Working… Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02636036
Recruitment Status : Recruiting
First Posted : December 21, 2015
Last Update Posted : March 4, 2019
Bristol-Myers Squibb
Syneos Health
Information provided by (Responsible Party):
PsiOxus Therapeutics Ltd

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Bladder Carcinoma Squamous Cell Carcinoma of the Head and Neck Salivary Gland Cancer Non Small Cell Lung Cancer Biological: enadenotucirev Biological: nivolumab Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 135 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Multicenter, Open Label Study of Enadenotucirev Combined With PD-1 Inhibitor in Subjects With Metastatic or Advanced Epithelial Tumors
Actual Study Start Date : January 2016
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2021

Arm Intervention/treatment
Experimental: enadenotucirev and nivolumab Biological: enadenotucirev
Biological: nivolumab

Primary Outcome Measures :
  1. Incidence, nature and severity of adverse events (safety and tolerability) in study of enadenotucirev administered in combination with a PD-1 inhibitor [ Time Frame: 12 months ]
    Review of adverse events including serious adverse events (SAEs), adverse events meeting protocol defined DLT criteria, adverse events leading to study treatment or study discontinuation, and adverse events resulting in death

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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Adult males or females aged 18 years or over
  • Disease status:

    • Dose escalation phase only: Diagnosis of metastatic or advanced CRC, UCC, SCCHN, salivary gland cancer or NSCLC with tumor accessible for biopsy not responding to standard therapy or for whom no standard treatment exists
    • Dose expansion only: Subjects with pathologically confirmed locally advanced or metastatic disease of the following tumor types:
    • CRC - MSS or microsatellite MSI-L
    • SCCHN - Must have received only one line of PDL-1/PD-1 as most recent therapy and Prior radiotherapy must have been completed at least 8 weeks prior to enrolment if radiotherapy was to the head and neck region for curative intent and 2 weeks prior to enrolment if radiotherapy was to other regions
    • NSCLC - Must have received only one line of prior PDL-1/PD-1 as most recent therapy and no more than two prior lines (for EGFR/ALK wild type) and no more than three prior lines (for EGFR/ALK mutant, including two tyrosine kinase inhibitors)
  • 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
  • Prior palliative radiotherapy completed at least 3 weeks before study treatment administration
  • 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
  • Non-impaired renal function:

    • Creatinine ≤1.5 mg/dL and estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73m2 or measured creatinine clearance ≥60 mL/min
    • Proteinuria: urine dipstick at screening and baseline negative or trace. Subjects may be included with results of 1+ if they have a spot urinary albumin creatinine ratio (ACR) of either (i) ≤3 mg/mmol or (ii) >3 mg-<70 mg/mmol with a 24 hour urinary protein <0.2 g/24 hours
  • 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 ≥1.5X10^9/L
    • Platelets ≥100 x 10^9/L
    • Hemoglobin ≥90 g/L
  • Adequate coagulation tests: international normalized ratio ≤1.5
  • For females of childbearing potential (defined as <2 years after last menstruation or not surgically sterile), a negative serum pregnancy test must be documented within 72 hours of 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 5 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 7 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
  • Serum complement (C3/C4 proteins) above the lower limit of normal range

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
  • Any history of renal disease, renal injury or auto-immune disease. 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 providing they comply with the other eligibility criteria relating to renal function
  • 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 2 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

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 identifier (NCT number): NCT02636036

Layout table for location contacts
Contact: PsiOxus Therapeutics

Layout table for location information
United States, Arizona
University of Arizona Cancer Center, 1515 North Campbell Ave. Recruiting
Tucson, Arizona, United States, 85724
Contact: Daruka Mahadevan, MD   
Contact: Ruth Cañamar, BA   
United States, California
City of Hope Comprehensive Cancer Center, 1500 E Duarte Str. Recruiting
Duarte, California, United States, 91010
Contact: Marwan Fakih, MD   
Contact: Mengsha Li, MS, CCRP   
UCLA Medical Center, 10945 Le Conte Ave, Ste. 3360 Recruiting
Santa Monica, California, United States, 90095
Contact: Lee Rosen, MD   
Contact: Suzanne Nichols, RN   
United States, Indiana
Horizon Oncology Research, 1345 Unity Place, Suite 345 Recruiting
Lafayette, Indiana, United States, 47905
Contact: Wael Harb, MD   
United States, Michigan
Henry Ford Hospital, 2799 West Grand Blvd. Recruiting
Detroit, Michigan, United States, 48202
Contact: Ding Wang, MD   
Contact: Karie Gignac, RN   
United States, Tennessee
Vanderbilt-Ingram Cancer Center Recruiting
Nashville, Tennessee, United States, 37232-6307
Contact: Jordan Berlin, MD   
Contact: Tom Leonard-Martin, PhD, MPH   
Sponsors and Collaborators
PsiOxus Therapeutics Ltd
Bristol-Myers Squibb
Syneos Health

Layout table for additonal information
Responsible Party: PsiOxus Therapeutics Ltd Identifier: NCT02636036     History of Changes
Other Study ID Numbers: ColoAd1-1003
First Posted: December 21, 2015    Key Record Dates
Last Update Posted: March 4, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Squamous Cell Carcinoma of Head and Neck
Salivary Gland Neoplasms
Urinary Bladder Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms by Site
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Mouth Neoplasms
Mouth Diseases
Stomatognathic Diseases
Salivary Gland Diseases
Urologic Neoplasms
Urogenital Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Antineoplastic Agents, Immunological
Antineoplastic Agents