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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/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)
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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.
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Secondary ID [1]
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2016-002522-36
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Secondary ID [2]
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CPDR001E2201
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Well-differentiated Non-functional NET of Thoracic Origin
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Well-differentiated Non-functional NET of Gastrointestinal Origin
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Well-differentiated Non-functional NET of Pancreatic Origin
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Poorly-differentiated Gastroenteropancreatic Neuroendocrine Carcinoma
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Condition category
Condition code
Cancer
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Non melanoma skin cancer
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Cancer
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Kidney
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Cancer
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Neuroendocrine tumour (NET)
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Intervention/exposure
Study type
Interventional
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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.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Overall Response Rate (ORR) by RECIST 1.1 and as Per Blinded Independent Central Review (BIRC).
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Assessment method [1]
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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.
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Timepoint [1]
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From baseline up to approximately 1.5 years
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Secondary outcome [1]
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Duration of Response (DOR) by RECIST 1.1 and as Per BIRC
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Assessment method [1]
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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.
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Timepoint [1]
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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
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Secondary outcome [2]
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Disease Control Rate by RECIST 1.1 and as Per BIRC
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Assessment method [2]
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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.
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Timepoint [2]
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From baseline up to approximately 1.5 years
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Secondary outcome [3]
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Time to Response (TTR) by RECIST 1.1 and as Per BIRC
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Assessment method [3]
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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.
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Timepoint [3]
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From baseline to the first documented response, assessed up to approximately 1.5 years
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Secondary outcome [4]
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Progression-free Survival (PFS) by RECIST 1.1 and as Per BIRC
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Assessment method [4]
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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.
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Timepoint [4]
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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
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Secondary outcome [5]
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Immune Related Overall Response Rate (irORR) by irRECIST and as Per BIRC
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Assessment method [5]
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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).
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Timepoint [5]
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From baseline up to approximately 1.5 years
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Secondary outcome [6]
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Immune Related Duration of Response (irDoR) by irRECIST and as Per BIRC.
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Assessment method [6]
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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
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Timepoint [6]
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From the date of first documented confirmed response (irCR or irPR) until the first documented progression, assessed up to approximately 1.5 years
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Secondary outcome [7]
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Immune Related Time to Response (irTTR) by irRECIST and as Per BIRC
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Assessment method [7]
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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.
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Timepoint [7]
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From baseline to the first documented response, assessed up to approximately 1.5 years
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Secondary outcome [8]
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Immune Related Disease Control Rate (irDCR) by irRECIST and as Per BIRC
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Assessment method [8]
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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.
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Timepoint [8]
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From baseline up to approximately 1.5 years
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Secondary outcome [9]
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Immune Related Progression Free Survival (irPFS) by irRECIST and as Per BIRC
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Assessment method [9]
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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.
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Timepoint [9]
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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
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Secondary outcome [10]
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Overall Survival (OS)
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Assessment method [10]
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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.
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Timepoint [10]
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From baseline until death due to any cause, assessed up to approx. 3 years
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Secondary outcome [11]
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Changes From Baseline in Chromogranin A (CgA) Levels
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Assessment method [11]
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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.
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Timepoint [11]
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Baseline, day 1 of each cycle from Cycle 2 to end of treatment, assessed up to approx. 1.5 years. Cycle=28 days.
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Secondary outcome [12]
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Change From Baseline in Neuron Specific Enolase (NSE) Levels
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Assessment method [12]
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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.
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Timepoint [12]
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Baseline, day 1 of each cycle from Cycle 2 to end of treatment, assessed up to approx. 1.5 years. Cycle= 28days
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Secondary outcome [13]
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PDR001 Plasma Concentration
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Assessment method [13]
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Blood samples will be taken to evaluate the pharmacokinetics by assessing plasma concentration of PDR001 at selected time points
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Timepoint [13]
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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
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Secondary outcome [14]
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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
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Assessment method [14]
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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.
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Timepoint [14]
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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
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Secondary outcome [15]
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Change From Baseline in EQ-5D-5L Index Score
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Assessment method [15]
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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.
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Timepoint [15]
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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
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Secondary outcome [16]
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PDR001 Anti-drug Antibodies (ADA) Prevalence at Baseline
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Assessment method [16]
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ADA prevalence at baseline was calculated as the proportion of participants who had an ADA positive result at baseline
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Timepoint [16]
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Baseline
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Secondary outcome [17]
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PDR001 ADA Incidence On-treatment
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Assessment method [17]
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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)
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Timepoint [17]
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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
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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.
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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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
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Study design
Purpose of the study
Treatment
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Allocation to intervention
N/A
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Single group
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Other design features
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Phase
Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
14/02/2017
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
13/05/2020
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Sample size
Target
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Accrual to date
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Final
116
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Recruitment in Australia
Recruitment state(s)
NSW
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Recruitment hospital [1]
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Novartis Investigative Site - St Leonards
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Recruitment postcode(s) [1]
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2065 - St Leonards
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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California
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Country [2]
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United States of America
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State/province [2]
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Colorado
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Country [3]
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United States of America
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State/province [3]
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Florida
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Country [4]
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United States of America
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State/province [4]
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Minnesota
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Country [5]
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United States of America
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State/province [5]
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New York
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Country [6]
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United States of America
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State/province [6]
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Texas
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Country [7]
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Austria
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State/province [7]
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Wien
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Country [8]
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Belgium
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State/province [8]
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Brussels
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Country [9]
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Belgium
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State/province [9]
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Leuven
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Country [10]
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Canada
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State/province [10]
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Ontario
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Country [11]
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Canada
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State/province [11]
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Quebec
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Country [12]
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France
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State/province [12]
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Lyon
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Country [13]
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France
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State/province [13]
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Marseille
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Country [14]
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France
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State/province [14]
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Toulouse Cedex 4
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Country [15]
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Germany
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State/province [15]
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Erlangen
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Country [16]
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Germany
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State/province [16]
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Essen
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Country [17]
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Germany
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State/province [17]
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Mainz
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Country [18]
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Germany
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State/province [18]
0
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Marburg
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Country [19]
0
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Italy
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State/province [19]
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BO
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Country [20]
0
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Italy
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State/province [20]
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FC
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Country [21]
0
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Italy
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State/province [21]
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MI
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Country [22]
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Italy
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State/province [22]
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RM
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Country [23]
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Italy
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State/province [23]
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Napoli
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0
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Japan
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State/province [24]
0
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Aichi
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0
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Japan
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State/province [25]
0
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Chiba
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Country [26]
0
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Japan
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State/province [26]
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Fukuoka
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Country [27]
0
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Japan
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State/province [27]
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Tokyo
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Country [28]
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Netherlands
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State/province [28]
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Amsterdam
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Country [29]
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Spain
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State/province [29]
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Catalunya
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Country [30]
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Spain
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State/province [30]
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Madrid
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Country [31]
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United Kingdom
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State/province [31]
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London
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Novartis Pharmaceuticals
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Address
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Country
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Ethics approval
Ethics application status
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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.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT02955069
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Novartis Pharmaceuticals
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Address
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Novartis Pharmaceuticals
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Country
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Phone
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Fax
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Email
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT02955069
Download to PDF