Siltuximab and Spartalizumab in Treating Participants with Metastatic Pancreatic Cancer
18 Years and older, Male and Female
This phase Ib/II trial studies the best dose and side effects of siltuximab and how well it works in combination with spartalizumab in treating participants with pancreatic cancer that has spread to other places in the body. Monoclonal antibodies, such as siltuximab and spartalizumab, interfere with the ability of tumors cells to grow and spread.
I. Determine the recommended phase II dose for the combination of spartalizumab and siltuximab.
I. Define the toxicity profile of the combination of the recommended phase II dose of spartalizumab and siltuximab.
II. Evaluate the activity of the combination of spartalizumab and siltuximab in previously treated patients with pancreatic cancer.
I. Evaluate the effect of the combination on the immune profile in the serum and in tumor biopsies.
OUTLINE: This is a dose-escalation study of siltuximab.
Participants receive spartalizumab intravenously (IV) over 30 minutes on day 1 and siltuximab IV over 1 hour on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, participants are followed up at 30, 60, 90, 120, and 150 days, then every 12 weeks thereafter.
- Cytological or histologic diagnosis and metastatic pancreatic adenocarcinoma disease that has failed at least one standard regimen such as gemcitabine nab-paclitaxel or fluorouracil, irinotecan hydrochloride, leucovorin calcium and oxaliplatin (FOLFIRINOX).
- Be >= 18 years of age on day of signing informed consent
- Absolute neutrophil count >= 1.5 x 10^9/L.
- Platelets >= 75 x 10^9/L.
- Hemoglobin (Hgb) >= 9 g/dL.
- Serum creatinine < 1.5 mg/dL OR creatinine clearance >= 45 mL/min using Cockcroft-Gault formula.
- Total bilirubin =< 1.5 x upper limit of normal (ULN).
- Aspartate transaminase (AST) =< 2.5 x ULN, except for patients with liver metastasis, who may only be included if AST =< 5.0 x ULN.
- Alanine transaminase (ALT) =< 2.5 x ULN, except for patients with liver metastasis, who may only be included if ALT =< 5.0 x ULN.
- Presence of measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
- Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
- Written informed consent must be obtained prior to any screening procedures.
- Normal electrocardiogram (ECG) defined as the following:
* Resting heart rate 50-90 beats per minute (bpm)
* Corrected QT interval by Fridericia's formula (QTcF) at screening < 450 ms (male patients), < 460 ms (female patients).
- Before enrollment, a woman must be either:
* Not of childbearing potential: postmenopausal (> 45 years of age with amenorrhea for at least 12 months or any age with amenorrhea for at least 6 months and a serum follicle stimulating hormone [FSH] level > 40 IU/mL); permanently sterilized (eg, tubal occlusion, hysterectomy, bilateral salpingectomy); or otherwise be incapable of pregnancy.
* Of childbearing potential and practicing (during the study and for 150 days after receiving the last dose of study agent) a highly effective method of birth control consistent with local regulations regarding the use of birth control methods for subjects participating in clinical studies: eg, established use of oral, injected or implanted hormonal methods of contraception; placement of an intrauterine device (IUD) or intrauterine system (IUS); barrier methods: condom with spermicidal foam/gel/film/cream/suppository or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository; male partner sterilization (the vasectomized partner should be the sole partner for that subject); true abstinence (when this is in line with the preferred and usual lifestyle of the subject).
* Note: If the childbearing potential changes after start of the study (eg, woman who is not heterosexually active becomes active) a woman must begin a highly effective method of birth control, as described above.
- A woman of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [beta-hCG]) or urine pregnancy test at screening.
- During the study and for 150 days after receiving the last dose of study agent, a woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction.
- A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control eg, either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, and all men must also not donate sperm during the study and for 150 days after receiving the last dose of study drug.
- Sign an informed consent document indicating that they understand the purpose of and procedures required for the study, are willing to participate in the study, and are willing and able to adhere to the prohibitions and restrictions specified in this protocol. Informed consent must be obtained before performing any study specific procedures.
Treatment Sites in Georgia
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