Stereotactic Radiotherapy + Anti PD-1 Therapy in Patients With Locally Advanced Unresectable Pancreatic Adenocarcinoma (CA209-9KH)

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

Study Overview

• Status: Completed
• Conditions: Locally Advanced Unresectable Pancreatic Adenocarcinoma
• Intervention / Treatment: Drug: Nivolumab; Radiation: Stereotactic radiotherapy

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

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Czechia
  • Hradec Králové, Czechia, 50005
    • Klinika onkologie a radioterapie, Fakultni Nemocnice Hradec Kralove
  • Olomouc, Czechia, 77900
    • Onkologicka klinika, Fakultni Nemocnice Olomouc
  • Praha, Czechia, 14059
    • Onkologická klinika, Thomayerova nemocnice
  • Praha, Czechia, 18081
    • Ústav radiační onkologie, Nemocnice Na Bulovce

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; 4-weeks stereotactic radiotherapy followed by nivolumab 3 mg/kg every two weeks	Drug: Nivolumab; Nivolumab 3 mg/kg intravenously every two weeks untill disease progression or unacceptable toxicity; Other Names: Opdivo; Radiation: Stereotactic radiotherapy; The prescribed dose will be 32 Gy in four fractions in four weeks (8 Gy per one fraction).; Other Names: Radiation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety - incidence of treatment-related adverse events	Measured by the incidence of adverse events (AEs), serious adverse events (SAEs), deaths	Through study completion, an average of 4 years
Safety - incidence of laboratory abnormalities	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)	Through study completion, an average of 4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	To evaluate progression free survival (median of progression free survival and 1-, 2-year progression free survival)	Through study completion, an average of 4 years
Overall survival	To evaluate overall survival (median of overall survival and 1-, 2-year overall survival)	Through study completion, an average of 4 years
Relationship of laboratory markers and progression	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)	Through study completion, an average of 4 years
patient's capacity to fulfill the activities of daily living and quality of life	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).	Through study completion, an average of 4 years

Collaborators and Investigators

• Sponsor: University Hospital Hradec Kralove
• Collaborators: Bristol-Myers Squibb; GCP-Service International s.r.o.

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2018
• Primary Completion (Actual): September 30, 2022
• Study Completion (Actual): September 30, 2022

Study Registration Dates

• First Submitted: March 6, 2019
• First Submitted That Met QC Criteria: September 18, 2019
• First Posted (Actual): September 23, 2019

Study Record Updates

• Last Update Posted (Actual): July 10, 2023
• Last Update Submitted That Met QC Criteria: July 7, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Nivolumab; Pancreatic cancer; Pancreatic Adenocarcinoma; Stereotactic radiotherapy; Anti PD-1
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: CA209- 9KH

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No