Primary: To estimate the antitumor activity (assessed as overall response rate) of PDR001 as a single agent in patients with non-functional neuro-endocrine tumors (NET).Secondary: To estimate efficacy (duration of response) of PDR001. Safety and…
ID
Source
Brief title
Condition
- Malignant and unspecified neoplasms gastrointestinal NEC
- Endocrine neoplasms malignant and unspecified
- Respiratory tract neoplasms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Overall response rate.
Secondary outcome
Duration of response. Adverse events, additional efficacy parameters per
Resist, CgA and NSE, PK parameters, quality of life, immunogenicity.
Background summary
PDR001 is a high-affinity, ligand-blocking, humanized anti-PD-1 IgG4 antibody
that blocks the binding of PD-L1 and PD-L2 to PD-1. PDR001 shows functional
activity in vitro/ex vivo. In the mean time 11 early phase studies with PDR001
as a monotherapy or in combination with LAG525 (an anti-LAG3 antibody) are
ongoing. By the end of March 2016, a total of 58 patients had been treated in
the first in human study. No patient experienced a dose limiting toxicity and
the toxicity profile appears to be similar to that of marketed inhibitors of
PD-1. The PK data support the use of flat dosing for PDR001 of 400 mg every 4
weeks for monotherapy studies.
Inhibitors of the PD-1/PD-L1 interaction are well tolerated and active across a
range of cancer types.
In this phase II study the safety and efficacy of PDR001 will be assessed in
neuro-endocrine tumors in the pancreas, GI-tract and chest.
Study objective
Primary:
To estimate the antitumor activity (assessed as overall response rate) of
PDR001 as a single agent in patients with non-functional neuro-endocrine tumors
(NET).
Secondary:
To estimate efficacy (duration of response) of PDR001. Safety and tolerability,
additional efficacy
Study design
Multicenter phase II open-label non-comparative study.
PDR001 intravenous infusion 400 mg in 30 minutes (if indicated up to 2 hours)
every 4 weeks.
The study treatment will be administered in cycles of 4 weeks.
Treatment until disease progression or unacceptable adverse reaction. Maximum
duration of treatment 2 years.
Approx. 90 subjects. 3 cohorts of approx. 30 subjects (based on location of the
primary tumor).
Intervention
Treatment with PDR001.
Study burden and risks
Risk: Adverse effects of PDR001.
Burden: Cycles of 4 weeks. Visits on day 1 of every cycle. Visit duration
mostly 1-4 hours.
IV infusions of PDR001 on day 1 of every cycle (250 ml per occasion). Duration
standard 0,5 hour (up to 2 hours is accepted).
Physical examination: once per cycle.
Blood tests (15ml/occasion): once per cycle.
Blood for biomarkers: 120 ml in total, PK 40 ml in total, immunogenicity 60 ml
in total
ECG: every 12 weeks.
CT-/MRI scan: every 8-12 weeks.
Questionnaires EORTC QLQ-C30 and EQ-5D every 8-12 weeks.
Archival tumor tissue (if needed new biopsy).
Optional tumor biopsies during treatment and at disease progression.
Optional use of the remaining blood and tissue for future research.
Raapopseweg 1
Arnhem 6824 DP
NL
Raapopseweg 1
Arnhem 6824 DP
NL
Listed location countries
Age
Inclusion criteria
* Female and male patients * 18 years old.
* Pathologically confirmed, advanced (unresectable or metastatic):
- well-differentiated (G1 or G2) unresectable or metastatic 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
* Criteria for the 4 cohorts (based on location of primary tumor): see protocol, page 35.
* Radiological documentation of disease progression while on/or after the last treatment, see protocol page 35/36 for details.
* At least one measurable lesion assessed by CT and/or MRI according to RECIST 1.1.
* ECOG performance status 0-1-2.
* Adequate contraception.
* Tumor biopsy material mist be provided for all patients for the purpose of biomarker analysis:
- well-differentiated (G1/2) NET: collected from the metastic site, not previously irradiated, preferably be taken within 6 months but not more than 24 months prior start study treatment
- poorly differentiated GEP-NEC: collected from the primary tumor of from metastartic site, not previously irradiated, taken not more tha 24 months prior start study treatment
Update Am2:
- life expectancy of at least 3 months
Exclusion criteria
* Well differentiated grade 3 neuro-endocrine tumors; poorly differentiated neuro-endocrine carcinoma of any origin (other than GEP-NEC); including NEC of unknown origin, adenocarcinoid, goblet cell carcinoid, large cell neuro-endocrine carcinoma and small cell carcinoma.
* Pretreatment with interferon as last treatment prior to start of study treatment.
* Prior treatment for study indication with antibodies or immunotherapy, PRRT, systemische antineoplastic therapy, TKIs, PD-1 or PD-L1 directed therapy. Cryoablation, radiofrequency ablation, or trans-arterial chemo-embolization of hepatic metastases. See for details and washout periods protocol page 37.
* 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.
* Pregnancy, lactation, insufficient contraception for females of childbearing potential.
* Autoimmune disease that has required systemic treatment. Stable and adequate controlled endocrinopathies requiering replacement therapy are not considered as systemic treatment and therefore are allowed.
* Known history or current interstitial lung disease or nonb-infections pneumonitis
* Use of somatostatin analogs or any other medications administered to control active symtoms related to carcinoid syndrome during the last 3 months prior to start of study treatment
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2016-002522-36-NL |
| ClinicalTrials.gov | NCT02355069 |
| CCMO | NL60098.031.16 |