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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02955069




Registration number
NCT02955069
Ethics application status
Date submitted
2/11/2016
Date registered
4/11/2016

Titles & IDs
Public title
Study of Efficacy and Safety of PDR001 in Patients With Advanced or Metastatic, Well-differentiated, Non-functional Neuroendocrine Tumors of Pancreatic, Gastrointestinal (GI), or Thoracic Origin or Poorly-differentiated Gastroenteropancreatic Neuroendocrine Carcinoma (GEP-NEC)
Scientific title
An Open Label Phase II Study to Evaluate the Efficacy and Safety of PDR001 in Patients With Advanced or Metastatic, Well-differentiated, Non-functional Neuroendocrine Tumors of Pancreatic, Gastrointestinal (GI), or Thoracic Origin or Poorly-differentiated Gastroenteropancreatic Neuroendocrine Carcinoma (GEP-NEC), That Have Progressed on Prior Treatment.
Secondary ID [1] 0 0
2016-002522-36
Secondary ID [2] 0 0
CPDR001E2201
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Well-differentiated Non-functional NET of Thoracic Origin 0 0
Well-differentiated Non-functional NET of Gastrointestinal Origin 0 0
Well-differentiated Non-functional NET of Pancreatic Origin 0 0
Poorly-differentiated Gastroenteropancreatic Neuroendocrine Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Neuroendocrine tumour (NET)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - PDR001

Experimental: PDR001 - Subjects with advanced or metastatic, well-differentiated, NET of pancreatic, GI, or thoracic origin or poorly-differentiated GEP-NEC, that have progressed on prior treatment were treated with 400mg PDR001 administered via intravenous infusion once every 4 weeks.


Treatment: Drugs: PDR001
PDR001 was administered at a dose of 400 mg via intravenous infusion once every 4 weeks (Q4W). PDR001 was administered on Day 1 of every cycle. Each cycle was 28 days.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Response Rate (ORR) by RECIST 1.1 and as Per Blinded Independent Central Review (BIRC).
Timepoint [1] 0 0
From baseline up to approximately 1.5 years
Secondary outcome [1] 0 0
Duration of Response (DOR) by RECIST 1.1 and as Per BIRC
Timepoint [1] 0 0
From the date of first documented response (CR or PR) until the first documented disease progression or death, whichever comes first, assessed up to approximately 1.5 years
Secondary outcome [2] 0 0
Disease Control Rate by RECIST 1.1 and as Per BIRC
Timepoint [2] 0 0
From baseline up to approximately 1.5 years
Secondary outcome [3] 0 0
Time to Response (TTR) by RECIST 1.1 and as Per BIRC
Timepoint [3] 0 0
From baseline to the first documented response, assessed up to approximately 1.5 years
Secondary outcome [4] 0 0
Progression-free Survival (PFS) by RECIST 1.1 and as Per BIRC
Timepoint [4] 0 0
From baseline until the date of the first documented radiological progression or death due to any cause, whichever comes first, assessed up to approximately 1.5 years
Secondary outcome [5] 0 0
Immune Related Overall Response Rate (irORR) by irRECIST and as Per BIRC
Timepoint [5] 0 0
From baseline up to approximately 1.5 years
Secondary outcome [6] 0 0
Immune Related Duration of Response (irDoR) by irRECIST and as Per BIRC.
Timepoint [6] 0 0
From the date of first documented confirmed response (irCR or irPR) until the first documented progression, assessed up to approximately 1.5 years
Secondary outcome [7] 0 0
Immune Related Time to Response (irTTR) by irRECIST and as Per BIRC
Timepoint [7] 0 0
From baseline to the first documented response, assessed up to approximately 1.5 years
Secondary outcome [8] 0 0
Immune Related Disease Control Rate (irDCR) by irRECIST and as Per BIRC
Timepoint [8] 0 0
From baseline up to approximately 1.5 years
Secondary outcome [9] 0 0
Immune Related Progression Free Survival (irPFS) by irRECIST and as Per BIRC
Timepoint [9] 0 0
From baseline until the date of the first documented immune related progression or death due to any cause, whichever comes first, assessed up to approximately 1.5 years
Secondary outcome [10] 0 0
Overall Survival (OS)
Timepoint [10] 0 0
From baseline until death due to any cause, assessed up to approx. 3 years
Secondary outcome [11] 0 0
Changes From Baseline in Chromogranin A (CgA) Levels
Timepoint [11] 0 0
Baseline, day 1 of each cycle from Cycle 2 to end of treatment, assessed up to approx. 1.5 years. Cycle=28 days.
Secondary outcome [12] 0 0
Change From Baseline in Neuron Specific Enolase (NSE) Levels
Timepoint [12] 0 0
Baseline, day 1 of each cycle from Cycle 2 to end of treatment, assessed up to approx. 1.5 years. Cycle= 28days
Secondary outcome [13] 0 0
PDR001 Plasma Concentration
Timepoint [13] 0 0
Cycle(C)1 Day(D)1 pre-dose and 30min post-infusion,C2D1 Pre-dose,C3D1 Pre-dose and 30min post-infusion,D1 pre-dose from C4 to C13, assessed up to approx. 1.5 years.Cycle=28 days
Secondary outcome [14] 0 0
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status/Quality of Life Score
Timepoint [14] 0 0
Baseline, every 8 weeks from Cycle 3 Day 1 for the first 13 cycles and every 12 weeks from Cycle 13 Day 1 thereafter and end of treatment, assessed up to approx. 1.5 years. Cycle=28 days
Secondary outcome [15] 0 0
Change From Baseline in EQ-5D-5L Index Score
Timepoint [15] 0 0
Baseline, every 8 weeks from Cycle 3 Day 1 for the first 13 cycles and every 12 weeks from Cycle 13 Day 1 thereafter, and end of treatment, assessed up to approx.1.5 year. Cycle=28 days
Secondary outcome [16] 0 0
PDR001 Anti-drug Antibodies (ADA) Prevalence at Baseline
Timepoint [16] 0 0
Baseline
Secondary outcome [17] 0 0
PDR001 ADA Incidence On-treatment
Timepoint [17] 0 0
Cycle(C)1 Day(D)1 pre-dose and 30min post-infusion,C2D1 Pre-dose,C3D1 Pre-dose and 30min post-infusion,D1 pre-dose from C4 to C13 and every 6 cycles until C25, and end of treatment, assessed up to approx. 1.5 years. Cycle=28 days

Eligibility
Key inclusion criteria
* Pathologically confirmed, advanced (unresectable or metastatic):
* Well-differentiated (G1 or G2) based on local pathology report, non-functional neuroendocrine tumor of GI, pancreatic or thoracic (including lung and thymus) origin.
* Poorly-differentiated GEP-NEC based on local pathology report
* No active symptoms related to carcinoid syndrome during the last 3 months prior to start of study treatment.
* Patients must have been pretreated for advanced disease - the number of prior systemic therapy/regimen depended on which origin for NET and for GEP-NEC
* Tumor biopsy material must be provided for all patients for the purpose of biomarker analysis
* Radiological documentation of disease progression:
* Well-differentiated NET group: Disease progression while on/or after the last treatment, and this progression must have been observed within 6 months prior to start of study treatment (i.e. maximum of 24 weeks from documentation of progression until study entry). Disease must show evidence of radiological disease progression based on scans performed not more than 12 months apart.
* Poorly-differentiated GEP-NEC group: Disease progression while on or after prior treatment.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Well-differentiated grade 3 neuroendocrine tumors; poorly-differentiated neuroendocrine carcinoma of any origin (other than GEP-NEC); including NEC of unknown origin, adenocarcinoid, and goblet cell carcinoid
* Pretreatment with interferon as last treatment prior to start of study treatment.
* Prior treatment for study indication with:
* Antibodies or immunotherapy within 6 weeks before the first dose of study treatment.
* Peptide Radionuclide Receptor Therapy (PRRT) administered within 6 months of the first dose.
* Systemic antineoplastic therapy
* Tyrosine kinase inhibitors within 14 days or 5 half-lives, whichever is longer, before the first dose of study treatment.
* Prior Programmed Death-1 (PD-1) or Programmed Death-Ligand 1 (PD-L1) directed therapy.
* Cryoablation, radiofrequency ablation, or trans-arterial embolization of hepatic metastases
* History of severe hypersensitivity reactions to other monoclonal antibodies which in the opinion of the investigator may pose an increased risk of a serious infusion reaction.

Other inclusion/exclusion criteria might apply

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
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
Single group
Other design features
Phase
Phase 2
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
14/02/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
13/05/2020
Sample size
Target
Accrual to date
Final
116
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Novartis Investigative Site - St Leonards
Recruitment postcode(s) [1] 0 0
2065 - St Leonards
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
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
Minnesota
Country [5] 0 0
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
Austria
State/province [7] 0 0
Wien
Country [8] 0 0
Belgium
State/province [8] 0 0
Brussels
Country [9] 0 0
Belgium
State/province [9] 0 0
Leuven
Country [10] 0 0
Canada
State/province [10] 0 0
Ontario
Country [11] 0 0
Canada
State/province [11] 0 0
Quebec
Country [12] 0 0
France
State/province [12] 0 0
Lyon
Country [13] 0 0
France
State/province [13] 0 0
Marseille
Country [14] 0 0
France
State/province [14] 0 0
Toulouse Cedex 4
Country [15] 0 0
Germany
State/province [15] 0 0
Erlangen
Country [16] 0 0
Germany
State/province [16] 0 0
Essen
Country [17] 0 0
Germany
State/province [17] 0 0
Mainz
Country [18] 0 0
Germany
State/province [18] 0 0
Marburg
Country [19] 0 0
Italy
State/province [19] 0 0
BO
Country [20] 0 0
Italy
State/province [20] 0 0
FC
Country [21] 0 0
Italy
State/province [21] 0 0
MI
Country [22] 0 0
Italy
State/province [22] 0 0
RM
Country [23] 0 0
Italy
State/province [23] 0 0
Napoli
Country [24] 0 0
Japan
State/province [24] 0 0
Aichi
Country [25] 0 0
Japan
State/province [25] 0 0
Chiba
Country [26] 0 0
Japan
State/province [26] 0 0
Fukuoka
Country [27] 0 0
Japan
State/province [27] 0 0
Tokyo
Country [28] 0 0
Netherlands
State/province [28] 0 0
Amsterdam
Country [29] 0 0
Spain
State/province [29] 0 0
Catalunya
Country [30] 0 0
Spain
State/province [30] 0 0
Madrid
Country [31] 0 0
United Kingdom
State/province [31] 0 0
London

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT02955069