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Trial record 57 of 904 for:    Advanced | Neuroendocrine Tumors

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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02955069
Recruitment Status : Completed
First Posted : November 4, 2016
Last Update Posted : June 26, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
This is a study 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 have progressed on prior treatment.

Condition or disease Intervention/treatment Phase
Well-differentiated Non-functional NET of Thoracic Origin Well-differentiated Non-functional NET of Gastrointestinal Origin Well-differentiated Non-functional NET of Pancreatic Origin Poorly-differentiated Gastroenteropancreatic Neuroendocrine Carcinoma Drug: PDR001 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 116 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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.
Actual Study Start Date : February 14, 2017
Actual Primary Completion Date : August 10, 2018
Actual Study Completion Date : May 13, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: PDR001
PDR001 administered via intravenous infusion once every 4 weeks.
Drug: PDR001
PDR001 is a high-affinity, ligand-blocking, humanized IgG4 antibody directed against Programmed Death-1 (PD-1) receptor that blocks the binding of PD-L1 and PD-L2. PDR001 dose is 400 mg infusion every 4 weeks.




Primary Outcome Measures :
  1. Overall response rate by RECIST 1.1 and as per Blinded Independent Central Review (BIRC). [ Time Frame: From baseline up to approximately 1.5 years (through database cut-off date of 10Aug2018) ]
    Overall response rate is defined as the proportion of patients with best overall response (BOR) of complete response (CR) or partial response (PR), according to blinded independent review committee (BIRC) radiological assessment by RECIST 1.1


Secondary Outcome Measures :
  1. Duration of response by RECIST 1.1 and as per BIRC [ Time Frame: 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 (through database cut-off date of 10Aug2018) ]
    The time between the date of first documented response (CR or PR) and the date of first documented disease progression or death due to underlying cancer by RECIST 1.1 and as per BIRC

  2. Frequency and severity of Adverse [ Time Frame: From baseline to 150 days after end of treatment, approximately 3 years ]
    Safety will be determined by frequency and severity of adverse events (AEs) and laboratory abnormalities

  3. Disease Control Rate by RECIST 1.1 and as per BIRC [ Time Frame: From baseline up to approximately 1.5 years (through database cut-off date of 10Aug2018) ]
    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

  4. Time to response by RECIST 1.1 and as per BIRC [ Time Frame: From baseline to the first documented response, assessed up to approximately 1.5 years (through database cut-off date of 10Aug2018) ]
    Time to response (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 will be evaluated according to RECIST 1.1 and as per BIRC

  5. Progression-free survival by RECIST 1.1 and as per BIRC [ Time Frame: 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 (through database cut-off date of 10Aug2018) ]
    Progression-free survival (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 will be evealuated according to RECIST 1.1 and as per BIRC.

  6. Immune related Overall Response Rate (irORR) by irRECIST and as per BIRC [ Time Frame: From baseline up to approximately 1.5 years (through database cut-off date of 10Aug2018) ]
    Immune related Overall Response Rate (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

  7. Immune related Duration of Response (irDoR) by irRECIST and as per BIRC [ Time Frame: From the date of first documented confirmed response (irCR or irPR) until the first documented progression, assessed up to approximately 1.5 years (through database cut-off date of 10Aug2018) ]
    The time from first documentation of irCR or irPR until the time of first documentation of progression per irRECIST based on BIRC assessment

  8. Immune related Time to Response (irTTR) by irRECIST and as per BIRC [ Time Frame: From baseline to the first documented response, assessed up to approximately 1.5 years (thorugh database cut-off date of 10Aug2018) ]
    Time between date of start of treatment until first documented response (confirmed irCR or irPR) by irRECIST and as per BIRC

  9. Immune related Disease Control Rate (irDCR) by irRECIST and as per BIRC [ Time Frame: From baseline up to approximately 1.5 years (through database cut-off date of 10Aug2018) ]
    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

  10. Immune related Progression Free Survival (irPFS) by irRECIST and as per BIRC [ Time Frame: 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 (through database cut-off date of 10Aug2018) ]
    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.

  11. Overall survival [ Time Frame: From baseline until death due to any cause, assessed up to 3 years ]
    Overall survival is defined as the time from the start of treatment date to the date of death, due to any cause

  12. Changes from baseline in Chromogranin A (CgA) levels [ Time Frame: Baseline, day 1 of each cycle and end of treatment, through database cut-off date of 10Aug2018, approx. 1.5 years. Cycle=28 days. ]
    The biochemical response will be assessed using the change from baseline for CgA levels.

  13. Change from baseline in neuron specific enolase (NSE) levels [ Time Frame: Baseline, day 1 of each cycle and end of treatment, through database cut-off date of 10-Aug-2018, approximately 1.5 years. Each cycle duration is 28 days. ]
    The biochemical response will be assessed using the change from baseline for NSE levels.

  14. PDR001 plasma concentration [ Time Frame: 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, end of treatment,30 and 150-day post-treatment, through cut-off date: 10Aug2018.Cycle=28 days ]
    Blood samples will be taken to evaluate the pharmacokinetics by assessing plasma concentration of PDR001

  15. Change from baseline in EORTC QLQ-C30 score [ Time Frame: Baseline, every 8 weeks from Cycle 3 Day 1 for the first 13 cycles and every 12 weeks from Cycle 13 Day 1 thereafter, end of treatment, 30-day post-treatment and until confirmed progression (through cut-off date 10Aug2018 approx.1.5 years). Cycle=28 days ]
    EORTC QLQ-C30 is the European Organization for Research and Treatment of Cancer, Quality of Life (QoL) Questionnaire. The EORTC QLQ-C30 contains 30 items and is composed of both multi-item scales and single-item measures. These include five functional scales (physical, role, emotional, cognitive and social functioning), three symptom scales (fatigue, nausea/vomiting, and pain), six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/QoL scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning; a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems

  16. Change from baseline in EQ-5D-5L score [ Time Frame: Baseline, every 8 weeks from Cycle 3 Day 1 for the first 13 cycles and every 12 weeks from Cycle 13 Day 1 thereafter, end of treatment, 30-day post-treatment and until confirmed progression (through cut-off date 10Aug2018 approx.1.5 years). Cycle=28 days ]
    EQ-5D-5L descriptive system comprises of 5 dimensions-mobility,self-care,usual activities,pain/discomfort & anxiety/depression.Each dimension has 5 levels:not at all(level 1),mild(level 2),moderate(level 3),severe(level 4),extreme/leading to incapacity(level 5),with highest level corresponding to worst outcome.Subjects have to indicate their health state by choosing the appropriate level from each dimension.The 5 digit health states obtained for each dimension will be converted into a single mean index value using the EQ-5D-5L crosswalk index value calculator as recommended by EuroQol group.In the EQ-VAS,subjects have to record their health state on a scale ranging from 0 (worst imaginable health state) to 100 (best imaginable health state).A mean of this health state will be recorded.

  17. Antidrug antibodies (ADA) prevalence at baseline [ Time Frame: Baseline ]
    Blood samples will be taken to evaluate the immunogenicity bya ssessing anti-drug antibodies (ADA) prevalence at baseline

  18. ADA incidence on-treatment [ Time Frame: 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, end of treatment,30 and 150-day post-treatment, through cut-off date: 10Aug2018.Cycle=28 days ]
    Blood samples will be taken to evaluate the immunogenicity by assessing anti-drug antibodies (ADA) incidence on-treatment



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 depends 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.

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.
  • 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 PD-1- or 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 may apply


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02955069


Locations
Show Show 38 study locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02955069    
Other Study ID Numbers: CPDR001E2201
2016-002522-36 ( EudraCT Number )
First Posted: November 4, 2016    Key Record Dates
Last Update Posted: June 26, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

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.


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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Advanced or metastatic
NET
pNET
GI NET
thoracic NET
GEP-NEC
Additional relevant MeSH terms:
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Carcinoma
Neuroendocrine Tumors
Carcinoma, Neuroendocrine
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Adenocarcinoma