Safety and Blood Immune Cell Study of Anakinra Plus Physician's Chemotherapy Choice in Metastatic Breast Cancer Patients

NCT01802970 | Completed Phase 1

• 1 other identifier: 012-099
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

To determine the safety of administering anakinra plus the physician's chemotherapy choice (TPC) of nab paclitaxel, capecitabine, eribulin, or vinorelbine in patients with metastatic breast cancer (MBC), as well as determining blood immune cell transcriptional signatures in patients who undergo IL-1 receptor blockade.

Conditions

Metastatic Breast Cancer

Keywords

Anakinra; Nab Paclitaxel; Capecitabine; Eribulin; Vinorelbin

Outcome Measures

Primary Outcomes (1)

• Safety - Adverse Events in participants

  Patients will receive anakinra plus the physicians chemotherapy choice of nab paclitaxel, or capecitabine, or eribulin, or vinorelbine for metastatic breast cancer. Adverse events will be recorded throughout the trial, and regardless of the severity will be followed up by investigator until resolution is satisfactory. All adverse events and toxicities will be recorded and assessed for 30 days following the last dose of anakinra at a maximum of 6 months. Grading will be done using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.

  up to 7 months

Secondary Outcomes (1)

• To determine investigator-assessed objective response rate, clinical benefit rate, progression-free survival, and rates of chemotherapy or cancer-related anemia (HgB<10), and an anakinra-induced anti-IL-1 blood transcriptional signatures

  upto 7 months

Study Arms (1)

Anakinra plus Standard of Care

EXPERIMENTAL

Patients will undergo a 2-week run-in treatment of daily anakinra alone. This will be followed by daily anakinra (100 mg SC) plus the physician's chemotherapy ( TPC) choice of standard of care (SOC) for a maximum of 6 months.TPC choice includes nab paclitaxel (100 mg/m\^2 Intravenous on day 1,8 \&15 of a 28 day cycle), or capecitabine (1000mg/m\^2 per oral; BID choice: 14 days on, 7 days off OR 7 days on, 7 days off of a 21 day cycle), or eribulin (1.4 mg/m\^2 intravenous on day 1 \& 8 of a 21 day cycle), or vinorelbine (25mg/m\^2 on day 1,8,15 of a 28 day cycle). After 6 months, patients may continue their SOC treatment alone until disease progression or intolerable toxicity.

Drug: Anakinra plus Standard of Care

Interventions

Anakinra plus Standard of Care DRUG

Patients will undergo a 2-week run-in treatment of daily anakinra alone. This will be followed by daily anakinra (100 mg SC) plus the physician's chemotherapy ( TPC) choice of standard of care (SOC) for a maximum of 6 months.TPC choice includes nab paclitaxel (100 mg/m\^2 Intravenous on day 1,8 \&15 of a 28 day cycle), or capecitabine (1000mg/m\^2 per oral; BID choice: 14 days on, 7 days off OR 7 days on, 7 days off of a 21 day cycle), or eribulin (1.4 mg/m\^2 intravenous on day 1 \& 8 of a 21 day cycle), or vinorelbine (25mg/m\^2 on day 1,8,15 of a 28 day cycle). After 6 months, patients may continue their SOC treatment alone until disease progression or intolerable toxicity.

Also known as: Anakinra: kineret, Nab paclitaxel: Abraxane, Capecitabine: Xeloda, Eribulin: Halaven, Vinorelbine: Navelbine

Anakinra plus Standard of Care

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female or male patients ≥18 years of age.
• Histologically confirmed invasive breast cancer, locally unresectable or metastatic.
• No more than 4 prior chemotherapy regimens for metastatic disease.
• Patients currently being treated with nab paclitaxel, capecitabine,eribulin, or vinorelbine who have had a CR, PR, or SD and who have developed Grade 2, 3, or 4 fatigue on the chemotherapy are eligible for the study. It should be anticipated that these patients will continue to be treated on the same chemotherapy agent for at least 3 more months beyond the time of enrollment.
• Prior hormonal therapy in the adjuvant or metastatic setting is permitted.
• HER2-negative breast cancer. If HER2-, it is defined as follows:
• FISH-negative (FISH ratio \<2.0), or
• IHC 0-1+, or
• IHC 2+ AND FISH-negative (FISH ratio\<2.0)
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
• Adequate hematologic function, defined by:
• Absolute neutrophil count (ANC) \>1500/mm\^3
• Platelet count ≥100,000/mm\^3
• Hemoglobin \>8 g/dL
• Adequate liver function, defined by:

You may not qualify if:

• Patients with active or untreated brain metastases or meningeal metastases are ineligible. Patients who have had brain metastases resected, or have received brain radiation therapy \>4 weeks prior to study entry are eligible if they meet all of the following criteria: 1) patient has been off dexamethasone for \>2 weeks; 2) no known progression of brain metastasis.
• Previous radiotherapy for metastatic disease completed \<2 weeks prior to study treatment initiation.
• Women who are pregnant or lactating. All patients with reproductive potential must agree to use effective contraception from time of study entry until at least 3 months after the last administration of study drug.
• Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation such as: -
• severe impaired lung functions as defined as spirometry and DLCO that is 50% of the normal predicted value and/or O2 saturation that is 88% or less at rest on room air
• uncontrolled diabetes as defined by fasting serum glucose \>1.5 x ULN
• liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class C).
• History of any other disease, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug, or that might affect interpretation of the results of this study, or render the subject at high risk for treatment complications.
• Patients may not receive any other investigational treatments while participating in this study.
• Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent. Topical or inhaled corticosteroids are allowed.
• Concurrent severe, uncontrolled infection or intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements.

Sponsors & Collaborators

• Baylor Research Institute: lead

Study Sites (1)

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Interleukin 1 Receptor Antagonist Protein; Standard of Care; Capecitabine; eribulin; Vinorelbine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Officials

• Joyce O'Shaughnessy, MD

  Baylor Health Care System

  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: SPONSOR

Study Record Dates

• First Submitted: February 28, 2013
• First Posted: March 4, 2013
• Study Start: December 1, 2012
• Primary Completion: January 4, 2017
• Study Completion: January 4, 2017
• Last Updated: October 8, 2021

Record last verified: 2021-10

Locations

US (1)