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JOURNAL ONKOLOGIE – STUDIE
SBRT-PATHY

SBRT-based PArtial Tumor Irradiation of HYpoxic Segment

Rekrutierend

NCT-Nummer:
NCT04168320

Studienbeginn:
Oktober 2018

Letztes Update:
23.02.2021

Wirkstoff:
-

Indikation (Clinical Trials):
Neoplasms

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 1

Sponsor:
Klinikum Klagenfurt am Wörthersee

Collaborator:
-

Studienleiter

Slavisa Tubin, M.D.
Principal Investigator
KABEG Klinikum Klagenfurt

Kontakt

Studienlocations
(1 von 1)

KABEG Klinikum Klagenfurt, Institute for Radiation Oncology
9020 Klagenfurt
AustriaRekrutierend» Google-Maps
Ansprechpartner:
Slavisa Tubin, M.D.
Phone: +43 463 538-0
E-Mail: slavisatubin@gmail.com
» Ansprechpartner anzeigen

Studien-Informationen

Detailed Description:

The purpose of this study is to evaluate the effectiveness of our new method for high dose

partial irradiation of the hypoxic tumor segment of bulky masses in terms of the intentional

induction of the non-targeted effects of radiotherapy in patients with metastatic or locally

advanced (N+) malignancies who are ineligible for, or currently in progression under systemic

therapies. By mapping the homeostatic immune fluctuations serially, and by monitoring the

blood levels of the cytokines and inflammatory markers over the 2 weeks prior to irradiation,

radiotherapy will be administered at the precise, optimal timing in order to stimulate and to

increase anti-tumor immune system activity.

Primary endpoint: bystander (local) and abscopal (distant, metastatic or lymph nodal sites)

response rates.

Secondary endpoints: overall safety and tolerability profile of our new radiotherapy method,

progression-free survival rates at local and distant sites, as well as overall survival

rates, efficacy of this regimen in palliating symptoms, neoadjuvant potential of this novel

radiotherapy for unresectable/borderline resectable bulky lesions, optimal timing for

radiotherapy to be administered based on the fluctuating/oscillating suppressed anti-tumor

immune response.

This monocentric, two-arm prospective phase I proof of principle trial will enroll 26

patients from a single institution: KABEG Klinikum Klagenfurt am Woerthersee, Austria.

During the visit, and after clinical examination, patients will be eligible if they satisfy

the inclusion criteria for participation in this pilot study on the use of the novel

stereotactic radiotherapy technique which will consist of partial irradiation of exclusively

hypoxic segments of their bulky tumors, with 1-3 high dose fractions of radiotherapy based on

the tumor's site, volume and its relationship with nearby organs. The irradiation will take

place within 3 weeks of clinical examination. After the treatment, the patient will be

regularly followed for the evaluation of all endpoints. If any severe toxicity (grade ≥3 per

CTCAE v 4.3 criteria) occurs in the first 7 evaluable patients, the trial will stop. Safety

reviews will continue on an ongoing basis, provided that severe toxicities do not occur in

more than 15% of patients. In the case of eventual disease progression during the follow-up,

the patients will be offered additional local (radiotherapy) or systemic (chemotherapy,

immunotherapy, hormonal therapy) treatment if indicated by current NCCN (National

Comprehensive Cancer Network) treatment recommendations and guidelines.

Routine surveillance computerized axial tomography (CT) imaging of the whole body will be

performed beginning at 1 month (+/- 3 days) after treatment to allow for endpoint assessment

- or before in any case of clinical suspicion of disease progression. Routine CT imaging

surveillance will continue per standard of care. Patients will also be followed clinically

with physical and laboratory examinations as indicated.

Tumor assessments will be completed on the CRF using RECIST v1.1. criteria. Radiographic and

clinical evaluations will be conducted with the same schedule. The investigator will assess

anti-tumor activity based on radiological assessments and clinical evaluations of patients

using RECIST v1.1 at baseline, 1 and 2 months post-treatment, and every 3 months thereafter

until confirmed disease progression per RECIST v1.1, regardless of the discontinuation of

study treatment or the initiation of subsequent anti-cancer therapy. Radiological tumor

assessments will also be conducted whenever disease progression is suspected (e.g.

symptomatic deterioration or physical examination findings suggestive of mucosal recurrence).

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Metastatic biopsy proven malignant cancer with at least one "bulky" (diameter of at

least 6 cm or greater) lesion, or in the case of a biopsy missing for any

reason-progression of the suspicious lesion evaluated on at least 2 consecutive

radiological examinations,

- Written informed consent obtained from the patient/legal representative prior to

performing any protocol-related procedures, including screening evaluation,

- Ineligibility for systemic therapy or being in progression under systemic therapy,

- A minimum time interval of four weeks from the last dose of systemic therapy before

radiotherapy,

- Median life expectancy of >3 months,

- Age > 18 years at the time of study entry,

- Adequate bone marrow function: Haemoglobin ≥ 9.0 g/dL, absolute neutrophil count (ANC)

≥ 1.5 x 109/L (> 1500 per mm3), platelet count ≥ 100 x 109/L (>100,000 per mm3),

- Female subjects 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 must have a negative serum pregnancy test upon study entry,

- Subject is willing and able to comply with the protocol for the duration of the study

including undergoing treatment and scheduled visits and examinations including

follow-up.

Exclusion Criteria:

- Patients without metastatic cancer (regional metastatic lymph nodes considered as

metastatic),

- Patients without bulky lesions,

- Median life expectancy of less than three months,

- Patients with prior radiation therapy to the same site,

- Contraindication to IV iodine contrast medium administration, particularly estimated

glomerular filtration rate (GFR) less than 45 mL/min/1.73 m2,

- History of autoimmune disease,

- Current or prior use of immunosuppressive medication within 28 days before enrollment

with the exception 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,

- History of primary immunodeficiency,

- History of allogeneic organ transplant,

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active

infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable

angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active

bleeding diatheses including any subject 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 subject to give written informed consent,

- Known history of previous clinical diagnosis of tuberculosis,

- History of leptomeningeal carcinomatosis,

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

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

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

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

- Subjects with uncontrolled seizures.

Studien-Rationale

Primary outcome:

1. Bystander and abscopal effects (Time Frame - 6 months):
Rates of significant (30% or more) tumor regression at the level of both the partially treated bulky tumors (bystander effects) and unirradiated oligometastases and/or regional lymph nodes (abscopal effect).



Secondary outcome:

1. Overall survival (Time Frame - Up to 100 weeks):
The length of time from the start of treatment for a cancer, that patients diagnosed with the disease are still alive.

2. Progression-free survival (Time Frame - Up to 100 weeks):
The length of time during and after the treatment of a cancer, that a patient lives without disease-progression.

3. Patient-reported outcome (PRO) (Time Frame - 3 months):
Health outcome directly reported by the patient who experienced the cancer-related symptoms.

4. Common Terminology Criteria for Adverse Events (CTCAE) v5.0 (Time Frame - Up to 100 weeks):
Clinician reported radiation related toxicity as a standardized system to quantify or grade the severity of adverse events that occur during or after radiation treatment.

5. Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (Time Frame - Up to 6 months):
The assessments of tumor response to radiotherapy will be performed using RECIST v1.1. criteria at 1 and 2 months post-treatment, and every 3 months thereafter using CT, MRI or PET-CT to assess the neoadjuvant potential of SBRT-PATHY expressed as significant (>30% tumor-volume reduction in respect to initial tumor volume) downsizing of unresectable bulky tumors into resectable tumors.

6. Timing (Time Frame - 6 months):
Determination of the optimal timing for radiotherapy treatment to be administered by correlating the clinical outcomes with the phase or position on the immune cycle at which the treatment occurred.

Studien-Arme

  • Active Comparator: Less favorable time-position in immune cycle
    Starting two weeks prior to the initiation of radiotherapy serial, 7x blood samples will be taken every two days, excluding the weekend (for example, if starting on a Monday: Monday-Wednesday-Friday-Monday-Wednesday-Friday and Monday), but also on the day of the first radiotherapy treatment, to define the serial high-sensitivity C-reactive protein (hs-CRP) test, LDH and white cell differential count (leucocytes: neutrophils, basophils, eosinophils, lymphocytes, monocytes). Data from the assays will be assembled in a spreadsheet and analyzed for levels and cyclical fluctuations to determine each patient's idiosyncratic immune cycle's periodicity and then each patient's time-position of initiation of treatment and response to therapy. SBRT-PATHY will be administered to this arm at an estimated "less favorable time-Position in immune cycle".
  • Experimental: Most favorable time-position in immune cycle
    Starting two weeks prior to the initiation of radiotherapy serial, 7x blood samples will be taken every two days, excluding the weekend (for example, if starting on a Monday: Monday-Wednesday-Friday-Monday-Wednesday-Friday and Monday), but also on the day of the first radiotherapy treatment, to define the serial high-sensitivity C-reactive protein (hs-CRP) test, LDH and white cell differential count (leucocytes: neutrophils, basophils, eosinophils, lymphocytes, monocytes). Data from the assays will be assembled in a spreadsheet and analyzed for levels and cyclical fluctuations to determine each patient's idiosyncratic immune cycle's periodicity and then each patient's time-position of initiation of treatment and response to therapy. SBRT-PATHY will be administered to this arm at an estimated "most favorable time-position in immune cycle".

Geprüfte Regime

  • SBRT-PATHY (SBRT-based PArtial Tumor irradiation targeting HYpoxic segment):
    Novel stereotactic high-dose partial irradiation of the hypoxic segment of bulky tumors.

Quelle: ClinicalTrials.gov


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