STR + Anti PD-1 Therapy in Patients with Locally Advanced Unresectable Pancreatic Adenocarcinoma

NCT04098432 | Completed Phase 1

• 1 other identifier: CA209- 9KH
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 4

Brief Summary

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

Conditions

Locally Advanced Unresectable Pancreatic Adenocarcinoma

Keywords

Stereotactic radiotherapy; Nivolumab; Anti PD-1; Pancreatic cancer; Pancreatic Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• Progression free survival

  Through study completion, an average of 4 years

• Overall survival

  Through study completion, an average of 4 years

• Relationship of laboratory markers and progression

  Through study completion, an average of 4 years

• patient's capacity to fulfill the activities of daily living and quality of life

  Through study completion, an average of 4 years

Study Arms (1)

Arm 1

EXPERIMENTAL

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

Drug: Nivolumab; Radiation: Stereotactic radiotherapy

Interventions

Nivolumab DRUG

Nivolumab 3 mg/kg intravenously every two weeks untill disease progression or unacceptable toxicity

Also known as: Opdivo

Arm 1

Stereotactic radiotherapy RADIATION

The prescribed dose will be 32 Gy in four fractions in four weeks (8 Gy per one fraction).

Also known as: Radiation

Arm 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 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

Sponsors & Collaborators

• University Hospital Hradec Kralove: lead
• Bristol-Myers Squibb: collaborator
• GCP-Service International s.r.o.: collaborator

Study Sites (4)

Klinika Onkologie a radioterapie, Fakultní nemocnice Hradec Králové

Hradec Králové, 50005, Czechia

Location

Onkologická klinika, Fakultní nemocnice Olomouc

Olomouc, 77900, Czechia

Location

Onkologická klinika, Thomayerova nemocnice

Prague, 14059, Czechia

Location

Ústav radiační onkologie, Nemocnice Na Bulovce

Prague, 18081, Czechia

Location

Related Publications (1)

• Vosmik M, John S, Dvorak J, Mohelnikova-Duchonova B, Melichar B, Lohynska R, Ryska A, Banni AM, Krempova J, Sirak I. Stereotactic Radiotherapy Plus Nivolumab in Patients with Locally Advanced Pancreatic Cancer: Results from Phase 1/2 Clinical CA209-9KH Trial. Oncol Ther. 2024 Dec;12(4):817-831. doi: 10.1007/s40487-024-00309-z. Epub 2024 Oct 23.

  PMID: 39441483 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Nivolumab; Radiosurgery; Radiation

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques; Physical Phenomena

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2019
• First Posted: September 23, 2019
• Study Start: December 3, 2018
• Primary Completion: September 30, 2022
• Study Completion: September 30, 2022
• Last Updated: September 23, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (4)