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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03377491




Registration number
NCT03377491
Ethics application status
Date submitted
6/12/2017
Date registered
19/12/2017
Date last updated
10/04/2023

Titles & IDs
Public title
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)
Scientific title
Pivotal, Randomized, Open-label Study of Tumor Treating Fields (TTFields, 150kHz) Concomitant With Gemcitabine and Nab-paclitaxel for Front-line Treatment of Locally-advanced Pancreatic Adenocarcinoma
Secondary ID [1] 0 0
EF-27
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pancreas Adenocarcinoma 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Devices - NovoTTF-200T
Treatment: Drugs - Gemcitabine
Treatment: Drugs - nab paclitaxel

Experimental: NovoTTF-200T - Patients receive TTFields using the NovoTTF-200T System together with gemcitabine and nab-Paclitaxel

Active Comparator: Best Standard of Care - Patients receive best standard of care with gemcitabine and nab-Paclitaxel


Treatment: Devices: NovoTTF-200T
Patients receive continuous TTFields treatment using the NovoTTF-200T 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.

Treatment: Drugs: 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.

Treatment: Drugs: 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.
Intervention code [1] 0 0
Treatment: Devices
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall survival
Timepoint [1] 0 0
4 years
Secondary outcome [1] 0 0
Progression-free survival
Timepoint [1] 0 0
4 years
Secondary outcome [2] 0 0
Local progression-free survival
Timepoint [2] 0 0
4 years
Secondary outcome [3] 0 0
Objective response rate
Timepoint [3] 0 0
4 years
Secondary outcome [4] 0 0
One-year survival rate
Timepoint [4] 0 0
4 years
Secondary outcome [5] 0 0
Quality of life
Timepoint [5] 0 0
4 years
Secondary outcome [6] 0 0
Pain-free survival
Timepoint [6] 0 0
4 years
Secondary outcome [7] 0 0
Puncture-free survival
Timepoint [7] 0 0
4 years
Secondary outcome [8] 0 0
Resectability rate
Timepoint [8] 0 0
4 years
Secondary outcome [9] 0 0
Toxicity profile
Timepoint [9] 0 0
4 years

Eligibility
Key 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-200T System independently or with the help of a caregiver

8. Signed informed consent form for the study protocol
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
10/02/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/10/2024
Actual
Sample size
Target
556
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,WA
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Greenslopes Private Hospital - Greenslopes
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St. John of God Murdoch Hospital - Murdoch
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Monash Medical Centre - Clayton
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Sydney Adventist Hospital - Wahroonga
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Westmead Hosptial - Westmead
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4120 - Greenslopes
Recruitment postcode(s) [2] 0 0
6150 - Murdoch
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VIC 3168 - Clayton
Recruitment postcode(s) [4] 0 0
NSW 2076 - Wahroonga
Recruitment postcode(s) [5] 0 0
NSW 2145 - Westmead
Recruitment outside Australia
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Puebla
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Toluca de Lerdo
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Toluca De Lerdo
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Veracruz
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Poznan
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
NovoCure Ltd.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Brief Summary:

The study is a prospective, randomized controlled phase III trial aimed to test the efficacy
and safety of Tumor Treating Fields (TTFields) in combination with gemcitabine and
nab-paclitaxel, for front line treatment of locally-advanced pancreatic adenocarcinoma.The
device is an experimental, portable, battery operated device for chronic administration of
alternating electric fields (termed TTFields or TTF) to the region of the malignant tumor, by
means of surface, insulated electrode arrays.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03377491
Trial related presentations / publications
Kirson ED, Gurvich Z, Schneiderman R, Dekel E, Itzhaki A, Wasserman Y, Schatzberger R, Palti Y. Disruption of cancer cell replication by alternating electric fields. Cancer Res. 2004 May 1;64(9):3288-95. doi: 10.1158/0008-5472.can-04-0083.
Kirson ED, Dbaly V, Tovarys F, Vymazal J, Soustiel JF, Itzhaki A, Mordechovich D, Steinberg-Shapira S, Gurvich Z, Schneiderman R, Wasserman Y, Salzberg M, Ryffel B, Goldsher D, Dekel E, Palti Y. Alternating electric fields arrest cell proliferation in animal tumor models and human brain tumors. Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10152-7. doi: 10.1073/pnas.0702916104. Epub 2007 Jun 5.
Stupp R, Wong ET, Kanner AA, Steinberg D, Engelhard H, Heidecke V, Kirson ED, Taillibert S, Liebermann F, Dbaly V, Ram Z, Villano JL, Rainov N, Weinberg U, Schiff D, Kunschner L, Raizer J, Honnorat J, Sloan A, Malkin M, Landolfi JC, Payer F, Mehdorn M, Weil RJ, Pannullo SC, Westphal M, Smrcka M, Chin L, Kostron H, Hofer S, Bruce J, Cosgrove R, Paleologous N, Palti Y, Gutin PH. NovoTTF-100A versus physician's choice chemotherapy in recurrent glioblastoma: a randomised phase III trial of a novel treatment modality. Eur J Cancer. 2012 Sep;48(14):2192-202. doi: 10.1016/j.ejca.2012.04.011. Epub 2012 May 18.
Kirson ED, Giladi M, Gurvich Z, Itzhaki A, Mordechovich D, Schneiderman RS, Wasserman Y, Ryffel B, Goldsher D, Palti Y. Alternating electric fields (TTFields) inhibit metastatic spread of solid tumors to the lungs. Clin Exp Metastasis. 2009;26(7):633-40. doi: 10.1007/s10585-009-9262-y. Epub 2009 Apr 23.
Giladi M, Schneiderman RS, Voloshin T, Porat Y, Munster M, Blat R, Sherbo S, Bomzon Z, Urman N, Itzhaki A, Cahal S, Shteingauz A, Chaudhry A, Kirson ED, Weinberg U, Palti Y. Mitotic Spindle Disruption by Alternating Electric Fields Leads to Improper Chromosome Segregation and Mitotic Catastrophe in Cancer Cells. Sci Rep. 2015 Dec 11;5:18046. doi: 10.1038/srep18046.
Stupp R, Taillibert S, Kanner AA, Kesari S, Steinberg DM, Toms SA, Taylor LP, Lieberman F, Silvani A, Fink KL, Barnett GH, Zhu JJ, Henson JW, Engelhard HH, Chen TC, Tran DD, Sroubek J, Tran ND, Hottinger AF, Landolfi J, Desai R, Caroli M, Kew Y, Honnorat J, Idbaih A, Kirson ED, Weinberg U, Palti Y, Hegi ME, Ram Z. Maintenance Therapy With Tumor-Treating Fields Plus Temozolomide vs Temozolomide Alone for Glioblastoma: A Randomized Clinical Trial. JAMA. 2015 Dec 15;314(23):2535-43. doi: 10.1001/jama.2015.16669.
Giladi M, Schneiderman RS, Porat Y, Munster M, Itzhaki A, Mordechovich D, Cahal S, Kirson ED, Weinberg U, Palti Y. Mitotic disruption and reduced clonogenicity of pancreatic cancer cells in vitro and in vivo by tumor treating fields. Pancreatology. 2014 Jan-Feb;14(1):54-63. doi: 10.1016/j.pan.2013.11.009. Epub 2013 Dec 4.
Stupp R, Taillibert S, Kanner A, Read W, Steinberg D, Lhermitte B, Toms S, Idbaih A, Ahluwalia MS, Fink K, Di Meco F, Lieberman F, Zhu JJ, Stragliotto G, Tran D, Brem S, Hottinger A, Kirson ED, Lavy-Shahaf G, Weinberg U, Kim CY, Paek SH, Nicholas G, Bruna J, Hirte H, Weller M, Palti Y, Hegi ME, Ram Z. Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial. JAMA. 2017 Dec 19;318(23):2306-2316. doi: 10.1001/jama.2017.18718. Erratum In: JAMA. 2018 May 1;319(17):1824.
Public notes

Contacts
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Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03377491