Metastatic Malignant Solid NeoplasmPhase 1NCT03525925
Ibrutinib and Nivolumab in Treating Participants With Metastatic Solid Tumors
A Phase 1 study testing Ibrutinib, Laboratory Biomarker Analysis and Nivolumab in people with Metastatic Malignant Solid Neoplasm, run by Ohio State University Comprehensive Cancer Center at 1 site in United States.
Trial summary
This phase I trial studies how well ibrutinib and nivolumab work in treating participants with solid tumors that have spread to other places in the body. Ibrutinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Metastatic Malignant Solid Neoplasm
- What is being tested?
- Ibrutinib, Laboratory Biomarker Analysis and Nivolumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Jul 2018to 31 Jul 2022
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients with biopsy-proven metastatic solid tumor and be eligible to receive nivolumab per standard of care
- Patients will be allowed to have any number of prior lines of therapy for metastatic cancer
- Patients with measurable and non-measurable disease are allowed to participate
- Absolute neutrophil count (ANC) ? 1.5 x 10^3/mm^3
- Hemoglobin (Hgb) ? 9 g/dL
- Platelet count ? 100 x10^3/mm^3
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- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ? 2.5 x upper limit of normal (ULN) or ? 5 x ULN in patients with liver metastases
- Prothrombin time ? 1.5 x ULN
- Total bilirubin ? 1.5 x ULN (unconjugated bilirubin of < 3 x ULN for patients with known Gilbert syndrome)
- Creatinine clearance of ? 50 ml/min by Cockcroft-Gault equation
- Corrected QT interval of < 480 msec (using either Bazett?s or Fridericia's formula)
- Life expectancy of > 12 weeks
- Eastern Cooperative Oncology Group (ECOG) performance status 0 ? 2
- Sexually active women with child bearing potential must have a negative pregnancy test obtained within 14 days prior to initiating study treatment
- Sexually active women of child-bearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation and for 3 months after completion of study treatment administration; adequate contraception includes methods such as oral contraceptives, double barrier method (condom plus spermicide or diaphragm), or abstaining from sexual intercourse
Who cannot join
- History of prior therapy with ibrutinib or nivolumab
- Unable to swallow capsules or having disease that is significantly affecting gastrointestinal function and/or inhibiting small intestine absorption
- Diagnosis of congenital or acquired immunodeficiency with the exception of chemotherapy induced immune suppression
- Active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids of greater than or equal to prednisone 10 mg/day or other immunosuppressive agents; patients with history of adequately treated Hashimoto?s thyroiditis will be eligible; patients requiring a short course of a high dose prednisone burst to treat asthma or common obstructive pulmonary disease will also be eligible 5 days following completion of the prednisone treatment
- Use of systemic steroids at a dose above 10 mg/day of prednisone or prednisone equivalent in cycle 1 of study therapy; systemic steroids must be discontinued at least 5 days prior to initiating study therapy; exception will be given to patients who develop immune related adverse events that necessitate use of steroids or other immune suppressive agents; following cycle 1 of study treatment, the use of systemic steroids will be allowed per discretion of the treating physician
- Active, non-infectious pneumonitis
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- Ongoing or active infection requiring systemic therapy
- History of being positive for human immunodeficiency virus (HIV)
- History of hepatitis B or C
- History of receiving live vaccine within 30 days of planned start of study therapy
- Central nervous system (CNS) metastases or leptomeningeal carcinomatosis; patients with history of adequately treated brain metastases that are stable for > 2 weeks prior to the first dose of study regimen are eligible as long they no longer require steroids and have no seizures or worsening focal neurologic symptoms; anti-epileptic therapy will be allowed
- Patients who had prior systemic chemotherapy within 3 weeks (or < 5 half-lives ? whichever is longer)
- Prior radiation therapy within 2 weeks of study enrollment
- Prior investigational therapy within 4 weeks
- Major surgery within 4 weeks or minor surgery within 2 weeks prior to the first dose of study drug; port placement will not be considered major or minor surgery
- Any inter-current, uncontrolled systemic illness or any medical or psychiatric condition that in the opinion of the investigator would make the study therapy unsafe to the patient
- Unable to understand and sign informed consent form
- Uncontrolled, active cardiovascular disease including, but not limited to: symptomatic congestive heart failure, any class 3 or 4 cardiac disease as defined by the New York Heart Association functional classification, unstable angina pectoris, cardiac arrhythmia
- Any medications or substances that are strong inhibitors or inducers of CYP 3A4 need to be discontinued prior to initiation the study therapy and for the duration of ibrutinib treatment; patients can resume these medications 3 days after completion of ibrutinib course
- History of allergic reactions attributed to compounds of similar chemical or biologic composition as ibrutinib or nivolumab
Trial locations and contacts
1 site in 1 country.
United States1 site
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
About this study
Official title: Pilot Study Testing the Effects of BTK Inhibitor Ibrutinib on Levels and Function of Myeloid Derived Suppressor Cells and Other Immune Subsets in Patients With Metastatic Solid Tumors
This phase I trial studies how well ibrutinib and nivolumab work in treating participants with solid tumors that have spread to other places in the body. Ibrutinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as nivolumab, may interfere with the ability of tumor cells to grow and spread. Giving ibrutinib and nivolumab may work better in treating participants with solid tumors.
Read the detailed description
PRIMARY OBJECTIVES:
- Evaluate the effect of the ibrutinib therapy on circulating levels of myeloid derived suppressor cells MDSC.
SECONDARY OBJECTIVES:
- Assess safety of the study combination in study subjects.
EXPLORATORY OBJECTIVES:
- Evaluate the effect of the ibrutinib/nivolumab therapy on circulating levels of MDSC.
II. Evaluate the effect of the ibrutinib and ibrutinib/nivolumab therapy on the immunosuppressive function of circulating MDSC by measuring their ability to inhibit T cell proliferation and natural killer cell mediated antibody dependent cell cytotoxicity.
III. Study the effect of ibrutinib and ibrutinib/nivolumab therapy on levels of circulating innate and adaptive immune cells such as natural killer cell and T lymphocyte subsets.
IV. Study circulating MDSC levels at the time of disease progression. V. Evaluate in a preliminary fashion the effect of the regimen on progression-free survival.
OUTLINE:
Participants receive ibrutinib orally (PO) daily for 15 days. After 7 days receiving ibrutinib, participants receive nivolumab intravenously (IV) over 60 minutes on days 1 and 15. Courses with nivolumab repeat every 28 days in the absence of disease progression or unaccepted toxicity.
After completion of study treatment, participants are followed up every 3 months.
- Conditions
- Metastatic Malignant Solid Neoplasm
- Medical subject headings
- Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IbrutinibDrug
Also called BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765
Given PO
Laboratory Biomarker AnalysisOther
Correlative studies
NivolumabBiological
Also called BMS-936558, MDX-1106, NIVO, ONO-4538
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (ibrutinib, nivolumab) | Experimental | Participants receive ibrutinib PO daily for 15 days. After 7 days receiving ibrutinib, participants receive nivolumab IV over 60 minutes on days 1 and 15. Courses with nivolumab repeat every 28 days in the absence of disease progression or unaccepted toxicity. Receives: Drug: Ibrutinib; Other: Laboratory Biomarker Analysis; Biological: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Circulating levels of myeloid derived suppressor cells
Will be summarized using descriptive statistics (N, mean, standard deviation, median, minimum, and maximum) and/or frequency and percentages for medically relevant categories. Changes of the continuous variables will be estimated using mixed model for repeated measures with proper data transformation as needed, and two-way tables and Chi-Square test will be used to summarize the changes of the categorical data.
Measured: Up to 2 years
Secondary outcomes (2)
Incidence of adverse events
Will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Will be presented using frequencies and percentages.
Measured: Up to 2 years
Progression free survival
One year progression free survival will be defined as proportion of patients who are free of disease progression or death (whichever occurs first) after 1 year of follow up. Progression free survival will be summarized using Kaplan and Meier methods, where patients who are event-free at the time of their last evaluation will be censored at that time point.
Measured: Interval from study enrollment to first documented disease progression according to Response Evaluation Criteria in Solid Tumors 1.1 or death from any cause (whichever occurs first), assessed at 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2018
- Study start18 Jul 2018
- Primary completion20 Feb 2020
- Study completion31 Jul 2022
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 Metastatic Malignant Solid NeoplasmStudies of the same condition, open and under way.
- More trials run by Ohio State University Comprehensive 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
- 16 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Robert Wesolowski, Ohio State University Comprehensive Cancer Center
- Investigators
- Robert Wesolowski, MD, Principal investigator, Ohio State University Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03525925
- Sponsor's protocol ID
- OSU-18015
- Other IDs
- NCI-2018-00423
- Status last verified
- Mar 2024
- First submitted
- 3 May 2018
- Last updated
- 18 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Schwarz E, Benner B, Wesolowski R, Quiroga D, Good L, Sun SH, Savardekar H, Li J, Jung KJ, Duggan MC, Lapurga G, Shaffer J, Scarberry L, Konda B, Verschraegen C, Kendra K, Shah M, Rupert R, Monk P, Shah HA, Noonan AM, Bixel K, Hays J, Wei L, Pan X, Behbehani G, Hu Y, Elemento O, Chung D, Xin G, Blaser BW, Carson WE 3rd. Inhibition of Bruton's tyrosine kinase with PD-1 blockade modulates T cell activation in solid tumors. JCI Insight. 2024 Nov 8;9(21):e169927. doi: 10.1172/jci.insight.169927.
PubMed 39513363
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study Testing the Effects of BTK Inhibitor Ibrutinib on Levels and Function of Myeloid Derived Suppressor Cells and Other Immune Subsets in Patients With Metastatic Solid Tumors
- ClinicalTrials.gov ID
- NCT03525925
- Acronym / sponsor ID
- OSU-18015
- Conditions
- Metastatic Malignant Solid Neoplasm
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Ohio State University Comprehensive Cancer CenterUniversity, hospital or other
- Study start
- 18 Jul 2018 (actual)
- Primary completion
- 20 Feb 2020 (actual)
- Study completion
- 31 Jul 2022 (actual)
- First posted
- 16 May 2018 (actual)
- 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 phase I trial studies how well ibrutinib and nivolumab work in treating participants with solid tumors that have spread to other places in the body. Ibrutinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as nivolumab, may interfere with the ability of tumor cells to grow and spread. Giving ibrutinib and nivolumab may work better in treating participants with solid tumors.
Detailed description
PRIMARY OBJECTIVES:
- Evaluate the effect of the ibrutinib therapy on circulating levels of myeloid derived suppressor cells MDSC.
SECONDARY OBJECTIVES:
- Assess safety of the study combination in study subjects.
EXPLORATORY OBJECTIVES:
- Evaluate the effect of the ibrutinib/nivolumab therapy on circulating levels of MDSC.
II. Evaluate the effect of the ibrutinib and ibrutinib/nivolumab therapy on the immunosuppressive function of circulating MDSC by measuring their ability to inhibit T cell proliferation and natural killer cell mediated antibody dependent cell cytotoxicity.
III. Study the effect of ibrutinib and ibrutinib/nivolumab therapy on levels of circulating innate and adaptive immune cells such as natural killer cell and T lymphocyte subsets.
IV. Study circulating MDSC levels at the time of disease progression. V. Evaluate in a preliminary fashion the effect of the regimen on progression-free survival.
OUTLINE:
Participants receive ibrutinib orally (PO) daily for 15 days. After 7 days receiving ibrutinib, participants receive nivolumab intravenously (IV) over 60 minutes on days 1 and 15. Courses with nivolumab repeat every 28 days in the absence of disease progression or unaccepted toxicity.
After completion of study treatment, participants are followed up every 3 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (ibrutinib, nivolumab) | Experimental | Drug: Ibrutinib, Other: Laboratory Biomarker Analysis, Biological: NivolumabParticipants receive ibrutinib PO daily for 15 days. After 7 days receiving ibrutinib, participants receive nivolumab IV over 60 minutes on days 1 and 15. Courses with nivolumab repeat every 28 days in the absence of disease progression or unaccepted toxicity. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (15 listed)
- Patients with biopsy-proven metastatic solid tumor and be eligible to receive nivolumab per standard of care
- Patients will be allowed to have any number of prior lines of therapy for metastatic cancer
- Patients with measurable and non-measurable disease are allowed to participate
- Absolute neutrophil count (ANC) ? 1.5 x 10^3/mm^3
- Hemoglobin (Hgb) ? 9 g/dL
Key exclusion criteria (20 listed)
- History of prior therapy with ibrutinib or nivolumab
- Unable to swallow capsules or having disease that is significantly affecting gastrointestinal function and/or inhibiting small intestine absorption
- Diagnosis of congenital or acquired immunodeficiency with the exception of chemotherapy induced immune suppression
- Active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids of greater than or equal to prednisone 10 mg/day or other immunosuppressive agents; patients with history of adequately treated Hashimoto?s thyroiditis will be eligible; patients requiring a short course of a high dose prednisone burst to treat asthma or common obstructive pulmonary disease will also be eligible 5 days following completion of the prednisone treatment
- Use of systemic steroids at a dose above 10 mg/day of prednisone or prednisone equivalent in cycle 1 of study therapy; systemic steroids must be discontinued at least 5 days prior to initiating study therapy; exception will be given to patients who develop immune related adverse events that necessitate use of steroids or other immune suppressive agents; following cycle 1 of study treatment, the use of systemic steroids will be allowed per discretion of the treating physician
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 |
|---|---|---|
| IbrutinibAlso: BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765Given PO | Drug | Treatment (ibrutinib, nivolumab) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (ibrutinib, nivolumab) |
| NivolumabAlso: BMS-936558, MDX-1106, NIVO, ONO-4538Given IV | Biological | Treatment (ibrutinib, nivolumab) |
Primary outcome
Circulating levels of myeloid derived suppressor cells
Time frame: Up to 2 years
Will be summarized using descriptive statistics (N, mean, standard deviation, median, minimum, and maximum) and/or frequency and percentages for medically relevant categories. Changes of the continuous variables will be estimated using mixed model for repeated measures with proper data transformation as needed, and two-way tables and Chi-Square test will be used to summarize the changes of the categorical data.
2 secondary outcomes
Incidence of adverse events
Time frame: Up to 2 years
Progression free survival
Time frame: Interval from study enrollment to first documented disease progression according to Response Evaluation Criteria in Solid Tumors 1.1 or death from any cause (whichever occurs first), assessed at 1 year
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 18 Mar 2024.
- Derived from this study: PubMed 39513363Schwarz E, Benner B, Wesolowski R, Quiroga D, Good L, Sun SH, Savardekar H, Li J, Jung KJ, Duggan MC, Lapurga G, Shaffer J, Scarberry L, Konda B, Verschraegen C, Kendra K, Shah M, Rupert R, Monk P, Shah HA, Noonan AM, Bixel K, Hays J, Wei L, Pan X, Behbehani G, Hu Y, Elemento O, Chung D, Xin G, Blaser BW, Carson WE 3rd. Inhibition of Bruton's tyrosine kinase with PD-1 blockade modulates T cell activation in solid tumors. JCI Insight. 2024 Nov 8;9(21):e169927. doi: 10.1172/jci.insight.169927.
- The JameslineLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Robert Wesolowski, MD principal investigator
Ohio State University Comprehensive 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 Ibrutinib, Laboratory Biomarker Analysis and Nivolumab in people with Metastatic Malignant Solid Neoplasm, run by Ohio State University Comprehensive 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 15 inclusion and 20 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 18 Mar 2024. 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?
Circulating levels of myeloid derived suppressor cells (time frame: Up to 2 years). 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 NCT03525925, 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 18 Mar 2024.