An open label phase II study to find out if the drug PDR001 is safe and has beneficial effects in patient who have advanced or metastatic non-functional neuroendocrine tumors of pancreatic, gastrointestinal, or thoracic origins and have progressed on prior treatment
- Conditions
- Advanced neuroendocrine tumor (NET) of pancreatic, GI or lung originMedDRA version: 19.1Level: PTClassification code 10052399Term: Neuroendocrine tumourSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-002522-36-FR
- Lead Sponsor
- ovartis Pharma AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 90
1. Written informed consent must be obtained prior to any screening procedures
2. Adult males or females = 18 years at screening.
3. Pathologically confirmed, well-differentiated (G1 or G2) based on local pathologist report,
advanced (unresectable or metastatic), non-functional neuroendocrine tumor of GI,
pancreatic or thoracic (including lung and thymus) origin.
4. No history of, and no active symptoms related to carcinoid syndrome.
5. Patients must have received prior treatment for advanced disease:
? Thoracic (lung and thymus origin) cohort:
? Thymus origin: at least one prior systemic therapy according to investigator’s
choice
? Lung origin: at least one prior systemic therapy is required, which must include
everolimus.
? GI cohort: at least two prior systemic regimens, which must include everolimus. Prior
systemic therapies may include: somatostatin analogs, PRRT, and chemotherapy
? pNET cohort: at least two prior systemic regimens, which must include everolimus or
sunitinib. Prior systemic therapies may include: somatostatin analogs, PRRT, and
chemotherapy
Note: Prior treatment with interferon alpha is allowed provide that it is not the last
treatment received prior to study entry
6. Radiological documentation of 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 one year apart.
7. At least one measurable lesion assessed by CT and/or MRI according to RECIST 1.1.
Note: Any lesions which have been subjected to percutaneous therapies or radiotherapy
should not be considered measurable, unless the lesion has clearly progressed since the
procedure.
8. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
9. Patients must be willing to provide biopsy material for the purpose of biomarker analysis
that was collected following the diagnosis of metastatic disease. The tumor sample must
be collected from a metastatic site not previously irradiated and should preferably be
taken within 6 months but not more than 1 year prior to start of study treatment.
10. Women of childbearing potential must have had a negative serum pregnancy test within
72 hours prior to the start of study treatment. Highly effective contraception must be used
while on study.
11. Patient is deemed by the investigator to have the ability and means to be compliant with
the protocol (treatment and follow-up).
12. Patient must meet the following laboratory values at the screening visit:
? Absolute Neutrophil Count =1.5 x 109/L
? Platelets =75 x 109/L
? Hemoglobin (Hgb) =9 g/dL
? Serum creatinine <1.5 mg/dL
? Total bilirubin =1.5 x ULN
? Aspartate transaminase (AST) = 3.0 x ULN, except for patients with liver metastasis,
if AST =5.0 x ULN
? Alanine transaminase (ALT) = 3.0 x ULN, except for patients with liver metastasis, if
ALT =5.0 x ULN
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 60
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30
1. Poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma,
adenocarcinoid, goblet cell carcinoid, large cell neuroendocrine carcinoma and small cell
carcinoma.
2. Pretreatwith interferon as last treatment prior to start of study treatment
3. Prior treatment for study indication
4. Systemic chronic steroid therapy (= 10mg/day prednisone or equivalent) or any
immunosuppressive therapy 7 days prior to planned date for first dose of study treatment.
5. Any untreated central nervous system (CNS) lesion.
6. Use of hematopoietic colony-stimulating growth factors (e.g. G-CSF, GM-CSF, M-CSF),
thrombopoietin mimetics or erythroid stimulating agents = 2 weeks prior to the first dose
of study treatment.
7. Malignant disease, other than that being treated in this study.
8. Major surgery, open biopsy, or significant traumatic injury within 2 weeks prior to start of
study treatment.
9. Anticipation of the need for major surgical procedure during the course of the study
10. Radiation therapy within 4 weeks prior to start of study treatment
11. Hepatic intra-arterial embolization within the last 6 months.
12. History of severe hypersensitivity reactions to other monoclonal antibodies
13. Impaired cardiac function or clinically significant cardiac disease, including any of the
following:
14. Active, known or suspected autoimmune disease or a documented history of autoimmune
disease, including ulcerative colitis and Crohn’s disease
15. Active infection requiring systemic antibiotic therapy.
16. Known history of testing positive for Human Immunodeficiency Virus (HIV) infection.
17. Patients with active Hepatitis B infection (HBsAg positive) will be excluded.
18. Patients with positive test for hepatitis C ribonucleic acid (HCV RNA)..
19. Any medical condition that would, in the investigator’s judgment, prevent the patient’s
participation in the clinical study due to safety concerns, compliance with clinical study
procedures or interpretation of study results.
20. Use of any live vaccines against infectious diseases within 4 weeks of initiation of study
treatment.
21. Presence of = CTCAE grade 2 toxicity (except alopecia, peripheral neuropathy, and
ototoxicity, which are exclusion criteria if = CTCAE grade 3) due to prior cancer therapy.
22. Not able to understand and to comply with study instructions and requirements.
23. Pregnant or nursing (lactating) women confirmed by a positive hCG laboratory test within
72 hours prior to initiating study treatment. Note: Low levels of hCG may also be
considered a tumor marker, therefore if low hCG levels are detected, another blood sample
at least 4 days later must be taken to assess the kinetics of the increase and transvaginal
ultrasound must be performed to rule out pregnancy.
24. Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant, unless they are using highly effective methods of contraception
during dosing and for 150 days after stopping treatment with PDR001. Highly effective
contraception methods include:
a. Total abstinence (when this is in line with the preferred and usual lifestyle of the
patient). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation
methods) and withdrawal are not acceptable methods of contraception
b. Female sterilization (have had surgical bilateral oophorectomy with or without
hysterectomy), total hysterectomy, or tubal ligation a
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method