Particle-based Partial Tumor Irradiation of Unresectable Bulky Tumors

Studien-Informationen Einschlusskriterien Studien-Rationale Studien-Arme Geprüfte Regime

Rekrutierend

NCT-Nummer:
NCT04875871

Studienbeginn:
November 2021

Letztes Update:
20.03.2024

Wirkstoff:
-

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
EBG MedAustron GmbH

Collaborator:
Medical University of Vienna, Landesklinkum Wiener Neustadt, Klinik Ottakring,

Studienleiter

Slavisa Tubin, M.D.
Principal Investigator
EBG MedAustron

Kontakt

Slavisa Tubin, M.D.
Kontakt:
Phone: +43 2622 26 100
Phone (ext.): 401
E-Mail: slavisa.tubin@medaustron.at» Kontaktdaten anzeigen

Eugen B. Hug, Univ. Prof.
Kontakt:
Phone: +43 2622 26 100
Phone (ext.): 102
E-Mail: eugen.hug@medaustron.at» Kontaktdaten anzeigen

Studienlocations
(1 von 1)

EBG MedAustron GmbH
2700 Wiener Neustadt
AustriaRekrutierend» Google-Maps
Ansprechpartner:
Slavisa Tubin, M.D.
Phone: +43 2622 26 100
Phone (ext.): 401
E-Mail: slavisa.tubin@medaustron.at» Ansprechpartner anzeigen

Studien-Informationen

Detailed Description:

This is a mono-centric, prospective, two-arms, feasibility study in which the investigator

will enroll up to 22 patients with locally advanced or metastatic cancers with at least one

bulky (≥6cm) lesion. This study uses a novel, recently developed unconventional radiotherapy

technique, consisting of a short course (3 fractions) high dose partial irradiation targeting

exclusively the hypoxic segment of unresectable bulky tumors while sparing the peritumoral

immune microenvironment for induction of immune-mediated tumoricidal bystander and abscopal

effects.

The present study will explore the potential biological and physical advantages of

particle-based radiotherapy to deliver a highly conformal radiation dose to the hypoxic tumor

segment defined by using hypoxia-specific Copper-64-Diacetyl-bis (N4-methylthiosemicarbazone)

Positron Emission Tomography-Computer Tomography (64Cu-ATSM PET-CT) and dynamic contrast

enhanced Magnetic Resonance Tomography imaging. Based on tumor location, volume and risk

factors related to nearby organs at risk, patients will be divided in the "high-dose" or

"reduced-dose" group which will be treated with different dose-schedules according to risk

factors.

Additionally, radiotherapy will be administered at the precise timing, determined

individually for each patient, based on the serially mapped homeostatic immune fluctuations

by monitoring blood levels of the inflammatory markers. The objective is to synchronize the

radiation treatment with the favorable, most reactive anti-tumor immune response phase, in

order to break tumor´s immune-tolerance locally and systemically.

Ein-/Ausschlusskriterien

Inclusion Criteria:

1. Written informed consent obtained from the patient prior to performing any

treatment-related procedures.

2. Biopsy proven malignant unresectable solid bulky primary or recurrent tumor (diameter

of at least 6 cm or greater, except for the Central Nervous System (CNS) tumors), or

in a case of lack of recent biopsy progression on at least two consecutive

radiological examinations, with biopsy proof in the past. Presence of locally advanced

(cN+) and/or metastatic disease will be accepted in order to allow for assessment of

the abscopal effects.

3. Ineligibility for standard treatments including surgery, conventional (whole tumor)

radiotherapy and systemic therapy, or being in progression or stable (with no response

to systemic treatment) under systemic therapy.

4. A minimum time interval from last dose of systemic therapy before radiotherapy of two

weeks; Systemic therapy may be resumed 4 weeks following radiotherapy in order to

permit assessment of the treatment efficacy.

5. Median life expectancy of >2 months.

6. Age > 18 years.

7. Adequate bone marrow function as follows below: Haemoglobin ≥ 8.0 g/d; Absolute

neutrophil count (ANC) ≥ 1.5 x 10ꝰ/L (> 1500 per mm3); Platelet count ≥ 100 x 10ꝰ/L

(>100,000 per mm3).

8. Female patients must either be of non-reproductive potential (i.e. post-menopausal by

history: ≥60 years old and no menses for ≥1 year without an alternative medical cause;

OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of

bilateral oophorectomy) OR women of fertile age must have adequate conception

prevention measures and must have a negative serum pregnancy test upon study entry.

9. Patient is willing and able to comply with the follow up including scheduled visits

and examinations.

Exclusion Criteria:

1. Patients without bulky lesions.

2. Tumors suitable for the standard therapies including surgery, conventional (whole

tumor) irradiation and systemic therapies.

3. Median life expectancy of less than 2 months.

4. Contraindication to i.v. Computer Tomography and Magnetic Resonance Tomography

contrast medium administration, particularly estimated glomerular filtration rate

(GFR) less than 45 mL/min/1.73 m2.

5. History of autoimmune disease.

6. Current or prior use of immunosuppressive medication within 14 days before enrollment

with the exceptions of intranasal and inhaled corticosteroids or systemic

corticosteroids at physiological doses, which are not to exceed 10 mg/day of

prednisone, or an equivalent corticosteroid.

7. History of primary immunodeficiency.

8. History of allogeneic organ transplant.

9. Uncontrolled intercurrent comorbidity including, but not limited to, ongoing or active

infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable

angina pectoris, active bleeding diatheses including any patient known to have

evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus

(HIV), or psychiatric illness/social situations that would limit compliance with study

requirements or compromise the ability of the patient to give written informed

consent.

10. Female patients who are pregnant, breast-feeding or male or female patients of

reproductive potential who are not employing an effective method of birth control.

11. Any condition that, in the opinion of the investigator, would interfere with

evaluation of study treatment or interpretation of patient safety or study results.

(Note: criterion will be evaluated on the four eyes principle, evaluated by both

Principle Investigator and Sub-Investigators.)

12. Patients with uncontrolled seizures.

Studien-Rationale

Primary outcome:

1. Bystander (local) tumor response rate (Time Frame - 11 months (after treatment)):
Bystander (local, at the level of the partially treated bulky tumor) response rate defined as at least a 30% regression of the unirradiated tumor tissue.

Secondary outcome:

1. Feasibility of PARTICLE-PATHY (Time Frame - 3,5 years (recruiting time + treatment time + 11 months follow-up)):
Feasibility of patient recruitment, treatment and follow-up rates.

2. Overall survival (Time Frame - 11 months (after treatment)):
Defined as the time from treatment until the time of death from any cause.

3. Time to local tumor progression (Time Frame - 11 months (after treatment)):
Defined as the time from treatment until the time of local disease progression.

4. Time to distant tumor progression (Time Frame - 11 months (after treatment)):
Defined as the time from treatment until the time of distant disease progression.

5. Abscopal (distant) tumor response rate (Time Frame - 11 months (after treatment)):
Defined as the proportion of metastatic patients that exhibited an abscopal effect versus the total number of metastatic patients allocated to the treatment.

6. Symptoms relief (Time Frame - 11 months (after treatment)):
Proportion of patients who will achieve a partial or complete relief at different time-points.

7. Radiation related toxicity (Time Frame - 11 months (after treatment)):
Toxicity assessment according to NCI CTCAE v5.0

8. Feasibility of timing of PARTICLE-PATHY and its relation to clinical outcomes (Time Frame - Until 11 months after treatment):
The feasibility of PARTICLE-PATHY and to it related TIMING will be defined by the proportion of patients allocated to this treatment who received it within dosimetric constraints after being able to define the immune-cycle periodicity and to synchronize radiotherapy with it versus the total number of patients allocated to the treatment.

9. Bystander/abscopal response rate in relation to dose-size of Peritumoral Immune Microenvironment (PIM) (Time Frame - 11 months (after treatment)):
See title

10. Bystander/abscopal response rate in relation to Interleukin-2 and Interferon Gamma values (Time Frame - 11 months (after treatment)):
Two key cytokines, Interleukin-2 (IL-2) and Interferon Gamma (INFg), will be serially assessed at baseline and after each radiotherapy treatment, in order to determine their potential role in modulating the immune response in relation to the bystander/abscopal effects.

Studien-Arme

Experimental: High-dose group
3 fractions of 12 Gy Relative Biological Effectiveness (RBE)
Experimental: Reduced-dose group
3 fractions of 8-10 Gy RBE

Geprüfte Regime

Particle radiotherapy:
Partial radiotherapy targeting the hypoxic tumor segment
Magnetic resonance imaging:
For treatment planning as well as for follow-up radiological tumor assessment.
Computertomography:
For treatment planning as well as for follow-up radiological tumor assessment.
Copper-64-Diacetyl-bis (N4-methylthiosemicarbazone) Positron Emission Tomography-Computer Tomography (64Cu-ATSM-PET-CT):
For the definition of the hypoxic tumor segment in treatment planning.
18-F-FluorDesoxyGlukose Positron Emission Tomography-Computer Tomography (18F-FDG-PET-CT):
For follow-up radiological tumor assessment.
Blood sampling:
Evaluation before treatment-start, during treatment and follow-up period.

Quelle: ClinicalTrials.gov

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