- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02614456
Combination of Interferon-gamma and Nivolumab for Advanced Solid Tumors
Combination Immunotherapy With Interferon-gamma and Nivolumab for Patients With Advanced Solid Tumors: A Phase 1 Study
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, United States, 19111
- Fox Chase Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Patients must have a histologically or cytologically confirmed metastatic solid tumor that has shown clinical or pre-clinical evidence of responding to anti-PD-1 therapy or the capacity to up-regulate PD-L1. These tumor types may include but may not be limited to: RCC, UC, melanoma, non small cell lung cancer (NSCLC), small cell lung cancer, squamous cell cancer of the head and neck (SCCHN), ovarian carcinoma, triple negative breast cancer, gastric cancer, microsatellite instability expressing (MSI-high) colon cancer, hepatocellular carcinoma, mesothelioma, gastrointestinal stromal tumors, endometrial carcinoma, liposarcomas, chondrosarcomas, and uterine sarcomas. Patients with solid tumor types not listed above may be enrolled at the discretion of the Principal Investigator.
Note: Dose expansion phase will include two cohorts and consist of patients with either metastatic UC or RCC, but must meet all other inclusion criteria.
- All patients must have received at least one line of systemic therapy in the metastatic setting. Prior immunotherapy is allowed, including prior treatment with nivolumab or another PD-1 inhibitor, as long as the reason for discontinuation of a prior PD-1 inhibitor was not for drug-related toxicity.
- Patients must have measurable disease per RECIST criteria v. 1.1 as described in detail in section 11.0.
- Patients must have a site of disease that is amenable to pretreatment and on-treatment core biopies. At least 3 formalin fixed, paraffin embedded (FFPE) slides at five microns each may be collected at each biopsy. Determination of tissue accessibility and quantity will be made by the consenting clinician. Patients must consent to the two study-required biopsy procedures.
- Age > 18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
Patients must have normal organ and marrow function as defined below:
- Absolute neutrophil count > 1,500/mcL
- Platelets > 100,000/mcL
- Total bilirubin < 1.5 times the upper limit of normal (ULN), except patients with Gilbert's syndrome in whom total bilirubin must be <3.0 mg/dL
- AST/ALT (SGOT/SGPT) < 3 times institutional normal limits
- Creatinine < 1.5 times the ULN OR Creatinine clearance > 40 mL/min (as measured or calculated by Cockroft-Gault formula)
- Ability to understand and willingness to sign a written informed consent and HIPAA consent document.
Exclusion Criteria:
- Patients who have had chemotherapy or radiotherapy within 2 weeks prior to entering the study.
- Patients may not have any active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids or immunosuppressive medications, except for syndromes which would not be expected to recur in the absence of an external trigger. Subjects with vitiligo, type I diabetes mellitus, or residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement are permitted to enroll.
- Any condition requiring systemic treatment with corticosteroids (> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days prior to first dose of study drug. Inhaled or topical steroids and adrenal replacement steroid doses > 10 mg daily prednisone or equivalent are permitted in the absence of active autoimmune disease.
- Patients may not be receiving any other investigational agents.
- Patients with known active or symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis. Asymptomatic, treated, and/or stable brain metastases, as measured by subsequent radiologic evaluations at least two months apart, are permitted.
- History of allergic reactions attributed to compound of similar chemical or biologic composition to the agent(s) used in this study.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension or psychiatric illness/social situations that would limit compliance with study requirements.
- Known human immunodeficiency virus (HIV) positive or history of acquired immune deficiency syndrome (AIDS) or AIDS-defining illness.
- Known current or a history of hepatitis B or C virus, including chronic and dormant states, unless disease has been treated and confirmed cleared.
- Any medical condition that in the investigator's opinion could interfere with interpretation of study or toxicity, or increase the risk to the patient related to potential toxicity.
- Major surgery within 4 weeks of initiation of study drug.
- Pregnant or breast feeding. Refer to section 4.4 for further detail.
- A second invasive malignancy requiring active treatment.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Interferon-gamma and nivolumab
Interferon-gamma (IFN-γ): starting dose 50 mcg/m2 subcutaneously Nivolumab: 3 mg/kg intravenously Induction phase: IFN-γ every other day alone for 1 week Combination phase: IFN-γ every other day & Nivolumab every 2 weeks for 3 months Single agent phase: Nivolumab every 3 weeks up to 1 year |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Number of participants with treatment-related adverse events as assesses by CTCAE version 4.03.
Time Frame: 58 weeks
|
58 weeks
|
Determine the recommended phase 2 dose (RP2D) based on Dose limiting toxicities
Time Frame: 6 weeks
|
6 weeks
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
To evaluate the investigator assessed ORR using standard response evaluation criteria in solid tumors (RECIST) version 1.1 for metastatic renal cell carcinoma.
Time Frame: 2 years
|
2 years
|
To evaluate the investigator assessed ORR using standard response evaluation criteria in solid tumors (RECIST) version 1.1 for metastatic urothelial cancer.
Time Frame: 2 years
|
2 years
|
To evaluate median progression free survival (PFS) using Kaplan-Meier curves for metastatic renal cell carcinoma.
Time Frame: 2 years
|
2 years
|
To evaluate median progression free survival (PFS) using Kaplan-Meier curves for metastatic urothelial cancer.
Time Frame: 2 years
|
2 years
|
To evaluate median overall survival (OS) using Kaplan-Meier curves for metastatic renal cell carcinoma.
Time Frame: 2 years
|
2 years
|
To evaluate median overall survival (OS) using Kaplan-Meier curves for metastatic urothelial cancer.
Time Frame: 2 years
|
2 years
|
To investigate the relationship between PD-L1 expression on tumor cells and on immune cells using IHC and SMI methods.
Time Frame: Baseline
|
Baseline
|
To investigate the relationship between PD-L1 expression on tumor cells and on immune cells using IHC and SMI methods.
Time Frame: week 2
|
week 2
|
To investigate the relationship between PD-L1 expression on tumor cells and on immune cells using IHC and SMI methods.
Time Frame: week 7
|
week 7
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Matthew Zibelman, MD, Fox Chase Cancer Center
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- GU-084
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Advanced Solid Tumors
-
AmgenCompletedCancer | Advanced Solid Tumors | Solid Tumors | Tumors | Advanced MalignancyUnited States, Australia
-
NantCell, Inc.CompletedQUILT-2.016: Study of AMG 479 With Biologics or Chemotherapy for Subjects With Advanced Solid TumorsCancer | Advanced Solid Tumors | Solid Tumors | Tumors | Advanced Malignancy
-
Incyte CorporationRecruitingA Study to Evaluate the Safety of INCA33890 in Participants With Advanced or Metastatic Solid TumorsAdvanced Solid Tumors | Solid Tumors | Metastatic Solid TumorsUnited States, Spain, United Kingdom, France, Italy, Denmark, Switzerland
-
Hoffmann-La RocheCompletedSolid Tumors, Advanced Solid TumorsUnited States
-
Esperance Pharmaceuticals IncCompletedAdvanced Solid Tumors | Solid TumorsUnited States
-
Incyte Biosciences Japan GKCompletedAdvanced Solid Tumors | Metastatic Solid TumorsJapan
-
Memorial Sloan Kettering Cancer CenterKyowa Hakko Kirin Pharma, Inc.CompletedAdvanced Solid Tumors | Metastatic Solid TumorsUnited States
-
Bristol-Myers SquibbCompletedAdvanced Solid Tumors | Metastatic Solid TumorsKorea, Republic of, Canada, Australia
-
Vividion Therapeutics, Inc.RecruitingAdvanced Solid Tumors | Advanced Hematologic TumorsUnited States
-
Genentech, Inc.RecruitingAdvanced Solid Tumors | Metastatic Solid TumorsCanada, Korea, Republic of, United States, Brazil, Australia, Argentina, Spain, New Zealand, Poland
Clinical Trials on interferon-gamma and nivolumab
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI); Horizon Pharma USA, Inc.TerminatedMyxoid Liposarcoma | Synovial Sarcoma | Round Cell LiposarcomaUnited States
-
SPP Pharmaclon Ltd.RecruitingPulmonary TuberculosisRussian Federation
-
SPP Pharmaclon Ltd.CompletedCommunity-acquired PneumoniaRussian Federation
-
SPP Pharmaclon Ltd.RecruitingRespiratory TuberculosisRussian Federation
-
SPP Pharmaclon Ltd.North-Western State Medical University named after I.I.MechnikovCompletedRNA Virus Infections | Lentivirus Infections | Tuberculosis, Pulmonary | Human Immunodeficiency Virus | HIV Coinfection | Aids/Hiv ProblemRussian Federation
-
NYU Langone HealthNational Heart, Lung, and Blood Institute (NHLBI)CompletedTuberculosis | AIDS-related ComplexUnited States, South Africa
-
SPP Pharmaclon Ltd.CompletedCOVID-19 Respiratory Infection | Viral PneumoniaRussian Federation
-
Nantes University HospitalActive, not recruiting
-
SPP Pharmaclon Ltd.CompletedCOVID-19 Respiratory InfectionRussian Federation
-
SPP Pharmaclon Ltd.Completed