Advanced Solid TumorsPhase 1NCT02614456
Combination of Interferon-gamma and Nivolumab for Advanced Solid Tumors
A Phase 1 study testing interferon-gamma and nivolumab in people with Advanced Solid Tumors, run by Fox Chase Cancer Center at 1 site in United States.
Trial summary
This is a phase I study of combination immunotherapy with IFN-γ and the PD-1 inhibitor nivolumab in patients with advanced solid tumors who have progressed on at least one prior systemic therapy, which may include prior immunotherapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumors
- What is being tested?
- interferon-gamma and nivolumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Dec 2015to 12 Jun 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
About this study
Official title: Combination Immunotherapy With Interferon-gamma and Nivolumab for Patients With Advanced Solid Tumors: A Phase 1 Study
This is a phase I study of combination immunotherapy with IFN-γ and the PD-1 inhibitor nivolumab in patients with advanced solid tumors who have progressed on at least one prior systemic therapy, which may include prior immunotherapy.
Read the detailed description
This is a phase I study of combination immunotherapy with IFN-γ and the PD-1 inhibitor nivolumab in patients with advanced solid tumors who have progressed on at least one prior systemic therapy, which may include prior immunotherapy. Patients will be treated with a one week induction phase (IP) of IFN-γ, followed by a combination phase (CP) with IFN-γ and nivolumab for three cycles, followed by a single agent phase of only nivolumab for up to one year. The study will primarily assess the safety and tolerability of the combination. Tumor assessments will occur after three cycles of combination therapy, then every three cycles thereafter. Secondary objectives including ORR, PFS, and OS will also be assessed, as will various correlative analyses. Initial accrual will occur using a modified 6+6 design, and if endpoints for safety (using DLT criteria) are met, expansion cohorts in RCC and UC will be opened for up to 15 patients.
- Conditions
- Advanced Solid Tumors
- Being tested
- interferon-gamma and nivolumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
interferon-gamma and nivolumabDrug
| Study group | Role | What they receive |
|---|---|---|
| Interferon-gamma and nivolumab | Experimental | 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 Receives: Drug: interferon-gamma and nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with treatment-related adverse events as assesses by CTCAE version 4.03.
Measured: 58 weeks
Determine the recommended phase 2 dose (RP2D) based on Dose limiting toxicities
Measured: 6 weeks
Secondary outcomes (9)
To evaluate the investigator assessed ORR using standard response evaluation criteria in solid tumors (RECIST) version 1.1 for metastatic renal cell carcinoma.
Measured: 2 years
To evaluate the investigator assessed ORR using standard response evaluation criteria in solid tumors (RECIST) version 1.1 for metastatic urothelial cancer.
Measured: 2 years
To evaluate median progression free survival (PFS) using Kaplan-Meier curves for metastatic renal cell carcinoma.
Measured: 2 years
To evaluate median progression free survival (PFS) using Kaplan-Meier curves for metastatic urothelial cancer.
Measured: 2 years
To evaluate median overall survival (OS) using Kaplan-Meier curves for metastatic renal cell carcinoma.
Measured: 2 years
To evaluate median overall survival (OS) using Kaplan-Meier curves for metastatic urothelial cancer.
Measured: 2 years
To investigate the relationship between PD-L1 expression on tumor cells and on immune cells using IHC and SMI methods.
Measured: Baseline
To investigate the relationship between PD-L1 expression on tumor cells and on immune cells using IHC and SMI methods.
Measured: week 2
To investigate the relationship between PD-L1 expression on tumor cells and on immune cells using IHC and SMI methods.
Measured: week 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2015 (estimated)
- Study start11 Dec 2015
- Primary completion12 Jun 2019
- Study completion12 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced Solid TumorsStudies of the same condition, open and under way.
- More trials run by Fox Chase Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fox Chase Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Horizon Pharma Ireland, Ltd., Dublin Ireland
- Responsible party
- Sponsor
- Investigators
- Matthew Zibelman, MD, Principal investigator, Fox Chase Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02614456
- Sponsor's protocol ID
- GU-084
- Status last verified
- Nov 2019
- First submitted
- 23 Nov 2015
- Last updated
- 29 Nov 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Zibelman M, MacFarlane AW 4th, Costello K, McGowan T, O'Neill J, Kokate R, Borghaei H, Denlinger CS, Dotan E, Geynisman DM, Jain A, Martin L, Obeid E, Devarajan K, Ruth K, Alpaugh RK, Dulaimi EA, Cukierman E, Einarson M, Campbell KS, Plimack ER. A phase 1 study of nivolumab in combination with interferon-gamma for patients with advanced solid tumors. Nat Commun. 2023 Jul 27;14(1):4513. doi: 10.1038/s41467-023-40028-z.
PubMed 37500647
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combination Immunotherapy With Interferon-gamma and Nivolumab for Patients With Advanced Solid Tumors: A Phase 1 Study
- ClinicalTrials.gov ID
- NCT02614456
- Acronym / sponsor ID
- GU-084
- Conditions
- Advanced Solid Tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Fox Chase Cancer CenterUniversity, hospital or other
- Collaborators
- Horizon Pharma Ireland, Ltd., Dublin Ireland
- Study start
- 11 Dec 2015 (actual)
- Primary completion
- 12 Jun 2019 (actual)
- Study completion
- 12 Jun 2019 (actual)
- First posted
- 25 Nov 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase I study of combination immunotherapy with IFN-γ and the PD-1 inhibitor nivolumab in patients with advanced solid tumors who have progressed on at least one prior systemic therapy, which may include prior immunotherapy.
Detailed description
This is a phase I study of combination immunotherapy with IFN-γ and the PD-1 inhibitor nivolumab in patients with advanced solid tumors who have progressed on at least one prior systemic therapy, which may include prior immunotherapy. Patients will be treated with a one week induction phase (IP) of IFN-γ, followed by a combination phase (CP) with IFN-γ and nivolumab for three cycles, followed by a single agent phase of only nivolumab for up to one year. The study will primarily assess the safety and tolerability of the combination. Tumor assessments will occur after three cycles of combination therapy, then every three cycles thereafter. Secondary objectives including ORR, PFS, and OS will also be assessed, as will various correlative analyses. Initial accrual will occur using a modified 6+6 design, and if endpoints for safety (using DLT criteria) are met, expansion cohorts in RCC and UC will be opened for up to 15 patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Interferon-gamma and nivolumab | Experimental | Drug: interferon-gamma and nivolumabInterferon-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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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.
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| interferon-gamma and nivolumab | Drug | Interferon-gamma and nivolumab |
Primary outcome
Number of participants with treatment-related adverse events as assesses by CTCAE version 4.03.
Time frame: 58 weeks
Determine the recommended phase 2 dose (RP2D) based on Dose limiting toxicities
Time frame: 6 weeks
9 secondary outcomes
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
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
To evaluate median progression free survival (PFS) using Kaplan-Meier curves for metastatic renal cell carcinoma.
Time frame: 2 years
To evaluate median progression free survival (PFS) using Kaplan-Meier curves for metastatic urothelial cancer.
Time frame: 2 years
To evaluate median overall survival (OS) using Kaplan-Meier curves for metastatic renal cell carcinoma.
Time frame: 2 years
To evaluate median overall survival (OS) using Kaplan-Meier curves for metastatic urothelial cancer.
Time frame: 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
To investigate the relationship between PD-L1 expression on tumor cells and on immune cells using IHC and SMI methods.
Time frame: 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Nov 2019.
- Derived from this study: PubMed 37500647Zibelman M, MacFarlane AW 4th, Costello K, McGowan T, O'Neill J, Kokate R, Borghaei H, Denlinger CS, Dotan E, Geynisman DM, Jain A, Martin L, Obeid E, Devarajan K, Ruth K, Alpaugh RK, Dulaimi EA, Cukierman E, Einarson M, Campbell KS, Plimack ER. A phase 1 study of nivolumab in combination with interferon-gamma for patients with advanced solid tumors. Nat Commun. 2023 Jul 27;14(1):4513. doi: 10.1038/s41467-023-40028-z.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matthew Zibelman, MD principal investigator
Fox Chase Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing interferon-gamma and nivolumab in people with Advanced Solid Tumors, run by Fox Chase Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with treatment-related adverse events as assesses by CTCAE version 4.03. (time frame: 58 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02614456, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Nov 2019.