Ibrutinib and Nivolumab in Treating Participants With Metastatic Solid Tumors

NCT03525925 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: OSU-18015NCI-2018-00423
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Metastatic Malignant Solid Neoplasm

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 2 years

Secondary Outcomes (2)

• Incidence of adverse events

  Up to 2 years

• Progression free survival

  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

Other Outcomes (1)

• Biomarker analysis

  Up to 2 years

Study Arms (1)

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.

Drug: Ibrutinib; Other: Laboratory Biomarker Analysis; Biological: Nivolumab

Interventions

Ibrutinib DRUG

Given PO

Also known as: BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765

Treatment (ibrutinib, nivolumab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (ibrutinib, nivolumab)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

Treatment (ibrutinib, nivolumab)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Ohio State University Comprehensive Cancer Center: lead

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Publications (1)

• 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.

  PMID: 39513363 DERIVED

Related Links

• The Jamesline

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

ibrutinib; Nivolumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Robert Wesolowski, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 3, 2018
• First Posted: May 16, 2018
• Study Start: July 18, 2018
• Primary Completion: February 20, 2020
• Study Completion: July 31, 2022
• Last Updated: March 18, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)