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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT02955069
Ethics application status
Date submitted
2/11/2016
Date registered
4/11/2016
Date last updated
12/04/2021

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). - ORR is defined as the proportion of patients with best overall response (BOR) of complete response (CR) or partial response (PR), according to BIRC radiological assessment by RECIST 1.1.
CR: disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.
PR: at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
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 - DOR is defined as the time between the date of first documented response (CR or PR) and the date of first documented disease progression by RECIST 1.1 and as per BIRC or death due to underlying cancer. For DOR analysis, participants continuing without progression or death due to underlying cancer were censored at the date of their last adequate tumor assessment. An adequate tumour assessment is a tumour assessment with an overall response other than unknown.
CR: disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.
PR: at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
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 - Disease control rate is defined as the proportion of patients with best overall response of CR, PR or stable disease (SD) according to RECIST 1.1 criteria and as per BIRC.
CR: disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.
PR: at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
SD: neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease.
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 - TTR is defined as the time from the date of start of treatment to the first documented response of either CR or PR, which must be subsequently confirmed. TTR was evaluated according to RECIST 1.1 and as per BIRC.
CR: disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.
PR: at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
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 - PFS is defined as the time from the date of first dose to the date of the first documented radiological progression or death due to any cause. PFS was evaluated according to RECIST 1.1 and as per BIRC. For participants who had not progressed or died at the analysis cut-off date, PFS was censored at the date of the last adequate tumor evaluation date. An adequate tumour assessment is a tumour assessment with an overall response other than unknown.
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 - irORR is the proportion of patients with a best overall response of immune related Complete Response (irCR) or immune related partial response (irPR), according to BIRC assessment by irRECIST.
irCR: Complete disappearance of all measurable and non-measurable lesions. In addition, any pathological lymph nodes must have a reduction in short axis to < 10 mm.
irPR: At least 30% decrease in the total measurable tumor burden (TMTB) compared to baseline and not qualifying for irCR or immune related progressive disease (irPD).
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. - irDOR is defined as the time from first documentation of irCR or irPR until the time of first documentation of progression per irRECIST based on BIRC assessment. Participants continuing without progression or death due to underlying cancer were censored at the date of their last adequate tumor assessment. An adequate tumour assessment is a tumour assessment with an overall response other than unknown for irRECIST.
irCR: Complete disappearance of all measurable and non-measurable lesions. In addition, any pathological lymph nodes must have a reduction in short axis to < 10 mm.
irPR: At least 30% decrease in the TMTB compared to baseline and not qualifying for irPD or irCR
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 - irTTR is defined as the time between date of start of treatment until first documented response (confirmed irCR or irPR) by irRECIST and as per BIRC.
irCR: Complete disappearance of all measurable and non-measurable lesions. In addition, any pathological lymph nodes must have a reduction in short axis to < 10 mm.
irPR: At least 30% decrease in the TMTB compared to baseline and not qualifying for irPD or irCR.
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 - irDCR is defined as the proportion of patients with a best overall response of irCR or irPR or immune related stable disease (irSD) according to irRECIST and as per BIRC.
irCR: Complete disappearance of all measurable and non-measurable lesions. In addition, any pathological lymph nodes must have a reduction in short axis to < 10 mm.
irPR: At least 30% decrease in the TMTB compared to baseline and not qualifying for irPD or irCR.
irSD: Neither a sufficient shrinkage to qualify for irPR or irCR, nor an increase in lesions, or a clear and unequivocal progression of existing nontarget or new non-measurable lesions that would qualify for irPD.
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 - irPFS is defined as the time from date of start of treatment to the date of event defined as the first documented assessment of immune related progression that is confirmed or death due to any cause. If a patient has not had an event, immune related progression-free survival was censored at the date of last adequate tumor assessment. An adequate tumor assessment is a tumor assessment with overall response other than unknown for irRECIST.
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) - OS is defined as the time from the start of treatment date to the date of death, due to any cause. If a patient was not known to have died, then OS was censored at the latest date the patient was known to be alive.
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 - Blood samples were collected for assessment of CgA level. Change from Baseline at a particular visit was calculated as the CgA level at that visit minus Baseline.
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 - Blood samples were collected for assessment of NSE level. Change from Baseline at a particular visit was calculated as the NSE level at that visit minus Baseline.
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 - Blood samples will be taken to evaluate the pharmacokinetics by assessing plasma concentration of PDR001 at selected time points
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 - The EORTC QLQ-C30 is a patient completed 30 item questionnaire that is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, six single items and a global health status/QoL scale. Global health status/QoL response options are 1 to 4. Scores were averaged and transformed to 0 to 100. Higher scores indicate better functioning.
Change from Baseline was calculated by subtracting Baseline value from the selected visit value. A positive change from Baseline indicates improvement.
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 - The EQ-5D-5L descriptive system provides a profile of the participant's health state in 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each of these dimensions, the participant self-assigned a score: from 1 (no problems) to 5 (extreme problems). The 5 digit health states obtained for each dimension was converted into a single mean index value based on the EQ-5D crosswalk value set for the UK using the time trade-off method. This index ranges from -0.594 (worst health) to 1.0 (best health). Change from Baseline was calculated by subtracting Baseline value from the selected visit value. A positive change from baseline indicates improvement.
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 - ADA prevalence at baseline was calculated as the proportion of participants who had an ADA positive result at baseline
Timepoint [16] 0 0
Baseline
Secondary outcome [17] 0 0
PDR001 ADA Incidence On-treatment - ADA incidence on treatment was calculated as the proportion of participants who were treatment-induced ADA positive (post-baseline ADA positive with ADA-negative sample at baseline) and treatment-boosted ADA positive (post-baseline ADA positive with titer that is at least the fold titer change greater than the ADA-positive baseline titer)
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
Gender
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
N/A
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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
This study aimed to investigate 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 progressed on prior treatment.
Trial website
https://clinicaltrials.gov/show/NCT02955069
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
Other publications