Clinical Trials /

Siltuximab and Spartalizumab in Patients With Metastatic Pancreatic Cancer

NCT04191421

Description:

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 patients 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.

Related Conditions:
  • Pancreatic Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Siltuximab and Spartalizumab in Patients With Metastatic Pancreatic Cancer
  • Official Title: A Phase Ib/II Trial of Siltuximab and Spartalizumab in Metastatic Pancreatic Cancer

Clinical Trial IDs

  • ORG STUDY ID: IRB00105616
  • SECONDARY ID: NCI-2018-01793
  • SECONDARY ID: Winship4463-18
  • NCT ID: NCT04191421

Conditions

  • Metastatic Pancreatic Adenocarcinoma
  • Stage IV Pancreatic Cancer AJCC v8

Interventions

DrugSynonymsArms
SiltuximabAnti-IL-6 Chimeric Monoclonal Antibody, cCLB8, CNTO 328, SylvantTreatment spartalizumab and siltuximab Phase I dose level 1
SpartalizumabPDR001Treatment spartalizumab and siltuximab Phase I dose level 1

Purpose

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 patients 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.

Detailed Description

      PRIMARY OBJECTIVE:

      I. Determine the recommended phase II dose for the combination of spartalizumab and
      siltuximab.

      SECONDARY OBJECTIVES:

      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.

      EXPLORATORY OBJECTIVE:

      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. Cycles 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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment spartalizumab and siltuximab Phase I dose level 1ExperimentalArm 1 (Phase I dose level 1) Participants receive spartalizumab 300 mg IV over 30 minutes on day 1 and siltuximab 6 mg/Kg IV over 1 hour on day 1. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
  • Siltuximab
  • Spartalizumab
Treatment spartalizumab and siltuximab Phase I level 2ExperimentalArm 2 (Phase I dose level 2) Participants receive spartalizumab 300 mg IV over 30 minutes on day 1 and siltuximab 11 mg/Kg IV over 1 hour on day 1. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
  • Siltuximab
  • Spartalizumab
Treatment spartalizumab and siltuximab phase I level 2aExperimentalArm 3 (Phase I dose level 2a) Participants receive spartalizumab 300 mg IV over 30 minutes on day 1 and siltuximab 9 mg/Kg IV over 1 hour on day 1. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
  • Siltuximab
  • Spartalizumab
Treatment spartalizumab and siltuximab phase IIExperimentalArm 4 (Phase II ) Participants receive spartalizumab 300 mg IV over 30 minutes on day 1 and siltuximab at dose determined in Arm 1 to 3 IV over 1 hour on day 1. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
  • Siltuximab
  • Spartalizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Cytological or histologic diagnosis and metastatic pancreatic adenocarcinoma disease
             that has failed at least one standard regimen such as gemcitabine nab-paclitaxel or
             folinic acid, fluorouracil, irinotecan hydrochloride, and oxaliplatin (FOLFIRINOX).

          -  Patient must meet the following laboratory values at the screening visit:

               -  Absolute neutrophil count ≥ 1.5 x 109/L

               -  Platelets ≥ 75 x 109/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 ULN

               -  Aspartate transaminase (AST) ≤ 2.5 x ULN, except for patients with liver
                  metastasis, who may only be included if AST ≤ 5.0 x upper limit of normal (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 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 ECG defined as the following:

          -  Resting heart rate 50-90 bpm

          -  QT corrected for HR using Fridericia's method (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 (β-human chorionic
             gonadotropin [β-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 3 months 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.

        Exclusion Criteria:

          -  Prior exposure to agents targeting programmed cell death protein-1 (PD-1), PD-L1, IL-6
             or the IL-6 receptor. Prior chemotherapy is allowed as long as adequate washout period
             of ≥ 4 weeks.

          -  Any untreated central nervous system (CNS) lesion. However, patients are eligible if:
             a) all known CNS lesions have been treated with radiotherapy or surgery and b) patient
             remained without evidence of CNS disease progression ≥ 4 weeks after treatment and c)
             patients must be off corticosteroid therapy for ≥ 2 weeks.

          -  Use of any live vaccines against infectious diseases within 4 weeks of initiation of
             study treatment.

          -  Systemic chronic steroid therapy (≥ 10mg/day prednisone or equivalent) or any
             immunosuppressive therapy 7 days prior to planned date of first dose of study
             treatment. Note: Topical, inhaled, nasal and ophthalmic steroids are allowed.

          -  Active, known or suspected autoimmune disease or a documented history of autoimmune
             disease Note: Patients with vitiligo, controlled type I diabetes mellitus on stable
             insulin dose, residual autoimmune-related hypothyroidism only requiring hormone
             replacement or psoriasis not requiring systemic treatment are permitted).

          -  Allogenic bone marrow or solid organ transplant.

          -  History of severe hypersensitivity reactions to other monoclonal antibodies, which in
             the opinion of the investigator may pose an increased risk of serious infusion
             reaction.

          -  Known history or current interstitial lung disease or non-infectious pneumonitis.

          -  Malignant disease, other than that being treated in this study. Exceptions to this
             exclusion include the following: malignancies that were treated curatively and have
             not recurred within 2 years prior to study treatment; completely resected basal cell
             and squamous cell skin cancers and any completely resected carcinoma in situ.

          -  Clinically significant infection, including known HIV or hepatitis C infection, or
             known hepatitis B surface antigen positivity.

          -  Clinically significant ongoing infection.

          -  Received an investigational drug (including investigational vaccines) or used an
             invasive investigational medical device within 14 days or 5 half-lives before
             enrollment (whichever is longer) or is currently enrolled in the treatment stage of an
             investigational study.

          -  A woman who is pregnant or breast-feeding, or a woman who is planning to become
             pregnant or a man who plans to father a child while enrolled in this study or within
             150 days after the last dose of study agent.

          -  Had hospitalization for infection or major surgery (eg, requiring general anesthesia)
             within 2 weeks before enrollment or have not fully recovered from surgery. Note:
             subjects with surgical procedures conducted under local anesthesia may participate.

          -  History or current diagnosis of cardiac disease indicating significant risk of safety
             for patients participating in the study such as uncontrolled or significant cardiac
             disease, including any of the following:

               -  Recent myocardial infarction (within last 6 months)

               -  Uncontrolled congestive heart failure

               -  Unstable angina (within last 6 months)

               -  Clinically significant (symptomatic) cardiac arrhythmias (e.g., sustained
                  ventricular tachycardia, and clinically significant second or third degree
                  atrioventricular block (AV) block without a pacemaker)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximal tolerated dose (MTD) of siltuximab that can be combined with spartalizumab
Time Frame:Up to 6 weeks from study start
Safety Issue:
Description:Maximal tolerated dose (MTD )is defined as the dose at which less than one-third of the subjects experience a dose-limiting toxicity (DLT) in the first 6 weeks of treatment. A DLT is defined as an adverse event or abnormal laboratory value assessed as definitely at least possibly related to study treatment treatment related that occurs within the first 6 weeks. National Cancer Institute Common Terminology Criteria for Adverse events (NCI CTCAE) version 4.03 will be used for all grading.

Secondary Outcome Measures

Measure:Overall response rate (ORR)
Time Frame:Up to 2 years from study start
Safety Issue:
Description:Overall response rate is defined as complete response (CR) + partial response (PR) in participants treated with siltuximab and spartalizumab and will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Measure:Response duration
Time Frame:From treatment start until progression or death, assessed up to 2 years
Safety Issue:
Description:Will be assessed by RECIST 1.1.
Measure:Progression-free survival
Time Frame:From treatment start until progression or death, assessed up to 2 years
Safety Issue:
Description:Will be assessed by RECIST 1.1.
Measure:Overall survival time
Time Frame:From treatment start until progression or death, assessed up to 2 years
Safety Issue:
Description:Will be assessed by RECIST 1.1.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Emory University

Last Updated

December 9, 2019