions
    
              -  For females of childbearing potential (defined as <2 years after last menstruation or
                 not surgically sterile), a negative serum pregnancy test must be documented in the 14
                 days before the first dose of study treatment For females who are not postmenopausal
                 (24 months of amenorrhea) or surgically sterile (absence of ovaries and/or uterus):
                 agreement to use two adequate methods of contraception, during the study treatment
                 period and for at least 6 months after the last dose of study treatment For males:
                 agreement to use a barrier method of contraception during the study treatment period
                 and for at least 6 months after the last dose of study treatment
    
              -  Subjects must provide written informed consent to participate
    
              -  Willing to consent to tumor biopsies during the study
    
            Exclusion Criteria:
    
              -  Pregnant or breastfeeding females
    
              -  Known history or evidence of significant immunodeficiency due to underlying illness
                 (e.g. human immunodeficiency virus [HIV]/acquired immunodeficiency syndrome [AIDS])
                 and/or medication (e.g. systemic corticosteroids or other immunosuppressive
                 medications, including cyclosporine, azathioprine, interferons in the 4 weeks before
                 the first dose of study treatment). Subjects with a condition requiring systemic
                 treatment with either corticosteroids (>10 mg daily prednisolone equivalent) or other
                 immunosuppressive medications within 14 days of the first dose of study treatment.
                 Inhaled or topical steroids and adrenal replacement steroid doses are permitted in the
                 absence of autoimmune disease
    
              -  Splenectomy
    
              -  Prior allogeneic or autologous bone marrow or organ transplantation
    
              -  Subjects with active, known or suspected auto-immune disease or a syndrome that
                 requires systemic or immunosuppressive agents; subjects with vitiligo, type I diabetes
                 mellitus, residual hypothyroidism due to autoimmune disease only requiring hormone
                 replacement, psoriasis not requiring systemic treatment or conditions not expected to
                 recur in the absence of an external trigger are permitted to enrol
    
              -  History of idiopathic pulmonary fibrosis, drug induced pneumonitis, evidence of active
                 pneumonia or pneumonitis on computed tomography scan
    
              -  Active infections requiring antibiotics, physician monitoring or recurrent fevers
                 >100.4˚F (38.0˚C) associated with a clinical diagnosis of active infection
    
              -  Active viral disease or positive test for hepatitis B virus using hepatitis B surface
                 antigen test or positive test for hepatitis C virus (HCV) using HCV ribonucleic acid
                 or HCV antibody test indicating acute or chronic infection. Positive test for HIV or
                 AIDS; testing is not required in the absence of history
    
              -  Use of the following antiviral agents: ribavirin, adefovir, lamivudine or cidofovir
                 within 7 days prior to the first dose of study treatment; or pegylated interferon in
                 the 14 days before the first dose of study treatment
    
              -  Prior treatment with PD-1 and programmed death ligand (PD-L)1 inhibitors
    
              -  Administration of an investigational drug in the 28 days before the first dose of
                 study treatment
    
              -  Major surgery or treatment with any chemotherapy, radiation therapy, biologics for
                 cancer or investigational therapy in the 28 days before the first dose of study
                 treatment (subjects with prior cytotoxic or investigational products <3 weeks prior to
                 study treatment might be eligible after discussion between the Investigator and
                 Medical Monitor, if toxicities from the prior treatment have been resolved to NCI
                 CTCAE Grade 1). All toxicities attributed to prior anti-cancer therapy other than
                 alopecia and fatigue must have resolved to Grade 1 or baseline before the first dose
                 of study treatment. Subjects with toxicities attributed to prior anti-cancer therapy
                 which are not expected to resolve and result in long lasting sequelae, such as
                 neuropathy after platinum based therapy, are permitted to enrol
    
              -  Other prior malignancy active within the previous 3 years except for local or organ
                 confined early stage cancer that has been definitively treated with curative intent,
                 does not require ongoing treatment, has no evidence of residual disease and has a
                 negligible risk of recurrence and is therefore unlikely to interfere with the primary
                 and secondary endpoints of the study, including response rate and safety
    
              -  Symptomatic brain metastases or any leptomeningeal metastasis that is symptomatic
                 and/or requires treatment. Subjects with brain metastases are eligible if these have
                 been locally treated (surgery, radiotherapy). There must also be no requirement for
                 immunosuppressive doses of systemic corticosteroids (>10 mg/day prednisone equivalent)
                 for at least 2 weeks before the first dose of study treatment
    
              -  Any serious or uncontrolled medical disorder that, in the opinion of the Investigator
                 or the Medical Monitor, may increase the risk associated with study participation or
                 study treatment administration, impair the ability of the subject to receive protocol
                 therapy or interfere with the interpretation of study results
    
              -  Known allergy to enadenotucirev, nivolumab or their excipients
    
              -  Any other medical or psychological condition that would preclude participation in the
                 study or compromise ability to give informed consent
    
              -  Dependence on continuous supplemental oxygen use
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Maximum Tolerated and/or Maximum Feasible Dose
    Time Frame:12 months
    Safety Issue:
    Description:Maximum tolerated dose (MTD) / maximum feasible dose (MFD) of enadenotucirev administered IV in combination with nivolumab.

    Secondary Outcome Measures

    Measure:to assess the blood levels of enadenotucirev following combination treatment
    Time Frame:12 months
    Safety Issue:
    Description:Enadenotucirev blood level samples will be taken on each enadenotucirev dosing day, pre-dose on pembrolizumab dosing day and at the end of study treatment visit. Measurements of enadenotucirev will be in vp/ml
    Measure:To examine the anti-tumor activity of combination treatment with enadenotucirev and nivolumab
    Time Frame:12 months
    Safety Issue:
    Description:Overall response rate according to RECIST Version 1.1
    Measure:To examine the anti-tumor activity of combination treatment with enadenotucirev and nivolumab
    Time Frame:12 months
    Safety Issue:
    Description:Overall response rate according to irRECIST Version 1.1

    Details

    Phase:Phase 1
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:PsiOxus Therapeutics Ltd

    Last Updated

    February 15, 2017