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

Primary Purpose

Locally Advanced Unresectable Pancreatic Adenocarcinoma

Status
Completed
Phase
Phase 1
Locations
Czechia
Study Type
Interventional
Intervention
Nivolumab
Stereotactic radiotherapy
Sponsored by
University Hospital Hradec Kralove
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Locally Advanced Unresectable Pancreatic Adenocarcinoma focused on measuring Stereotactic radiotherapy, Nivolumab, Anti PD-1, Pancreatic cancer, Pancreatic Adenocarcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Klinika Onkologie a radioterapie, Fakultní nemocnice Hradec Králové
  • Onkologická klinika, Fakultní nemocnice Olomouc
  • Onkologická klinika, Thomayerova nemocnice
  • Ústav radiační onkologie, Nemocnice Na Bulovce

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm 1

Arm Description

4-weeks stereotactic radiotherapy followed by nivolumab 3 mg/kg every two weeks

Outcomes

Primary Outcome Measures

Safety - incidence of treatment-related adverse events
Measured by the incidence of adverse events (AEs), serious adverse events (SAEs), deaths
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)

Secondary Outcome Measures

Progression free survival
To evaluate progression free survival (median of progression free survival and 1-, 2-year progression free survival)
Overall survival
To evaluate overall survival (median of overall survival and 1-, 2-year overall survival)
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)
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).

Full Information

First Posted
March 6, 2019
Last Updated
July 7, 2023
Sponsor
University Hospital Hradec Kralove
Collaborators
Bristol-Myers Squibb, GCP-Service International s.r.o.
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1. Study Identification

Unique Protocol Identification Number
NCT04098432
Brief Title
Stereotactic Radiotherapy + Anti PD-1 Therapy in Patients With Locally Advanced Unresectable Pancreatic Adenocarcinoma
Acronym
CA209-9KH
Official Title
Stereotactic Radiotherapy + Anti PD-1 Therapy in Patients With Locally Advanced Unresectable Pancreatic Adenocarcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Completed
Study Start Date
December 3, 2018 (Actual)
Primary Completion Date
September 30, 2022 (Actual)
Study Completion Date
September 30, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital Hradec Kralove
Collaborators
Bristol-Myers Squibb, GCP-Service International s.r.o.

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Locally Advanced Unresectable Pancreatic Adenocarcinoma
Keywords
Stereotactic radiotherapy, Nivolumab, Anti PD-1, Pancreatic cancer, Pancreatic Adenocarcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm 1
Arm Type
Experimental
Arm Description
4-weeks stereotactic radiotherapy followed by nivolumab 3 mg/kg every two weeks
Intervention Type
Drug
Intervention Name(s)
Nivolumab
Other Intervention Name(s)
Opdivo
Intervention Description
Nivolumab 3 mg/kg intravenously every two weeks untill disease progression or unacceptable toxicity
Intervention Type
Radiation
Intervention Name(s)
Stereotactic radiotherapy
Other Intervention Name(s)
Radiation
Intervention Description
The prescribed dose will be 32 Gy in four fractions in four weeks (8 Gy per one fraction).
Primary Outcome Measure Information:
Title
Safety - incidence of treatment-related adverse events
Description
Measured by the incidence of adverse events (AEs), serious adverse events (SAEs), deaths
Time Frame
Through study completion, an average of 4 years
Title
Safety - incidence of laboratory abnormalities
Description
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)
Time Frame
Through study completion, an average of 4 years
Secondary Outcome Measure Information:
Title
Progression free survival
Description
To evaluate progression free survival (median of progression free survival and 1-, 2-year progression free survival)
Time Frame
Through study completion, an average of 4 years
Title
Overall survival
Description
To evaluate overall survival (median of overall survival and 1-, 2-year overall survival)
Time Frame
Through study completion, an average of 4 years
Title
Relationship of laboratory markers and progression
Description
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)
Time Frame
Through study completion, an average of 4 years
Title
patient's capacity to fulfill the activities of daily living and quality of life
Description
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).
Time Frame
Through study completion, an average of 4 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male and female patients aged ≥18 years Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1 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. Measurable (one target lesion is sufficient) disease as per RECIST 1.1 criteria Laboratory values: Aspartate aminotransferase (AST) ≤ 3x ULN (upper limit of normal) Alanine transaminase (ALT) ≤ 3x ULN Total bilirubin ≤ 1.5 x ULN (except subjects with Gilbert syndrome who must have a total bilirubin ≤ 3x ULN) Creatinine: Serum creatinine ≤ 1.5 ULN or creatinine clearance > 50ml/min (using Cockcroft/Gault formula) White blood cells ≥ 2000 /ul Neutrophils ≥ 1500 /ul Platelets ≥ 100x 103 /ul Hemoglobin ≥ 9.0 g/l 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: Other histology then primary pancreatic adenocarcinoma Resectable disease Distant metastases Progressive disease during induction chemotherapy (4 cycles of FOLFIRINOX) Other previous treatment of the disease except induction chemotherapy (4 cycles of FOLFIRINOX) ECOG performance score of 2 or more Previous therapy of malignant disease in 5 years and less before inclusion to the trial (except skin epithelial tumors) Previous radiotherapy in abdominal region Previous immunological treatment (anti-CTLA-4, anti-PD1 or anti-PD-L1) Active, known or suspected serious autoimmune disease Major surgery less than 28 days prior to the first dose of study treatment Treatment of any investigational medicinal product within 4 weeks before this trial enrolment Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency synrome (AIDS) Prisoners or subjects who are involuntarily incarcerated Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g. infectious disease) illness
Facility Information:
Facility Name
Klinika Onkologie a radioterapie, Fakultní nemocnice Hradec Králové
City
Hradec Králové
ZIP/Postal Code
50005
Country
Czechia
Facility Name
Onkologická klinika, Fakultní nemocnice Olomouc
City
Olomouc
ZIP/Postal Code
77900
Country
Czechia
Facility Name
Onkologická klinika, Thomayerova nemocnice
City
Praha
ZIP/Postal Code
14059
Country
Czechia
Facility Name
Ústav radiační onkologie, Nemocnice Na Bulovce
City
Praha
ZIP/Postal Code
18081
Country
Czechia

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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