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JOURNAL ONKOLOGIE – STUDIE

Effect of Tumor Treating Fields (TTFields, 150 kHz) as Front-Line Treatment of Locally-advanced Pancreatic Adenocarcinoma Concomitant With Gemcitabine and Nab-paclitaxel (PANOVA-3)

Rekrutierend

NCT-Nummer:
NCT03377491

Studienbeginn:
Mai 2018

Letztes Update:
11.03.2021

Wirkstoff:
nab paclitaxel, Gemcitabine

Indikation (Clinical Trials):
Adenocarcinoma

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 3

Sponsor:
NovoCure Ltd.

Collaborator:
-

Kontakt

Studienlocations
(3 von 96)

Banner MD Anderson Cancer Center
85234 Gilbert
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Charlotte Tsinnijinnie
Phone: 480-256-5164
E-Mail: charlotte.tsinnijinnie@bannerhealth.com
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Arizona Oncology Associates, PC- HOPE - US Oncology Research
85711 Tucson
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Donna Capps, MA
Phone: 281-863-6662
E-Mail: donna.capps@mckesson.com
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Dignity Health - Mercy Cancer Centers
95816 Sacramento
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Dawn Diorio, RN BSN BA CCRP
Phone: (916) 863-8731
E-Mail: dawn.diorio@dignityhealth.org
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Boca Raton Regional Hospital, Lynn Cancer Institute
33486 Boca Raton
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Ileana Vargas
Phone: 561-955-3481
E-Mail: ivargas@baptisthealth.net
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Florida Cancer Specialists
33705 Saint Petersburg
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Rebecca "Dawn" McCrery
Phone: 727-216-1143
Phone (ext.): 1-3085
E-Mail: rmccrery@flcancer.com
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Illinois Cancer Specialist - US Oncology Research
60005 Arlington Heights
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Donna Capps, MA
Phone: 281-863-6662
E-Mail: donna.capps@mckesson.com
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Loyola University Medical Center
60153 Maywood
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Beth Chiappetta, RN, BSN, CCRP
Phone: 708-216-2568
E-Mail: BCHIAPPETTA@lumc.edu


Phone: 708-216-4498
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Norton Cancer Institute, Norton Healthcare Pavilion
40202 Louisville
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Kasaundra Thomas
Phone: 502-629-3449
E-Mail: Kasaundra.Thomas@nortonhealthcare.org
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Maryland Oncology Hematology, P.A - US Oncology Research
21044 Columbia
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Donna Capps, MD
Phone: 281-863-6662
E-Mail: donna.capps@mckesson.com
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Cancer and Hematology Centers of Western Michigan, PC
49503 Grand Rapids
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Ansprechpartner:
Penny Berger
Phone: 616-954-5550
Phone (ext.): 2041
E-Mail: pberger@chcwm.com
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University of Oklahoma Health Sciences Center
73104 Oklahoma City
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Ansprechpartner:
Clinical Trials Office
Phone: 405-271-8777
E-Mail: scc-clinical-trials-office@ouhsc.edu
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Willamette Valley Cancer Institute and Research Center - US Oncology Research
97401 Eugene
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Donna Capps, MA
Phone: 281-863-6662
E-Mail: donna.capps@mckesson.com
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Texas Oncology - Beaumont Mamie McFaddin Ward Cancer Center - US Oncology Research
77702 Beaumont
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Donna Capps, MA
Phone: 281-863-6662
E-Mail: donna.capps@mckesson.com
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Texas Oncology - El Paso Cancer Treatment Center Gateway - US Oncology Research
79915 El Paso
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Donna Capps, MA
Phone: 281-863-6662
E-Mail: donna.capps@mckesson.com
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Oncology and Hematology Associates of Southwest Virginia, Inc., DBA Blue Ridge Cancer Care - US Oncology Research
24014 Roanoke
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Donna Capps, MA
Phone: 281-863-6662
E-Mail: donna.capps@mckesson.com
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Univ. Klinik für Innere Medizin III der PMU
5020 Salzburg
AustriaRekrutierend» Google-Maps
Ansprechpartner:
Richard Greil, Prim. Univ.-Prof. Dr.
Phone: +43 (0)5 7255-25823
E-Mail: r.greil@salk.at
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Centre Hospitalier de I'Universitaire de de Montreal (CHUM)
H2X 3E4 Montréal
CanadaRekrutierend» Google-Maps
Ansprechpartner:
Lynda Dufresne
Phone: 514 890-8000 poste 35281
E-Mail: lynda.dufresne.chum@ssss.gouv.qc.ca
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Centre Hospitalier Universitaire de Sherbrooke CIUSSS de l'Estrie - CHUS
J1G 1B1 Sherbrooke
CanadaRekrutierend» Google-Maps
Ansprechpartner:
Michelle Roy
Phone: 819-346-1110 ext 12848
E-Mail: michelle.roy.ciussse-chus@ssss.gouv.qc.ca
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Hopital haut-Léveque CHU Bordeaux - Service d'Hépato- Gastroentérologie et d'Oncologie digestive
33604 Pessac
FranceRekrutierend» Google-Maps
Ansprechpartner:
Jean-Frédéric Blanc, Pr.
E-Mail: jean-frederic.blanc@chu-bordeaux.fr
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Institut de Cancérologie de l'Ouest
49055 Angers cedex
FranceRekrutierend» Google-Maps
Ansprechpartner:
Hélène Sénellart, MD
Phone: +33 2 40 67 99 48
E-Mail: Helene.Senellart@ico.unicancer.fr
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A.O. SS Antonio e Biagio e Cesare Arrigo
15121 Alessandria
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Ansprechpartner:
Giovanna Paola Bellotti, Dr.
Phone: + 39 0131 206753
E-Mail: gbellotti@ospedale.al.it
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Oncology Clinic Clinical Hospital of Przemienienia Pańskiego UM in Poznaniu
60-596 Poznań
PolandRekrutierend» Google-Maps
Ansprechpartner:
Rodryg Ramlau, Prof.
Phone: +48 61 854 90 40
E-Mail: rramlau@gmail.com
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Alle anzeigen

Studien-Informationen

Detailed Description:

PAST PRE-CLINICAL AND CLINICAL EXPERIENCE:

The effect of the electric fields (TTFields, TTF) has demonstrated significant activity in in

vitro and in vivo pancreatic adenocarcinoma pre-clinical models both as a single modality

treatment and in combination with chemotherapies. TTFields have been demonstrated to act

synergistically with taxanes and have been shown to be additive when combined with other

chemotherapies including gemcitabine. In addition, TTFields have shown to inhibit metastatic

spread of malignant melanoma in in vivo experiment.

In a pilot study, 40 patients with locally advanced or metastatic pancreatic adenocarcinoma

received gemcitabine together with TTFields (150 kHz) or gemcitabine and nab-paclitaxel

together with TTFields (150 kHz) applied to the abdomen until disease progression. The

combination was well tolerated and the only device-related adverse event was contact

dermatitis.

In addition, a phase III trial of Optune® (200 kHz) as monotherapy compared to active

chemotherapy in recurrent glioblastoma patients showed TTFields to be equivalent to active

chemotherapy in extending survival, associated with minimal toxicity, good quality of life,

and activity within the brain (14% response rate) (Stupp R., et al., EJC 2012). Finally, a

phase III trial of Optune® combined with maintenance temozolomide compared to maintenance

temozolomide alone has shown that combined therapy led to a significant improvement in both

progression free survival and overall survival in patients with newly diagnosed glioblastoma

without the addition of high grade toxicity and without decline in quality of life (Stupp R.,

et al., JAMA 2017).

DESCRIPTION OF THE TRIAL:

All patients included in this trial are patients with locally advanced pancreatic

adenocarcinoma. In addition, all patients must meet all eligibility criteria.

Eligible patients will be randomly assigned to one of two groups:

1. Patients receive gemcitabine and nab-paclitaxel in combination with TTFields using the

NovoTTF-100L(P) System.

2. Patients receive gemcitabine and nab-paclitaxel without TTFields.

Patients will be randomized at a 1:1 ratio. Baseline tests will be performed in patients

enrolled in both arms. If assigned to the NovoTTF-100L(P) group, the patients will be treated

continuously with the device until progression in the abdomen. On both arms, patients who

have progression outside the abdomen will switch to a second line treatment according to

local practice.

SCIENTIFIC BACKGROUND:

Electric fields exert forces on electric charges similar to the way a magnet exerts forces on

metallic particles within a magnetic field. These forces cause movement and rotation of

electrically charged biological building blocks, much like the alignment of metallic

particles seen along the lines of force radiating outwards from a magnet.

Electric fields can also cause muscles to twitch and if strong enough may heat tissues.

TTFields are alternating electric fields of low intensity. This means that they change their

direction repetitively many times a second. Since they change direction very rapidly (150

thousand times a second), they do not cause muscles to twitch, nor do they have any effects

on other electrically activated tissues in the body (brain, nerves and heart). Since the

intensities of TTFields in the body are very low, they do not cause heating.

The breakthrough finding made by Novocure was that finely tuned alternating fields of very

low intensity, now termed TTFields (Tumor Treating Fields), cause a significant slowing in

the growth of cancer cells. Due to the unique geometric shape of cancer cells when they are

multiplying, TTFields cause electrically-charged cellular components of these cells to change

their location within the dividing cell, disrupting their normal function and ultimately

leading to cell death. In addition, cancer cells also contain miniature building blocks which

act as tiny motors in moving essential parts of the cells from place to place. TTFields

interfere with the normal orientation of these tiny motors related to other cellular

components since they are electrically-charged as well. As a result of these two effects,

tumor cell division is slowed, results in cellular death or reverses after continuous

exposure to TTFields.

Other cells in the body (normal healthy tissues) are affected much less than cancer cells

since they multiply at a much slower rate if at all. In addition TTFields can be directed to

a certain part of the body, leaving sensitive areas out of their reach. Finally, the

frequency of TTFields applied to each type of cancer is specific and may not damage normally

dividing cells in healthy tissues.

In conclusion, TTFields hold the promise of serving as a brand new treatment for pancreatic

adenocarcinoma with very few side effects.

Ein-/Ausschlusskriterien

Inclusion Criteria:

1. 18 years of age and older

2. Life expectancy of ≥ 3 months

3. Histological/cytological diagnosis of de novo adenocarcinoma of the pancreas

4. Unresectable, locally advanced stage disease according to the following criteria:

- Head/uncinate process:

1. Solid tumor contact with SMA>180°

2. Solid tumor contact with the CA>180°

3. Solid tumor contact with the first jejunal SMA branch

4. Unreconstructible SMV/PV due to tumor involvement or occlusion (can be d/t

tumor or bland thrombus)

5. Contact with most proximal draining jejunal branch into SMV

- Body and tail

1. Solid tumor contact of >180° with the SMA or CA

2. Solid tumor contact with the CA and aortic involvement

3. Unreconstructible SMV/PV due to tumor involvement or occlusion (can be d/t

tumor or bland thrombus)

- No distant metastasis, including non-regional lymph node metastasis

- No borderline resectable (per Al-Hawary MM, et al., Radiology 201414)

5. ECOG score 0-2

6. Amenable and assigned by the investigator to receive therapy with gemcitabine and

nab-paclitaxel

7. Able to operate the NovoTTF-100L(P) System independently or with the help of a

caregiver

8. Signed informed consent form for the study protocol

Exclusion Criteria:

1. Prior palliative treatment (e.g. surgery, radiation) to the tumor

2. Cancer requiring anti-tumor treatment within the 5 years before inclusion, excluding

treated stage I prostate cancer, in situ cervical or uterus cancer, in situ breast

cancer and non-melanomatous skin cancer.

3. Serious co-morbidities:

1. Clinically significant (as determined by the investigator) hematological, hepatic

and renal dysfunction, defined as: Neutrophil count < 1.5 x 10^9/L and platelet

count < 100 x 10^9/L; bilirubin > 1.5 x Upper Limit of Normal (ULN); AST and/or

ALT > 2.5 x ULN; and serum creatinine > 1.5 x ULN.

2. History of significant cardiovascular disease unless the disease is well

controlled. Significant cardiac disease includes second/third degree heart block;

significant ischemic heart disease; poorly controlled hypertension; congestive

heart failure of the New York Heart Association (NYHA) Class II or worse (slight

limitation of physical activity; comfortable at rest, but ordinary activity

results in fatigue, palpitation or dyspnea).

3. History of arrhythmia that is symptomatic or requires treatment. Patients with

atrial fibrillation or flutter controlled by medication are not excluded from

participation in the trial.

4. History of cerebrovascular accident (CVA) within 6 months prior to randomization

or that is not stable.

5. Active infection or serious underlying medical condition that would impair the

ability of the patient to receive protocol therapy.

6. History of any psychiatric condition that might impair patient's ability to

understand or comply with the requirements of the study or to provide consent.

4. Concurrent anti-tumor therapy beyond gemcitabine and nab-paclitaxel

5. Implantable electronic medical devices in the torso, such as pacemakers

6. Known severe hypersensitivities to medical adhesives or hydrogel, or to one of the

chemotherapies used in this trial.

7. Pregnancy or breast-feeding (female patients with reproductive potential and their

partners must accept to use effective contraception throughout the entire study period

and for 3 months after the end of treatment). All patients who are capable of becoming

pregnant must take a pregnancy test which is negative within 72 hours before beginning

treatment. The definition of effective contraception is left up to the decision of the

investigator.

8. Unable to follow the protocol for medical, psychological, familial, geographic or

other reasons.

9. Admitted to an institution by administrative or court order.

Studien-Rationale

Primary outcome:

1. Overall survival (Time Frame - 4 years)



Secondary outcome:

1. Progression-free survival (Time Frame - 4 years)

2. Local progression-free survival (Time Frame - 4 years)

3. Objective response rate (Time Frame - 4 years)

4. One-year survival rate (Time Frame - 4 years)

5. Quality of life (Time Frame - 4 years):
Quality of life will be assessed using the EORTC QLQ C-30 questionnaire with EORTC QLQ-PAN26 (Pancreatic Cancer symptom) supplement.

6. Pain-free survival (Time Frame - 4 years):
Pain-free survival will measured as the duration between the time of randomization until a greater than or equal to two-point decline from a baseline measurement in a patient self-reported visual analogue scale (VAS) is recorded or death, whichever occurs first.

7. Puncture-free survival (Time Frame - 4 years)

8. Resectability rate (Time Frame - 4 years)

9. Toxicity profile (Time Frame - 4 years):
Toxicity profile in patients treated with TTFields in combination with gemcitabine and nab-paclitaxel compared to the toxicity profile of patients treated with chemotherapy alone, measured by the rate of treatment-emergent toxicities in both arms. Adverse events will be collected and recorded based on the revised Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

Studien-Arme

  • Experimental: NovoTTF-100L(P)
    Patients receive TTFields using the NovoTTF-100L(P) System together with gemcitabine and nab-Paclitaxel
  • Active Comparator: Best Standard of Care
    Patients receive best standard of care with gemcitabine and nab-Paclitaxel

Geprüfte Regime

  • NovoTTF-100L(P) (TTFields):
    Patients receive continuous TTFields treatment using the NovoTTF-100L(P) device. TTFields treatment will consist of wearing four electrically insulated electrode arrays on the torso. The treatment enables the patient to maintain regular daily routine.
  • Gemcitabine:
    Gemcitabine 1000 mg/m^2 over 30 minute infusion will be administered immediately after nab-paclitaxel on Days 1, 8 and 15 of each 28-day cycle.
  • nab paclitaxel:
    nab-paclitaxel 125 mg/m^2 administered as an intravenous infusion over 30-40 minutes on Days 1, 8 and 15 of each 28-day cycle.

Quelle: ClinicalTrials.gov


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