Table 2.

Clinical trials on ILs and breast cancer bone metastases.

Trial Number and Status	Aim of the Trial	Trial Arms	Interleukin(s) Identified and Dosage	Function of Interleukin(s)	Summary of Main Trial Findings
NCT00006228 Completed	Study the effectiveness of trastuzumab + IL-2 in patients with metastatic breast cancer that did not respond to trastuzumab therapy alone.	Trastuzumab IV and aldesleukin SC.	IL-2 Trastuzumab over 30–90 min on days 1 and 8 and aldesleukin on days 2–7 and 9–21. Beginning on day 22, trastuzumab over 30 min every 14 days and aldesleukin daily on days 1–14. Treatment continues for 1 year.	IL-2 may stimulate patients white blood cells to kill breast cancer cells.	No results posted
NCT00001269 Completed	Determine the maximal tolerated dose of IL-3 given alone or sequentially with GM-CSF following FLAC CT in metastatic breast cancer patients.	IL-3 alone or sequentially with GM-CSF.	IL-3 Dosage not reported.	IL-3 and GM-CSF may ameliorate cumulative thrombocytopenia after FLAC CT.	No results posted
NCT00004893 Completed	Determine the activity of IL-12 as defined by the % of patients who did not progress after 6 months of therapy.	Arm I: Patients begin therapy no sooner than 3 and no later than 6 weeks since last CT dose and receive IL-12 SC twice a week. Patients are followed every 3 months for 1 year, and, if no progression, for 5 yrs. Arm II: Patients are observed for 6 months and, if disease progresses or not, they may receive IL-12 as in arm I. Patients are followed for toxicity until IL-12 is discontinued.	IL-12 Dosage not reported.	IL-12 may kill tumor cells by stopping blood flow to the tumor and by stimulating patients white blood cells to kill breast cancer cells.	No results posted
NCT00003412 Study completion date passed, and status not verified in more than 2 years	Study the effectiveness of IL-12 in women with metastatic breast cancer who have received high-dose CT, and peripheral stem cell transplantation.	Arms not reported.	IL-12 Dosage not reported.	IL-12 may kill tumor cells by stopping blood flow to the tumor and by stimulating patients white blood cells to kill breast cancer cells.	No results posted
NCT00849459 Completed	Determine toxicity and maximum tolerated dose of intratumoral injection of ADV-hIL12 gene in women with metastatic breast cancer.	ADV-hIL12	IL-12 Starting dose of ADV-hIL12 to 1 × 10 to the 10th power vp per patient, escalation in half-log increments up to 1 × 10 to the 13th power vp per patient, dose escalation at lower increments of 2 × 10 to a maximum of 3.0 × 10 to the 13th power vp per patient.	Placing the gene for IL-12 into breast cancer cells may help the body build an immune response to kill tumor cells.	No results posted
NCT00002616 Study completion date passed, and status not verified in more than 2 years	Study the effectiveness of IL-2 + G-CSF to stimulate cell production in patients with stage IIIB, stage IV, metastatic, or recurrent breast cancer to undergo peripheral stem-cell transplantation.	Arm I: G-CSF for priming and following stem cell transplant. Arm II: G-CSF for priming and G-CSF + IL-2 following transplant. Arm III: G-CSF + IL-2 for priming and G-CSF following transplant. Arm IV: G-CSF + IL-2 for priming and following transplant. Cohorts of 3–6 patients each treated on each arm and at escalating doses of IL-2.	IL-2 Dosage not specified.	Estimate the maximum tolerated dose of continuous infusion IL-2 combined with a dose of G-CSF to stimulate PBSC for harvest in patients with advanced breast cancer.	No results posted
NCT00001270 Completed	Define the toxicity of IL-1 administered for 7 days prior to ICE CT.	Arms not reported.	IL-1 Dosage not specified.	IL-1 toxicity.	No results posted
NCT01368107 Completed	Evaluate the impact of an immunotherapy by IL-7 on CD4 lymphopenia (CYT107), risks of severe hematological toxicity and tumor progression in metastatic breast cancer patients.	Arm I: Placebo comparator; Arm II: CYT107 SC before CT; Arm III: CYT107 during CT; Arm IV: CYT107 before and during CT.	IL-7 Arm I: Placebo before the 1st (D0, D7, D14) and during the 3rd CT cycle (D57, D64, D71); Arm II: CYT107 (10 µg/kg/week for 3 weeks) before the 1st cycle and placebo during the 3rd cycle; Arm III: placebo before the 1st cycle and CYT107 during the 3rd cycle; Arm IV: CYT107 before the 1st cycle and IL-7 (10µg/kg/week SC for 3 weeks) during the 3rd cycle.	Immunotherapy by IL-7 on CD4 lymphopenia.	No results posted
NCT02627274 Recruiting	Evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of RO6874281, an immunocytokine consisting of IL-2v targeting FAP, as single agent or in combination with trastuzumab or cetuximab.	Arm I: RO6874281 monotherapy; Arm II: RO6874281 + trastuzumab; Arm III: RO6874281 + cetuximab.	IL-2v Arm I: 5 mg of RO6874281 as single agent OW; Arm II: 10 mg of RO6874281 + trastuzumab (loading dose 4 mg/kg and maintenance dose 2 mg/kg from cycle 2) OW; Arm III: 5 mg of RO6874281 + cetuximab (loading dose 400 mg/m2 and maintenance dose 250 mg/m2 from cycle 2) OW.	Not specified	Not applicable
NCT00002780 Unknown	Evaluate the toxicities of low-dose IL-2 and GM-CSF, and multiple doses of activated T-cells following PBSC transplantation in women with stage IIIB or metastatic adenocarcinoma of the breast.	Patients receive GM-CSF SC daily for 5 days prior to PBSC collection or for 2 days prior to bone marrow harvest. Following collection, patients receive high dose CT on days −6 and −3. Patients undergo PBSC transplantation on day 0. Following transplantation, patients receive multiple doses of monoclonal antibody OKT3 activated T lymphocytes IV between days 1 and 65, continuous low dose IL-2 IV over days 1–65, and GM-CSF on days 5–21.	IL-2 Dosage not specified.	Evaluate if T-cells and IL-2 combined with PBSC transplantation or bone marrow transplantation in women who have stage IIIB or metastatic breast cancer may kill more tumor cells.	No results posted
NCT03135171 Recruiting	Determine the highest dose level of anti-IL-6R (tocilizumab) that, when given in combination with trastuzumab and pertuzumab every 3 weeks in subjects with HER2-positive metastatic breast cancer, results in less than 25% incidence of dose limiting toxicity.	Trastuzumab, pertuzumab, and tocilizumab.	Anti-IL-6R Trastuzumab: all dose levels receive 8 mg/kg loading dose for cycle 1 and 6 mg/kg in subsequent cycles, every 3 weeks. Pertuzumab: dose levels 2 and 3 receive 840 mg loading dose for cycle 1 and 420 mg in subsequent cycles, every 3 weeks. Tocilizumab: 4–8 mg/kg administered IV every 3 weeks.	Safety, tolerability, and recommended phase 2 dose of tocilizumab.	No results posted

Abbreviation: IL = interleukin; IV = intravenously; SC = subcutaneously; GM-CSF = granulocyte macrophage colony-stimulating factor; FLAC = fluorouracil, leucovorin, adriamycin, cytoxan; CT = chemotherapy; ADV-hIL12 = adenovirus-mediated human interleukin 12; vp = virus particles; G-CSF = granulocyte colony-stimulating factor; PBSC = peripheral blood stem cells; ICE = ifosfamide, carboplatin, etoposide; IL-2v = interleukin-2 variant; FAP = fibroblast activation protein; HER2 = human epidermal growth factor receptor 2; OW = once weekly.