Phase I Study of Enadenotucirev and PD-1 Inhibitor in Subjects With Metastatic or Advanced Epithelial Tumors (SPICE)
Primary Purpose
Colorectal Cancer, Squamous Cell Carcinoma of the Head and Neck, Epithelial Tumor
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
enadenotucirev
nivolumab
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Cancer focused on measuring metastatic; epithelial; advanced
Eligibility Criteria
Inclusion Criteria:
- Adult males or females aged 18 years or over
- Disease status: - Diagnosis of metastatic or advanced CRC, UCC, SCCHN, salivary gland cancer or NSCLC not responding to standard therapy or for whom no standard treatment exists
- For patients who have received prior PD-1 / PD-L1 therapy (Cohorts 7A and 7B and dose expansion phase only): Prior PD-1 / PD-L1 inhibitor therapy in current line of treatment for ≥6 weeks and ≤4 months, with best response of stable disease or progressive disease
- 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 lung function
- Adequate renal function
- Adequate hepatic function
- Adequate bone marrow function
- Adequate coagulation tests: PT and aPTT within normal range or international normalized ratio (INR) ≤1.5
- Meeting reproductive status requirements
- Subjects must provide written informed consent to participate
- Willing to consent to tumour biopsies during the study
Exclusion Criteria:
- Pregnant or breastfeeding females
- Known history or evidence of significant immunodeficiency due to underlying illness
- Splenectomy
- Prior allogeneic or autologous bone marrow or organ transplantation
- Any history of renal disease, renal injury or auto-immune disease.
- History of idiopathic pulmonary fibrosis, drug induced pneumonitis, evidence of active pneumonia or pneumonitis on computed tomography scan
- Clinically or radiologically suspected, or evidence of, lymphangitic carcinomatosis
- 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 4 weeks before the first dose of study treatment
- For Cohort 1 to 6:Prior treatment with PD-1 and programmed death ligand (PD-L)1 inhibitors
- For Cohorts 7A and 7B and dose expansion phase: History of Grade >2 or currently uncontrolled immune-related AEs while being treated with PD-1 / PD-L1 inhibitors
- For Cohorts 7A and 7B and dose expansion phase: Patients with progressive disease with ≥50% increase in disease burden from start of PD-1 / PD-L1 inhibitor therapy in the most recent line of treatment are excluded
- Major surgery or treatment with any chemotherapy (bisphosphonate therapy or treatment with receptor activator of nuclear factor kappa-Β l(RANK)-ligand inhibitors for metastatic bone disease is permitted), biologics for cancer or investigational therapy in the 28 days before the first dose of study treatment (patients 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 and decision is supported by the half-life of previous therapy). All toxicities attributed to prior anti-cancer therapy other than alopecia must have resolved to Grade 1 or baseline before the first dose of study treatment. Patients 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 enroll Note: This does not apply to anti-PD-1 / PD-L1 if in the patient's current line of therapy, and anti-PD-1 / PD-L1 treatment may continue during screening
- 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. Patients 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 14 days before the first dose of study treatment. Both surgery and or radiotherapy must have been completed at least 2 weeks before 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 patient 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
- History of myocardial infarction or significant cardiovascular or cerebrovascular event in the 12 months before the first dose of study treatment
- An increased risk due to tumour flare, as assessed by the Investigator (e.g. an initial increase in tumour size that may lead to intestinal obstruction, obstruction of the ureter or airway)
- Penetrating tumour infiltration of major blood vessels, pericardium, gastrointestinal tract or other hollow organs that may lead to perforation due to tumour necrosis
- History of DVT or pulmonary embolus in the 12 months before the first dose of study treatment
- History of significant bleeding requiring hospitalization in the 12 months before the first dose of study treatment
- Patients receiving therapeutic or prophylactic anticoagulation therapy
Sites / Locations
- University of Arizona Cancer Center, 1515 North Campbell Ave.
- City of Hope Comprehensive Cancer Center, 1500 E Duarte Str.
- UCLA Medical Center, 10945 Le Conte Ave, Ste. 3360
- Horizon Oncology Research, 1345 Unity Place, Suite 365
- Henry Ford Hospital, 2799 West Grand Blvd.
- Vanderbilt-Ingram Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
enadenotucirev and nivolumab
Arm Description
Outcomes
Primary Outcome Measures
Incidence, nature and severity of adverse events (safety and tolerability) in study of enadenotucirev administered in combination with a PD-1 inhibitor
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
Maximum Tolerated and/or Maximum Feasible Dose
Maximum tolerated dose (MTD) / maximum feasible dose (MFD) of enadenotucirev administered IV in combination with nivolumab.
Secondary Outcome Measures
Full Information
NCT ID
NCT02636036
First Posted
November 20, 2015
Last Updated
November 2, 2021
Sponsor
Akamis Bio
Collaborators
Bristol-Myers Squibb, Syneos Health
1. Study Identification
Unique Protocol Identification Number
NCT02636036
Brief Title
Phase I Study of Enadenotucirev and PD-1 Inhibitor in Subjects With Metastatic or Advanced Epithelial Tumors
Acronym
SPICE
Official Title
A Phase I Multicenter, Open Label Study of Enadenotucirev Combined With PD-1 Inhibitor in Subjects With Metastatic or Advanced Epithelial Tumors
Study Type
Interventional
2. Study Status
Record Verification Date
November 2021
Overall Recruitment Status
Completed
Study Start Date
January 25, 2016 (Actual)
Primary Completion Date
October 8, 2021 (Actual)
Study Completion Date
October 8, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Akamis Bio
Collaborators
Bristol-Myers Squibb, Syneos Health
4. Oversight
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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, escalation phase), not responding to standard therapy.
Detailed Description
To characterise the safety and tolerability of enadenotucirev administered in combination with nivolumab in subjects with metastatic or advanced epithelial tumours.
A dose escalation phase is conducted in subjects with solid tumors of epithelial origin not responding to standard therapy to establish the MTD/MFD and optimum dosing schedule of the enadenotucirev and nivolumab combination treatment.
A dose expansion phase will further outline the dose level and schedule of enadenotucirev and nivolumab combination treatment and investigate signals of efficacy in three cohorts of subjects with specific epithelial tumour types.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer, Squamous Cell Carcinoma of the Head and Neck, Epithelial Tumor
Keywords
metastatic; epithelial; advanced
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
51 (Actual)
8. Arms, Groups, and Interventions
Arm Title
enadenotucirev and nivolumab
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
enadenotucirev
Intervention Type
Biological
Intervention Name(s)
nivolumab
Primary Outcome Measure Information:
Title
Incidence, nature and severity of adverse events (safety and tolerability) in study of enadenotucirev administered in combination with a PD-1 inhibitor
Description
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
Time Frame
12 months
Title
Maximum Tolerated and/or Maximum Feasible Dose
Description
Maximum tolerated dose (MTD) / maximum feasible dose (MFD) of enadenotucirev administered IV in combination with nivolumab.
Time Frame
12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adult males or females aged 18 years or over
Disease status: - Diagnosis of metastatic or advanced CRC, UCC, SCCHN, salivary gland cancer or NSCLC not responding to standard therapy or for whom no standard treatment exists
For patients who have received prior PD-1 / PD-L1 therapy (Cohorts 7A and 7B and dose expansion phase only): Prior PD-1 / PD-L1 inhibitor therapy in current line of treatment for ≥6 weeks and ≤4 months, with best response of stable disease or progressive disease
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 lung function
Adequate renal function
Adequate hepatic function
Adequate bone marrow function
Adequate coagulation tests: PT and aPTT within normal range or international normalized ratio (INR) ≤1.5
Meeting reproductive status requirements
Subjects must provide written informed consent to participate
Willing to consent to tumour biopsies during the study
Exclusion Criteria:
Pregnant or breastfeeding females
Known history or evidence of significant immunodeficiency due to underlying illness
Splenectomy
Prior allogeneic or autologous bone marrow or organ transplantation
Any history of renal disease, renal injury or auto-immune disease.
History of idiopathic pulmonary fibrosis, drug induced pneumonitis, evidence of active pneumonia or pneumonitis on computed tomography scan
Clinically or radiologically suspected, or evidence of, lymphangitic carcinomatosis
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 4 weeks before the first dose of study treatment
For Cohort 1 to 6:Prior treatment with PD-1 and programmed death ligand (PD-L)1 inhibitors
For Cohorts 7A and 7B and dose expansion phase: History of Grade >2 or currently uncontrolled immune-related AEs while being treated with PD-1 / PD-L1 inhibitors
For Cohorts 7A and 7B and dose expansion phase: Patients with progressive disease with ≥50% increase in disease burden from start of PD-1 / PD-L1 inhibitor therapy in the most recent line of treatment are excluded
Major surgery or treatment with any chemotherapy (bisphosphonate therapy or treatment with receptor activator of nuclear factor kappa-Β l(RANK)-ligand inhibitors for metastatic bone disease is permitted), biologics for cancer or investigational therapy in the 28 days before the first dose of study treatment (patients 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 and decision is supported by the half-life of previous therapy). All toxicities attributed to prior anti-cancer therapy other than alopecia must have resolved to Grade 1 or baseline before the first dose of study treatment. Patients 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 enroll Note: This does not apply to anti-PD-1 / PD-L1 if in the patient's current line of therapy, and anti-PD-1 / PD-L1 treatment may continue during screening
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. Patients 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 14 days before the first dose of study treatment. Both surgery and or radiotherapy must have been completed at least 2 weeks before 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 patient 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
History of myocardial infarction or significant cardiovascular or cerebrovascular event in the 12 months before the first dose of study treatment
An increased risk due to tumour flare, as assessed by the Investigator (e.g. an initial increase in tumour size that may lead to intestinal obstruction, obstruction of the ureter or airway)
Penetrating tumour infiltration of major blood vessels, pericardium, gastrointestinal tract or other hollow organs that may lead to perforation due to tumour necrosis
History of DVT or pulmonary embolus in the 12 months before the first dose of study treatment
History of significant bleeding requiring hospitalization in the 12 months before the first dose of study treatment
Patients receiving therapeutic or prophylactic anticoagulation therapy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tom Lillie, MD
Organizational Affiliation
Psioxus Theraputics
Official's Role
Study Director
Facility Information:
Facility Name
University of Arizona Cancer Center, 1515 North Campbell Ave.
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
Facility Name
City of Hope Comprehensive Cancer Center, 1500 E Duarte Str.
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
UCLA Medical Center, 10945 Le Conte Ave, Ste. 3360
City
Santa Monica
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Horizon Oncology Research, 1345 Unity Place, Suite 365
City
Lafayette
State/Province
Indiana
ZIP/Postal Code
47905
Country
United States
Facility Name
Henry Ford Hospital, 2799 West Grand Blvd.
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Vanderbilt-Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232-6307
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Phase I Study of Enadenotucirev and PD-1 Inhibitor in Subjects With Metastatic or Advanced Epithelial Tumors
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