Dienstag, 11. Mai 2021
Navigation öffnen
Anzeige:
Vectibix
JOURNAL ONKOLOGIE – STUDIE

Efficacy and Safety of Dronabinol in the Improvement of Chemotherapy-induced and Tumor-related Symptoms in Advanced Pancreatic Cancer

Rekrutierend

NCT-Nummer:
NCT03984214

Studienbeginn:
Dezember 2019

Letztes Update:
20.11.2020

Wirkstoff:
Dronabinol in Oral Dosage Form, Placebo in Oral Dosage Form

Indikation (Clinical Trials):
Pancreatic Neoplasms, Nausea, Vomiting

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 3

Sponsor:
Arbeitsgemeinschaft medikamentoese Tumortherapie

Collaborator:
Medical University of Graz, Unidata Geodesign, Bionorica SE,

Studienleiter

Felix Keil, Prof.MD
Principal Investigator
Med. Dept. III, Hematolog and Oncology

Kontakt

Daniela Wolkersdorfer, PhD
Kontakt:
Phone: +43 662640
Phone (ext.): 4412
E-Mail: d.wolkersdorfer@agmt.at
» Kontaktdaten anzeigen

Studienlocations
(3 von 8)

Klinikum Wels-Grieskirchen GmbH, Abteilung für Innere Medizin IV
4600 Wels
AustriaRekrutierend» Google-Maps
Ansprechpartner:
Gudrun Piringer, MD
Phone: +43 7242 415
Phone (ext.): 3452
E-Mail: Gurdrun.Piringer@klinikum-wegr.at

Mathaeus Muehlberger, BScN
Phone: +43 7242 415
Phone (ext.): 3452
E-Mail: Mathaeus.Muehlberger@klinikum-wegr.at
» Ansprechpartner anzeigen
KABEG-Klinikum Klagenfurt am Woerthersee, Abteilung f. Anaesthesie u. Intensivmedizin
9020 Klagenfurt
AustriaRekrutierend» Google-Maps
Ansprechpartner:
Rudolf Likar, Prof.MD.MSc
Phone: +43 463 538
Phone (ext.): 26100
E-Mail: rudolf.likar@kabeg.at

Brigitte Trummer
Phone: +43 463 538
Phone (ext.): 35756
E-Mail: brigitte.trummer@kabeg.at
» Ansprechpartner anzeigen
LKH Hochsteiermark - Leoben, Abt. f. Innere Medizin, Haemato-Onkologie
8700 Leoben
AustriaRekrutierend» Google-Maps
Ansprechpartner:
Christoph Tinchon, MD, Lead
Phone: +43 3842 401
Phone (ext.): 2821
E-Mail: christoph.tinchon@kages.at

Manuela Maderdonner, BSc.,MSc.
Phone: +43 3842 401
Phone (ext.): 3402
E-Mail: manuela.maderdonner@kages.at
» Ansprechpartner anzeigen
IIIrd Medical Department, Private Medical University Hospital Salzburg
5020 Salzburg
AustriaRekrutierend» Google-Maps
Ansprechpartner:
Richard Greil, Prof.MD
Phone: +43 57255
Phone (ext.): 25801
E-Mail: r.greil@salk.at

Michaela Schachner, Mag.
Phone: +43 57255
Phone (ext.): 25823
E-Mail: m.schachner@salk.at
» Ansprechpartner anzeigen
Krankenhaus d. Barmherzigen Brüder, Abt. f. Innere Medizin
9300 St. Veit an der Glan
AustriaRekrutierend» Google-Maps
Ansprechpartner:
Harald Weiß, Senior MD
Phone: +43 4212 499
E-Mail: harald.weiss@bbstveit.at

Maria Piribauer, MD
Phone: +43 4212 499
E-Mail: maria.piribauer@bbstveit.at
» Ansprechpartner anzeigen
Pyhrn-Eisenwurzen Klinikum Steyr, Interne Medizin II
A-4400 Steyr
AustriaRekrutierend» Google-Maps
Ansprechpartner:
Georg Schreil, MD
Phone: +43 50554 66
Phone (ext.): 24208
E-Mail: georg.schreil@ooeg.at

Regina Neuhauser
Phone: +43 50554 66
Phone (ext.): 24202
E-Mail: regina.neuhauser@ooeg.at
» Ansprechpartner anzeigen
Medizinische Univ. Wien, Univ.Klinik f. Innere Medizin I, Onkologie
1090 Vienna
AustriaNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Gerald Prager, Ass.Prof.MD
Phone: +43 1 40400
Phone (ext.): 44450
E-Mail: gerald.prager@meduniwien.ac.at

Susanne Schlagbauer
E-Mail: susanne.schlagbauer@meduniwien.ac.at
» Ansprechpartner anzeigen
Hanusch Krankenhaus der Wiener Gebietskrankenkasse
1140 Vienna
AustriaRekrutierend» Google-Maps
Ansprechpartner:
Thamer Sliwa, MD
Phone: +43 1 910 21
Phone (ext.): 57301
E-Mail: thamer.sliwa@oegk.at

Anna Schipany, MSc
Phone: +43 1 910 21
Phone (ext.): 86907
E-Mail: anna.schipany@oegk.at
» Ansprechpartner anzeigen
Alle anzeigen

Studien-Informationen

Detailed Description:

Patients with pancreatic cancer suffer from multiple symptoms related to the tumor itself or

induced by the chemotherapy. The available supportive therapy is still not able to relief all

symptoms that are caused by the malignancy itself as well as by the antineoplastic therapy.

Additionally, anorexia and weight loss, that often result in increased morbidity and

mortality in this patient population as well as in psycho-social burden and suffering in

patients and their relatives, are unmet needs in pancreatic cancer patients.

Therapeutic approaches focus on treating the malignancy itself, additional nutritional

support and physical examination might prevent patients from further side effects such as

sarcopenia.

During the last decades a number of appetite-modulating drugs have been under clinical

investigation. A number of studies focused on the endocannabinoid system, which is involved

amongst others in appetite-modulating, antiemetic, analgesic and anti-inflammatory processes.

As dronabinol is already used as magistral formulation, its beneficial effect has often been

observed in these patients in the clinical routine, especially in patients with

therapy-refractory nausea and emesis. Due to its broad efficacy it might be of benefit for

patients suffering from malignancy. Thus, investigators want to evaluate the efficacy of

dronabinol in the improvement of chemotherapy-induced and tumor-related symptoms in advanced

pancreatic patients during systemic first-line chemotherapy. However, data on optimal dosage

are conflicting yet.

In detail, investigators want to study whether dronabinol has a positive influence on quality

of life and whether symptoms caused by the tumor or by the chemotherapy itself might be

palliated by dronabinol. Beneficial and potential harmful side effects and the personal

perception of advanced pancreatic cancer patients will be documented.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Male and female subjects aged ≥18

- Patients with diagnosis of locally advanced, inoperable or metastatic pancreatic

cancer, eligible for first-line chemotherapy with FOLFIRINOX or gemcitabine+Abraxane®

- According to investigator life expectancy of > 4 months at screening

- Female patients must either be post-menopausal or surgically sterilized or use a

highly effective method of birth control (hormonal contraceptives, intra-uterine

devices, or diaphragms with spermicide) for the duration of the study and/or must have

a negative pregnancy test (female patients with childbearing potential only)

- Willing and able to provide written informed consent.

- Written informed consent given prior to any trial-related procedure not part of the

normal medical practice.

Exclusion Criteria:

- Patients who are members of the staff of the trial center, staff of the sponsor or

CRO, the investigator him/herself or close relatives of the investigator.

- Simultaneous participation in another interventional clinical trial, participation in

another trial with less than 30 days or five half-lives of the IMP (whatever is

longer) to screening, or previous participation in this trial.

- Ineligible for chemotherapy treatment with FOLFIRINOX or gemcitabine+Abraxane®

- Use of dronabinol or cannabis-based medicine with THC as constituent within 6 months

before screening. A urine drug test will be performed during screening phase.

- Use of marihuana within the last 4 weeks and unwillingness to abstain for the duration

of the study. A urine drug test will be performed during screening phase.

- Currently receiving chemotherapy or anticipated use of chemotherapy due to any

condition not related to locally advanced or metastatic pancreatic cancer

- History of or existing cardiac diseases or pathological findings (e.g. chronic

insufficiency NYHA III/IV, severe arrhythmia, unstable angina pectoris, myocardial

infarction within the past 6 months, significant QT-prolongation etc.), which in the

opinion of the investigator might interfere with the safety or tolerability of the

study treatment. An ECG has to be done to exclude pathological findings and must not

be older than 3 months before screening or if none is available, has to be performed

during the screening phase and assessed prior to randomization

- Clinically relevant, severe pulmonary diseases, uncontrolled hypertension, or poorly

controlled diabetes

- History of or existing relevant CNS and/or psychiatric disorders (e.g. schizophrenia,

psychosis, manic and/or depressive disorders, suicidal ideations, etc) which might

interfere with the safety or tolerability of the study treatment. Patients with

reactive depression are not excluded from participation.

- Known current or past (within the last year prior to screening) alcohol, narcotics or

drug abuse

- Pregnancy or breast feeding

- Known allergy to cannabinoids and other constituents of the investigational medicinal

product

- Intake of prohibited concomitant medication

- Any other substantial medical condition that in the opinion of the investigator could

create undue risk to the subject or could affect adherence with the trial protocol

- Legal incapacity, limited legal capacity or any other condition which makes the

subject unable to understand the subject information and informed consent form (ICF)

- Patients unable or unwilling to waive driving motor vehicles or using machines

especially during titration period

- Unable or unwilling to comply with the protocol regulations

Studien-Rationale

Primary outcome:

1. Standardized area under the curve of the European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ)-C30 symptom summary score over the on-treatment period. (Time Frame - Prior to treatment start until end of 16 weeks maintenance treatment):
The EORTC-QLQ-C30 is an integrated system for assessing the health-related quality of life (QoL) of cancer patients participating in international clinical trials. The validated QLQ-C30 summary score is calculated as mean score of the 13 of the 15 EORTC QLQ-C30 scales (v3.0), based on 27 of 30 items (the Financial Impact scale and Quality of Life score are not included). A high score for a symptom scale / item (fatigue, nausea and vomiting, pain, dyspnoea, insomnia, appetite loss, constipation, diarrhoea) represents a high level of symptomatology / problems. A high score for a functional scale (physical functioning, role functioning, cognitive functioning, emotional functioning, social functioning) represents a high / healthy level of functioning. Scores for individual items: "Not at All" = 1 point, "A Little" = 2 points, "Quite a Bit" = 3 points, "Very Much" = 4 points. A linear transformation is used to standardize the raw score, so that overall scores range from 0 to 100.



Secondary outcome:

1. Standardized area under the curve of the European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ)-C30 symptom summary score over the maintenance period (Time Frame - After 4 weeks of treatment until week 16):
The European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ) is an integrated system for assessing the health-related quality of life (QoL) of cancer patients participating in international clinical trials. The validated QLQ-C30 summary score is calculated as mean score of items. A high score for a symptom scale / item (fatigue, nausea and vomiting, pain, dyspnoea, insomnia, appetite loss, constipation, diarrhoea) represents a high level of symptomatology / problems. Scores for individual items: "Not at All" = 1 point, "A Little" = 2 points, "Quite a Bit" = 3 points, "Very Much" = 4 points. A linear transformation is used to standardize the raw score, so that overall scores range from 0 to 100.

2. Change of European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ)-C30 symptom summary score from baseline to summary score over the maintenance period (Time Frame - From treatment start until week 16):
The European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ) is an integrated system for assessing the health-related quality of life (QoL) of cancer patients participating in international clinical trials. The validated QLQ-C30 summary score is calculated as mean score of items. A high score for a symptom scale / item (fatigue, nausea and vomiting, pain, dyspnoea, insomnia, appetite loss, constipation, diarrhoea) represents a high level of symptomatology / problems. Scores for individual items: "Not at All" = 1 point, "A Little" = 2 points, "Quite a Bit" = 3 points, "Very Much" = 4 points. A linear transformation is used to standardize the raw score, so that overall scores range from 0 to 100.

3. Symptom scales of European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ)-C30 (Time Frame - At baseline and 2-weekly until end of treatment at week 18):
A high score for a symptom scale / item (fatigue, nausea and vomiting, pain, dyspnoea, insomnia, appetite loss, constipation, diarrhoea) represents a high level of symptomatology / problems. Scores for individual items: "Not at All" = 1 point, "A Little" = 2 points, "Quite a Bit" = 3 points, "Very Much" = 4 points. A linear transformation is used to standardize the raw score, so that overall scores range from 0 to 100.

4. Global quality of life of the European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ)-C30 (Time Frame - At baseline and 2-weekly until end of treatment at week 18):
The European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ) is an integrated system for assessing the health-related quality of life (QoL) of cancer patients participating in international clinical trials. The validated QLQ-C30 summary score is calculated as mean score of items. A high score for the global health status (overall health during the past week) and global QoL (overall quality of life during the past week) represents a high QoL. Scores: 1 - 7, 1 = very poor and 7 = excellent. A linear transformation is used to standardize the raw score, so that overall scores range from 0 to 100.

5. Functional scales of the European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ)-C30 (Time Frame - At baseline and 2-weekly until end of treatment at week 18):
The European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ) is an integrated system for assessing the health-related quality of life (QoL) of cancer patients participating in international clinical trials. A high score for a functional scale (physical functioning, role functioning, cognitive functioning, emotional functioning, social functioning) represents a high / healthy level of functioning. Scores for individual items: "Not at All" = 1 point, "A Little" = 2 points, "Quite a Bit" = 3 points, "Very Much" = 4 points. A linear transformation is used to standardize the raw score, so that overall scores range from 0 to 100.

6. Mean change from baseline of the Glasgow Prognostic Score (Time Frame - At baseline and at end of treatment at week 16):
Change of serum levels of the score-defining biomarkers C-reactive protein (CRP) and albumin. Prognostic scores; 0 (CRP ≥ 10 mg/l), 1 (CRP > 10 mg/l and albumin ≥ 35 g/l), 2 CRP > 10 mg/l and albumin < 35g/l). Score 0 indicates good prognosis, score 1 intermediate prognosis and score 2 poor prognosis.

7. Amount of concomitant medication taken (Time Frame - From baseline until end of treatment at week 18):
Special focus on antiemetic, psychotropic and pain medication

8. Mean time to critical weight-loss (5%) (Time Frame - From baseline until end of treatment at week 16):
Assessed with a standard scale

9. Mean changes from baseline for Bioelectrical Impedance Analysis (BIA) parameter Lean body mass (LBM) (Time Frame - At baseline and at end of treatment at week 16):
Mean change of Lean body mass (LBM = Fat free mass FFM) kg

10. Mean changes from baseline for Bioelectrical Impedance Analysis (BIA) parameter Total body water (TBW) (Time Frame - At baseline and at end of treatment at week 16):
Mean change of Total body water (TBW) kg

11. Mean changes from baseline for Bioelectrical Impedance Analysis (BIA) parameter Fat mass (FM) (Time Frame - At baseline and at end of treatment at week 16):
Mean change of Fat mass (FM) kg

12. Mean changes from baseline for Bioelectrical Impedance Analysis (BIA) parameter Body cell mass (BCM) (Time Frame - At baseline and at end of treatment at week 16):
Mean change of Body cell mass (BCM) kg

13. Mean changes from baseline for Bioelectrical Impedance Analysis (BIA) parameter Extracellular mass (EM) (Time Frame - At baseline and at end of treatment at week 16):
Mean change of Extracellular mass (ECM) kg

14. Mean changes from baseline for Bioelectrical Impedance Analysis (BIA) parameter Phase angle (PA) (Time Frame - At baseline and at end of treatment at week 16):
Mean change of Phase angle (PA); Phase Angle has long been linked to nutritional status. This marker is fast becoming recognised as a global health marker in total body health assessment. A higher Phase Angle could mean an increase in muscle mass (body cell mass) or a decrease in fluid, either from recovery from infection or injury (a good thing!) or a decrease in fluid from dehydration (a bad thing!). A loss of fat could also increase Phase Angle. A lower Phase Angle could mean a loss of muscle mass (a bad thing), or an increase of fluid (rehydrating which is a good thing, or sign of inflammation or infection - a bad thing), or gaining fat (which could be a good or bad thing depending on your state of health). Phase Angle is a direct measurement, (not a calculation using equations) of the cell membrane.

15. Mean changes from baseline for Bioelectrical Impedance Analysis (BIA) parameter Resistance (Rz) (Time Frame - At baseline and at end of treatment at week 16):
Mean change of Resistance (Rz), unit ohm; the resistance reflects the water or fluid in the body

16. Mean changes from baseline for Bioelectrical Impedance Analysis (BIA) parameter Reactance(Xc) (Time Frame - At baseline and at end of treatment at week 16):
Mean change of Reactance (Xc), unit ohm; reactance reflects the body cell mass.

17. Mean change from baseline of muscle strength (Time Frame - At baseline and at end of treatment at week 16):
To assess physical strength of patient's handgrip strength will be measured prior and after study treatment using a hydraulic hand dynamometer; mean value of three consecutive measurements will be documented

18. Proportion of patients not adhering to individual baseline chemotherapy regimen (Time Frame - From baseline until end of treatment at week 18):
Percentage of patients who do not receive full dose of planned chemotherapy regimen and/or within scheduled time frame (interruption or delay)

19. Chemotherapeutic dose intensity over the treatment period of 18 weeks (Time Frame - From baseline until end of treatment at week 18):
The total amount of applied chemotherapy over the study treatment phase is documented

20. Frequency and severity of (serious) adverse events (S)AE (Time Frame - From baseline until safety visit at week 22):
Assessed with Common Terminology Criteria for Adverse Events (NCI-CTCAE V5.0)

21. Incidence of adverse drug reactions (ARs) (Time Frame - From baseline until safety visit at week 22):
Frequency and severity of ARs

22. Progression-free survival (PFS) (Time Frame - From treatment start until the date of first documented progression or death from any cause assessed up to week 22):
PFS in months; ; patients will be asked to agree on collection of data regarding PFS also after end of trial

23. Overall survival (OS) (Time Frame - From treatment start until death from any cause assessed up to week 22):
OS in months; ; patients will be asked to agree on collection of data regarding PFS also after end of trial

Studien-Arme

  • Active Comparator: Dronabinol
    BX-1 contains 25 mg dronabinol/ml (2.5% delta-9-trans-tetrahydrocannabinol = THC), oral solution; three applications per day from 2.5 mg (3 x 1 droplet) up to 30 mg (3 x 12 droplets)
  • Placebo Comparator: Placebo
    Placebo: oral solution with cannabis flavor without active substance and otherwise identical to active comparator, three applications per day from 3 x 1 droplet up to 3 x 12 droplets

Geprüfte Regime

  • Dronabinol in Oral Dosage Form (BX-1):
    Titration period for 4 weeks: titration according to tolerability from 2.5 mg (3 x 1 droplet) up to 30 mg (3 x 12 droplets) per day; dose increased by 2.5 mg (3 x 1 droplet) every other day Maintenance period for 12 weeks: individually tolerated maximum dose (up to 30 mg ≙ 3 x 12 droplets) at end of titration period will be continued for maintenance treatment Tapering period for 2 weeks: dose is decreased every other day by 5 mg (3 x 2 droplets) Safety follow-up: 4 weeks after end of treatment
  • Placebo in Oral Dosage Form:
    Titration period for 4 weeks: titration according to tolerability from 3 x 1 droplet up to 3 x 12 droplets per day; dose increased by 3 x 1 droplet every other day Maintenance period for 12 weeks: individually tolerated maximum dose (up to 3 x 12 droplets) at end of titration period will be continued for maintenance treatment Tapering period for 2 weeks: dose is decreased every other day by 3 x 2 droplets Safety follow-up: 4 weeks after end of treatment

Quelle: ClinicalTrials.gov


Das könnte Sie auch interessieren
Was Krebspatienten in der kalten Jahreszeit beachten sollten
Was+Krebspatienten+in+der+kalten+Jahreszeit+beachten+sollten
© Rido - stock.adobe.com

Außen kalt, innen überheizt, dazu Glatteis, Schnee und trübes Licht – der Winter ist für Krebspatienten keine leichte Zeit. Aufgrund der geschwächten Immunabwehr und den damit einhergehenden gesundheitlichen Beeinträchtigungen sind besondere Vorsichtsmaßnahmen zu beachten. Im Monatsthema Dezember gibt das ONKO-Internetportal hilfreiche Tipps, wie Krebspatienten gut und sicher durch die kalten Monate kommen.

Wirksamkeitsstudie wird mit 1,5 Millionen Euro gefördert
Wirksamkeitsstudie+wird+mit+1%2C5+Millionen+Euro+gef%C3%B6rdert
©Photographee.eu - stock.adobe.com

Ein Forschungsteam der Medizinischen Fakultät der Universität Duisburg-Essen (UDE) untersucht in einer Studie, wie effektiv Menschen mit einer Krebserkrankung durch das Online-Tool Make It (1)  geholfen werden kann. Das Bundesministerium für Bildung und Forschung (BMBF) unterstützt die Arbeit des Teams der Klinik für Psychosomatische Medizin und Psychotherapie am LVR-Klinikum Essen mit rund 1,5 Millionen Euro bis...