Clinical Trials /

Study of Nivolumab, Cabiralizumab, and Stereotactic Body Radiotherapy (SBRT) for Locally Advanced Unresectable Pancreatic Cancer

NCT03599362

Description:

A multi-institutional, single arm phase II study of nivolumab, cabiralizumab and stereotactic body radiotherapy (SBRT) in patients with LAUPC. The purpose of this study is to determine the safety and tolerability of combined cabiralizumab, nivolumab and radiotherapy in the treatment of locally advanced pancreatic cancer. Investigators will also estimate the surgical resection rate following treatment with combined cabiralizumab, nivolumab and radiotherapy in subjects with locally advanced unresectable pancreatic cancer.

Related Conditions:
  • Pancreatic Carcinoma
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Nivolumab, Cabiralizumab, and Stereotactic Body Radiotherapy (SBRT) for Locally Advanced Unresectable Pancreatic Cancer
  • Official Title: Nivolumab, Cabiralizumab, and Stereotactic Body Radiotherapy (SBRT) for Locally Advanced Unresectable Pancreatic Cancer

Clinical Trial IDs

  • ORG STUDY ID: 17-01430
  • NCT ID: NCT03599362

Conditions

  • Pancreatic Cancer

Interventions

DrugSynonymsArms
Nivolumab + CabiralizumabMulti Agent Chemotherapy Cancer Patients

Purpose

A multi-institutional, single arm phase II study of nivolumab, cabiralizumab and stereotactic body radiotherapy (SBRT) in patients with LAUPC. The purpose of this study is to determine the safety and tolerability of combined cabiralizumab, nivolumab and radiotherapy in the treatment of locally advanced pancreatic cancer. Investigators will also estimate the surgical resection rate following treatment with combined cabiralizumab, nivolumab and radiotherapy in subjects with locally advanced unresectable pancreatic cancer.

Trial Arms

NameTypeDescriptionInterventions
Multi Agent Chemotherapy Cancer PatientsExperimentalSubjects will be enrolled into this study following completion of 2-6 months of multi agent chemotherapy with documentation of stable or responsive disease.
  • Nivolumab + Cabiralizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically confirmed locally advanced, unresectable pancreatic cancer as defined
             by NCCN Guidelines 3.2017

          -  Locally advanced unresectable disease is defined by the NCCN as:

          -  Tumors of the head that have greater than 180 degrees of SMA encasement or any celiac
             abutment, unreconstructable SMV or portal occlusion, or aortic invasion or encasement.

          -  Tumors of the body with SMA or celiac encasement of greater than 180 degrees,
             unreconstructable SMV or portal occlusion, or aortic invasion.

          -  Tumors of the tail with SMA or celiac encasement of greater than 180 degrees.
             Irrespective of location, all tumors with evidence of nodal metastasis outside of the
             resection field are deemed unresectable.

          -  Patients must agree to pretreatment and on treatment tumor biopsy

          -  ECOG performance status of 0 or 1

          -  Completion of at least 2 months, but no more than 6 months of standard induction
             chemotherapy for LAPC, which must include either FOLFIRINOX or gemcitabine and nab-
             paclitaxel, preferably within 2-4 weeks but no longer than 8 weeks.

          -  Normal organ and marrow function as defined below:

          -  absolute neutrophil count ≥ 1,500/mm3

          -  platelets ≥ 100,000/mm3

          -  total bilirubin ≤ 1.5 x institutional upper limit of normal (except participants with
             Gilbert's syndrome who must have normal direct bilirubin)

          -  AST(SGOT) and ALT(SGPT) ≤ 2 × institutional upper limit of normal

          -  creatinine ≤ 1.5 mg/ dL OR

          -  creatinine clearance≥ 30 mL/min (as estimated by Cockcroft Gault Equation)

          -  Ability to understand and sign a written informed consent document. Participant must
             have willingness and ability to comply with scheduled visits, treatment plans,
             laboratory tests and other study procedures.

          -  Women of childbrearing potential (WOCBP) must have a negative serum or urine pregnancy
             test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to
             the start of study treatment.

          -  WOCBP must agree to follow instructions for method(s) of contraception for the
             duration of treatment with study treatment(s) and for a total of 5 months
             post-treatment completion.

          -  Males who are sexually active with WOCBP must agree to follow instructions for
             method(s) of contraception (see appendix 1) for the duration of treatment with study
             treatment(s) and for a total of 7 months posttreatment completion. In addition, male
             participants must be willing to refrain from sperm donation during this time.

        Exclusion Criteria:

          -  Resectable, borderline resectable or metastatic disease

          -  Interstitial lung disease that is symptomatic or may interfere with the detection or
             management of suspected treatment-related pulmonary toxicity.

          -  Participants with a condition requiring systemic treatment with either corticosteroids
             (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within
             14 days of study treatment administration except for adrenal replacement steroid doses
             > 10 mg daily prednisone equivalent in the absence of active autoimmune disease.

        Note: Treatment with a short course of steroids (< 5 days) up to 7 days prior to initiating
        study treatment is permitted.

          -  Current or history of clinically significant muscle disorders (eg, myositis), recent
             unresolved muscle injury, or any condition known to elevate serum CK levels

          -  Uncontrolled or significant cardiovascular disease including, but not limited to, any
             of the following:

          -  Myocardial infarction or stroke/transient ischemic attack within the past 6 months

          -  Uncontrolled angina within the past 3 months

          -  Any history of clinically significant arrhythmias (such as ventricular tachycardia,
             ventricular fibrillation, or torsades de pointes)

          -  History of other clinically significant heart disease (eg, cardiomyopathy, congestive
             heart failure with New York Heart Association functional classification III to IV,
             pericarditis, significant pericardial effusion, or myocarditis)

          -  Cardiovascular disease-related requirement for daily supplemental oxygen therapy.

          -  Evidence of uncontrolled, active infection, requiring parenteral anti-bacterial,
             anti-viral or anti-fungal therapy ≤ 7 days prior to administration of study
             medication.

          -  Any uncontrolled inflammatory GI disease including Crohn's Disease and ulcerative
             colitis.

          -  Participants with active, known, or suspected autoimmune disease. Participants with
             vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune
             condition only requiring hormone replacement, euthyroid participants with a history of
             Grave's disease (participants with suspected autoimmune thyroid disorders must be
             negative for thyroglobulin and thyroid peroxidase antibodies and thyroid stimulating
             immunoglobulin prior to first dose of study treatment), psoriasis not requiring
             systemic treatment, or conditions not expected to recur in the absence of an external
             trigger are permitted to enroll after discussing with the Principal Investigator.

          -  Concomitant use of statins while on study. However, a patient using statins for over 3
             months prior to study drug administration and in stable status without CK rise may be
             permitted to enroll.

          -  Non-oncology vaccine therapies for prevention of infectious diseases (eg, human
             papillomay virus vaccine) within 4 weeks of study drug administration. The inactivated
             seasonal influenza vaccine can be given to patients before treatment and while on
             therapy without restriction. Influenza vaccines containing live virus or other
             clinically indicated vaccinations for infectious diseases (ie, pneumovax, varicella,
             etc) may be permitted, but must be discussed with the principal investigator and may
             require a study drug washout period prior to and after administration of vaccine.

          -  Known human immunodeficiency virus (HIV), known active hepatitis A, or known hepatitis
             B or C infection.

          -  History of acute diverticulitis within the last 6 months, or current chronic diarrhea

          -  Pregnant or lactating women.

          -  Women of childbearing potential (WOCBP) with either a positive or no pregnancy test
             (serum or urine) at baseline. (Postmenopausal women must have been amenorrheic for at
             least 12 months to be considered of non-childbearing potential.)

          -  WOCBP who are unwilling or unable to use an acceptable method to minimize the risk of
             pregnancy (see appendix 1) for the entire study period and for at least 5 months after
             the last dose of investigational product. WOCBP who are continuously not
             heterosexually active are also exempt from contraceptive requirements, but still must
             undergo pregnancy testing as described in section - Sexually active fertile men not
             using effective birth control if their partners are WOCBP

          -  History of primary immunodeficiency.

          -  History of organ allograft or allogeneic bone marrow transplant.

          -  Any prior radiation therapy, immunotherapy, or biologic ('targeted') therapy for
             treatment of the patient's pancreatic tumor. Patient should have received either
             FOLFIRINOX or gemcitabine and nab-paclitaxel prior to enrollment.

          -  Treatment for other invasive carcinomas within the last five years who are at greater
             than 5% risk of recurrence at time of eligibility screening. Carcinoma in-situ and
             basal cell carcinoma/ squamous cell carcinoma of the skin are allowed.

          -  Participation in any investigational drug study within 4 weeks preceding the start of
             study treatment.

          -  Major surgery, excluding laparoscopy, within 4 weeks of the start of study treatment,
             without complete recovery.

          -  History of allergy to study treatments or any of its components

          -  Known history of sensitivity to infusions containing Tween 20 (polysorbate 20) and
             Tween 80 (polysorbate 80)
      
Maximum Eligible Age:100 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Measure of safety of combined cabiralizumab, nivolumab and radiotherapy in the treatment of locally advanced pancreatic cancer measured by unacceptable toxicity
Time Frame:24 Months
Safety Issue:
Description:Grade 3 fatigue lasting > 2 Weeks Grade 3 Nausea lasting > 7 days despite maximal medical management Grade 3 or more anorexia Grade 3 or more vomiting Grade 3 or more diarrhea Grade 3 or more pancreatitis Grade 3 abdominal pain Grade 3 or more radiation dermatitis Grade 3 or more GI hemorrhage Grade 3 or more GI fistula Grade 3 or more GI stenosis Grade 3 or more GI perforation

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:NYU Langone Health

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