Stereotactic Radiotherapy + Anti PD-1 Therapy in Patients With Locally Advanced Unresectable Pancreatic Adenocarcinoma

Overview

Stereotactic Radiotherapy + Anti PD-1 Therapy in Patients With Locally Advanced Unresectable Pancreatic Adenocarcinoma

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: September 30, 2022

Detailed Description

Phase I/II, multicentre, open label, with no control arm clinical trial of 4-weeks stereotactic radiotherapy followed by nivolumab 3 mg/kg every two weeks in adults with locally advanced pancreatic cancer who does not progress during 4 cycles of standard chemotherapy FOLFIRINOX

Interventions

  • Drug: Nivolumab
    • Nivolumab 3 mg/kg intravenously every two weeks untill disease progression or unacceptable toxicity
  • Radiation: Stereotactic radiotherapy
    • The prescribed dose will be 32 Gy in four fractions in four weeks (8 Gy per one fraction).

Arms, Groups and Cohorts

  • Experimental: Arm 1
    • 4-weeks stereotactic radiotherapy followed by nivolumab 3 mg/kg every two weeks

Clinical Trial Outcome Measures

Primary Measures

  • Safety – incidence of treatment-related adverse events
    • Time Frame: Through study completion, an average of 4 years
    • Measured by the incidence of adverse events (AEs), serious adverse events (SAEs), deaths
  • Safety – incidence of laboratory abnormalities
    • Time Frame: Through study completion, an average of 4 years
    • Biochemistry – Na (mmol/l), K (mmol/l), Cl (mmol/l), Ca (mmol/l), Ca ionized (mmol/l), Mg (mmol/l), P (mmol/l), urea (mmol/l), creatinine (µmol/l), LDH (µkat/l), AST(µkat/l), ALT(µkat/l), ALP(µkat/l), GMT(µkat/l), total bilirubin (µmol/l), conjuged bilirubin (µmol/l), total protein (g/l), albumin (g/l), fasting glucose (mmol/l), amylase (µkat/l), C-reactive protein (mg/l), endocrine panel – TSH (mU/l), Free T3 (pmol/l), Free T4 (pmol/l), hematology – complete blood count (CBC): hemoglobin (g/l), hematocrit (ratio), white blood cells (WBC) (10E9/l), red blood cells (10E12/l), platelets (10E9/l) including differential (all 10E9/l), coagulation – APTT (ratio), PT (ratio)

Secondary Measures

  • Progression free survival
    • Time Frame: Through study completion, an average of 4 years
    • To evaluate progression free survival (median of progression free survival and 1-, 2-year progression free survival)
  • Overall survival
    • Time Frame: Through study completion, an average of 4 years
    • To evaluate overall survival (median of overall survival and 1-, 2-year overall survival)
  • Relationship of laboratory markers and progression
    • Time Frame: Through study completion, an average of 4 years
    • To evaluate the relationship of laboratory markers (PD-L1 expression, tumor infiltrating lymphocytes presence, neopterin level) to progression status and time related progress of biomarkers (CEA, CA19-9)
  • patient’s capacity to fulfill the activities of daily living and quality of life
    • Time Frame: Through study completion, an average of 4 years
    • Assess by questionnaire European Organisation for Research and Treatment of Cancer (EORTC) Quality of life questionnaire (QLQ-C30) questionnaire. The EORTC QLQ-C30 comprises 30 items (i.e. single questions), 24 of which are aggregated into 9 multi-item scales, that is, 5 functioning scales (physical, role, cognitive, emotional and social), 3 symptom scales (fatigue, pain and nausea/vomiting) and one global health status scale. The remaining 6 single-item (dyspnoea, appetite loss, sleep disturbance, constipation, diarrhoea and the financial impact) scales assess symptoms.All of the scales and single-item measures range in score from 0 to 100. Higher score for the functioning scales and global health status denote a better level of functioning (i.e. a better state of the patient), while higher scores on the symptom and single-item scales indicate a higher level of symptoms (i.e. a worse state of the patient).

Participating in This Clinical Trial

Inclusion Criteria

1. Male and female patients aged ≥18 years 2. Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1 3. Locally advanced, unresectable, histologically confirmed primary adenocarcinoma of pancreas with no progression during induction chemotherapy (4 cycles of FOLFIRINOX - not a part of trial). Within screening period tumor tissue must be available and sent to the central pathological reviewer in order to confirm the diagnosis. 4. Measurable (one target lesion is sufficient) disease as per RECIST 1.1 criteria 5. Laboratory values: 1. Aspartate aminotransferase (AST) ≤ 3x ULN (upper limit of normal) 2. Alanine transaminase (ALT) ≤ 3x ULN 3. Total bilirubin ≤ 1.5 x ULN (except subjects with Gilbert syndrome who must have a total bilirubin ≤ 3x ULN) 4. Creatinine: Serum creatinine ≤ 1.5 ULN or creatinine clearance > 50ml/min (using Cockcroft/Gault formula) 5. White blood cells ≥ 2000 /ul 6. Neutrophils ≥ 1500 /ul 7. Platelets ≥ 100x 103 /ul 8. Hemoglobin ≥ 9.0 g/l 6. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study treatment. WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) and who is not postmenopausal. Menopause is defined as 12 months of amenorrhea in a woman over age 45 years in the absence of other biological or physiological causes. In addition, females under age of 55 years must have serum follicle stimulating hormone (FSH) level > 40mIU/ml to confirm menopause. Exclusion Criteria:

1. Other histology then primary pancreatic adenocarcinoma 2. Resectable disease 3. Distant metastases 4. Progressive disease during induction chemotherapy (4 cycles of FOLFIRINOX) 5. Other previous treatment of the disease except induction chemotherapy (4 cycles of FOLFIRINOX) 6. ECOG performance score of 2 or more 7. Previous therapy of malignant disease in 5 years and less before inclusion to the trial (except skin epithelial tumors) 8. Previous radiotherapy in abdominal region 9. Previous immunological treatment (anti-CTLA-4, anti-PD1 or anti-PD-L1) 10. Active, known or suspected serious autoimmune disease 11. Major surgery less than 28 days prior to the first dose of study treatment 12. Treatment of any investigational medicinal product within 4 weeks before this trial enrolment 13. Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection 14. Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency synrome (AIDS) 15. Prisoners or subjects who are involuntarily incarcerated 16. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g. infectious disease) illness

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • University Hospital Hradec Kralove
  • Collaborator
    • Bristol-Myers Squibb
  • Provider of Information About this Clinical Study
    • Sponsor

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