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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04935359




Registration number
NCT04935359
Ethics application status
Date submitted
21/06/2021
Date registered
23/06/2021
Date last updated
27/11/2024

Titles & IDs
Public title
Study of Efficacy and Safety of NIS793 in Combination With Standard of Care (SOC) Chemotherapy in First-line Metastatic Pancreatic Ductal Adenocarcinoma (mPDAC) - daNIS-2
Scientific title
A Randomized, Double-blind, Phase III Study, Comparing NIS793 in Combination With Gemcitabine and Nab-paclitaxel Versus (vs.) Placebo Combined With Gemcitabine and Nab-paclitaxel for First Line Treatment of Metastatic Pancreatic Ductal Adenocarcinoma (mPDAC) - daNIS-2
Secondary ID [1] 0 0
2021-000591-10
Secondary ID [2] 0 0
CNIS793B12301
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Pancreatic Ductal Adenocarcinoma 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - NIS793
Treatment: Drugs - Nab-paclitaxel
Treatment: Drugs - Gemcitabine
Treatment: Drugs - Placebo

Experimental: Safety run-in part: NIS793+gemcitabine+nab-paclitaxel - In the safety run-in part, participants will receive a combination of NIS793, gemcitabine and nab-paclitaxel.

Experimental: Randomized part: NIS793+gemcitabine+nab-paclitaxel - Participants will receive a combination of NIS793, gemcitabine and nab-paclitaxel

Note: As of 07-Jul-2023, treatment with NIS793/placebo was stopped.

Placebo comparator: Randomized part: placebo+gemcitabine+nab-paclitaxel - Participants will receive a combination of placebo, gemcitabine and nab-paclitaxel

Note: As of 07-Jul-2023, treatment with NIS793/placebo was stopped.


Treatment: Drugs: NIS793
Concentrate for solution infusion (Liquid in Vial)

Treatment: Drugs: Nab-paclitaxel
Per locally approved formulation

Treatment: Drugs: Gemcitabine
Per locally approved formulation

Treatment: Drugs: Placebo
Dextrose 5% in water (D5W) solution for infusion
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety run-in part: Percentage of participants with dose limiting toxicities (DLTs) during the first cycle (4 weeks) of treatment.
Timepoint [1] 0 0
Up to 4 weeks
Primary outcome [2] 0 0
Randomized part: Overall survival (OS)
Timepoint [2] 0 0
From randomization up to death, assessed up to approximately 19 months
Secondary outcome [1] 0 0
Percentage of participants with Adverse Events (AEs)
Timepoint [1] 0 0
Up to approximately 19 months
Secondary outcome [2] 0 0
Percentage of participants with dose interruptions and dose reductions of NIS793 in combination with gemcitabine and nab-paclitaxel
Timepoint [2] 0 0
Up to approximately 19 months
Secondary outcome [3] 0 0
Dose intensity of NIS793 in combination with gemcitabine and nab-paclitaxel
Timepoint [3] 0 0
Up to approximately 19 months
Secondary outcome [4] 0 0
Progression-free survival (PFS) by investigator assessment per RECIST 1.1
Timepoint [4] 0 0
From enrollment (run-in part) or randomization (randomized part) up to disease progression or death, assessed up to approximately 19 months
Secondary outcome [5] 0 0
Overall response rate (ORR) by investigator assessment per RECIST 1.1
Timepoint [5] 0 0
Up to approximately 19 months
Secondary outcome [6] 0 0
Disease control rate (DCR) by investigator assessment per RECIST 1.1
Timepoint [6] 0 0
Up to approximately 19 months
Secondary outcome [7] 0 0
Time to response (TTR) by investigator assessment per RECIST 1.1
Timepoint [7] 0 0
From enrollment (run-in part) or randomization (randomized part) up to first documented response, assessed up to approximately 19 months
Secondary outcome [8] 0 0
Safety run-in part: Overall Survival (OS)
Timepoint [8] 0 0
From enrollment up to death, assessed up to approximately 19 months
Secondary outcome [9] 0 0
Maximum concentration (Cmax) of NIS793 in combination with gemcitabine and nab-paclitaxel
Timepoint [9] 0 0
From date of first study drug intake up to approximately 19 months
Secondary outcome [10] 0 0
Trough Concentration (Ctrough) of NIS793 in combination with gemcitabine and nab-paclitaxel
Timepoint [10] 0 0
From date of first study drug intake up to approximately 19 months
Secondary outcome [11] 0 0
Area under the curve from time zero to the last measurable concentration sampling time (AUClast) of NIS793 in combination with gemcitabine and nab-paclitaxel
Timepoint [11] 0 0
From date of first study drug intake up to approximately 19 months
Secondary outcome [12] 0 0
Area under the curve calculated to the end of a dosing interval (tau) at steady-state (AUCtau) of NIS793 in combination with gemcitabine and nab-paclitaxel
Timepoint [12] 0 0
From date of first study drug intake up to approximately 19 months
Secondary outcome [13] 0 0
Time to reach maximum concentration (Tmax) of NIS793 in combination with gemcitabine and nab-paclitaxel
Timepoint [13] 0 0
From date of first study drug intake up to approximately 19 months
Secondary outcome [14] 0 0
Randomized part: NIS793 serum concentration
Timepoint [14] 0 0
From date of first study drug intake up to approximately 19 months
Secondary outcome [15] 0 0
Randomized part: Anti-drug antibodies (ADA) against NIS793 prevalence at baseline
Timepoint [15] 0 0
Baseline
Secondary outcome [16] 0 0
Randomized part: ADA (anti-NIS793) incidence on treatment
Timepoint [16] 0 0
From date of first study drug intake up to approximately 19 months

Eligibility
Key inclusion criteria
* Applicable for both Safety run-in and Randomized part

* Participants aged =18 years with histologically or cytologically confirmed (based on local assessment and per local guidelines) mPDAC eligible for treatment in the first line setting and not amenable for potentially curative surgery
* Presence of at least one measurable lesion assessed by Computerized Tomography (CT) and/or Magnetic Resonance Imaging (MRI) according to RECIST 1.1
* Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
* Adequate organ function (assessed by central laboratory for eligibility)
* Participants must have recovered from treatment-related toxicities of prior anticancer therapies to grade = 1 (CTCAE v 5.0) at time of screening, except alopecia.

Main
Minimum age
18 Years
Maximum age
100 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Applicable for both Safety run-in and Randomized part

* Previous systemic anti-cancer treatment for metastatic PDAC
* Pancreatic neuroendocrine (islet) or acinar tumors
* Participants with known status of microsatellite instability-high (MSI-H) or mismatch repair-deficient pancreatic cancer (if status is not already available, testing is not required at screening).
* Participant has not recovered from a major surgery performed prior to start of study treatment or has had a major surgery within 4 weeks prior to start of study treatment.
* Radiation therapy or brain radiotherapy = 4 weeks prior to start of study treatment (palliative radiotherapy to bone lesions allowed > 2 weeks prior to start of study treatment).
* Impaired cardiac function or clinically significant cardio-vascular disease
* Use of hematopoietic growth factors or transfusion support = 2 weeks prior to start of study treatment.
* Participant has conditions that are considered to have a high risk of clinically significant gastrointestinal tract bleeding or any other condition associated with or history of significant bleeding.
* Serious non-healing wounds.
* Pregnant or breast-feeding women
* Women of childbearing potential, unless willing to use highly effective contraception methods during treatment and after stopping study treatments as indicated
* Pre-existing peripheral neuropathy > grade 1 (CTCAE v5.0)

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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/09/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
13/08/2024
Sample size
Target
Accrual to date
Final
511
Recruitment in Australia
Recruitment state(s)
SA,WA
Recruitment hospital [1] 0 0
Novartis Investigative Site - Adelaide
Recruitment hospital [2] 0 0
Novartis Investigative Site - Perth
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
6009 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
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United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Indiana
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United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
Texas
Country [7] 0 0
United States of America
State/province [7] 0 0
Utah
Country [8] 0 0
United States of America
State/province [8] 0 0
Washington
Country [9] 0 0
Belgium
State/province [9] 0 0
Bonheiden
Country [10] 0 0
Belgium
State/province [10] 0 0
Bruxelles
Country [11] 0 0
Belgium
State/province [11] 0 0
Edegem
Country [12] 0 0
Belgium
State/province [12] 0 0
Leuven
Country [13] 0 0
Brazil
State/province [13] 0 0
Distrito Federal
Country [14] 0 0
Brazil
State/province [14] 0 0
Rio Grande Do Sul
Country [15] 0 0
Brazil
State/province [15] 0 0
RS
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Brazil
State/province [16] 0 0
SP
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Canada
State/province [17] 0 0
Ontario
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Quebec
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China
State/province [19] 0 0
Guangdong
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China
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Heilongjiang
Country [21] 0 0
China
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Jiangsu
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China
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Liaoning
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China
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Shandong
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China
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Shanxi
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China
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Sichuan
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China
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Zhejiang
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Beijing
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Shanghai
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China
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Tianjin
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Czechia
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Czech Republic
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Czechia
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CZE
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Czechia
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Praha 4
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Finland
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Helsinki
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Finland
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Tampere
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France
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Alpes Maritimes
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France
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Avignon
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France
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Besancon Cedex
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France
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Creteil
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France
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Lyon 08
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Marseille
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Montpellier
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Nantes Cedex 1
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France
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Paris
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Germany
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Berlin
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Germany
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Bochum
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Germany
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Essen
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Germany
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Frankfurt
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Germany
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Halle S
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Germany
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Hamburg
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Germany
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Ulm
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Greece
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Thessaloniki
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Hungary
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Budapest
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Debrecen
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Jerusalem
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Israel
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Ramat Gan
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Israel
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Tel Aviv
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Italy
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FI
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Italy
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MI
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Italy
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VR
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Japan
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Aichi
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Japan
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Chiba
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Kanagawa
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Japan
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Osaka
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Japan
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Tokyo
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Korea, Republic of
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Seocho Gu
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Korea, Republic of
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Seoul
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Netherlands
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Utrecht
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Norway
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Oslo
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Russian Federation
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Omsk
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Russian Federation
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Pushkin Saint Petersburg
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Singapore
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Singapore
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Slovakia
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Slovak Republic
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Slovakia
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Banska Bystrica
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Slovakia
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Kosice
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Spain
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Catalunya
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Galicia
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Spain
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Madrid
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Sweden
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Malmo
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Sweden
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Umea
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Switzerland
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Bellinzona
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Switzerland
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Geneve 14
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Switzerland
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St Gallen
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Taiwan
State/province [83] 0 0
Taipei
Country [84] 0 0
Taiwan
State/province [84] 0 0
Taoyuan
Country [85] 0 0
Turkey
State/province [85] 0 0
Adana
Country [86] 0 0
Turkey
State/province [86] 0 0
Ankara
Country [87] 0 0
Turkey
State/province [87] 0 0
Istanbul
Country [88] 0 0
Turkey
State/province [88] 0 0
Izmir
Country [89] 0 0
United Kingdom
State/province [89] 0 0
Surrey
Country [90] 0 0
United Kingdom
State/province [90] 0 0
Cambridge
Country [91] 0 0
United Kingdom
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Liverpool
Country [92] 0 0
United Kingdom
State/province [92] 0 0
London
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United Kingdom
State/province [93] 0 0
Oxford

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to evaluate the efficacy and safety of NIS793 in combination with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel and placebo in first-line metastatic pancreatic ductal adenocarcinoma (mPDAC).

This study aims to explore whether blockade of Transforming Growth Factor ß (TGFß) in combination with gemcitabine/nab-paclitaxel can reduce fibrosis in PDAC, restore chemo-sensitivity and ultimately lead to improvements in overall survival (OS) and other clinically relevant outcomes.
Trial website
https://clinicaltrials.gov/study/NCT04935359
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04935359