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Dose Escalation Study of Immunomodulatory Nanoparticles
Bu çalışma, PRECIOUS-01 adlı immünomodülatör (bağışıklık sistemini düzenleyen) nanopartikül tedavisinin, standart tedavi seçeneği kalmamış ilerlemiş ve/veya metastatik solid tümörü (advanced/metastatic solid tumor) olan hastalardaki güvenli dozunu araştırıyor. Çalışmaya, tümörü NY-ESO-1 açısından pozitif olan, 18 yaş ve üzeri yetişkinler alınmaktadır. Çalışma Faz 1 aşamasında yürütülmüş; şu an katılımcı almamakta ancak devam etmektedir (active, not recruiting).
Yukarıdaki özet, resmî kaydın sade dile aktarılmış halidir. Orijinal İngilizce başlık referans için gösterilir.
Kriterler ClinicalTrials.gov kaydından orijinal İngilizce haliyle alınmıştır. Uygunluk kararını yalnızca deneyi yürüten ekip verebilir.
Inclusion Criteria:
1. Age 18 years or older at time of signing informed consent.
2. Performance status (ECOG 0 or 1).
3. Estimated life expectancy of at least 6 months.
4. Histologically or cytologically confirmed advanced and /or metastatic solid tumor with progressive disease at baseline, for whom no standard treatment is available.
5. IHC-confirmed NY-ESO-1 positivity prior to screening (cut-off value: 1% positive cells) on (archival) tumor tissue, per local laboratory guidelines.
6. Subject with evaluable disease per RECIST v1.1.
7. Adequate hematologic, renal and liver function as defined by laboratory values performed within 14 days of start of treatment:
1. Hemoglobin (Hb) ≥ 6 mmol/L;
2. Absolute Lymphocyte Count (ALC) \> 0.8 x 109/L;
3. Absolute Neutrophil Count (ANC) ≥ 1.5 × 109/L;
4. Platelet count \> 100 x 109/L;
5. Creatinine level within normal institutional limit;
6. Serum bilirubin \< 25 μmol/L;
7. Serum Lactic Acid Dehydrogenase (LDH) ≤ Upper Limit of Normal range (ULN);
8. Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Alanine Aminotransferase (ALT) ≤ ULN unless related to liver metastasis (in which case levels should be \< 3 ULN).
8. Previous therapy-derived toxicities should be resolved to Grade \< 2 according to CTCAE v5.0, with exceptions for alopecia.
9. All subjects of childbearing potential (defined as \< 2 years after last menstruation or not surgically sterile) must have a negative highly sensitive pregnancy test at screening (urine/serum) and agree to use a highly effective method for contraception according to the EU Clinical Trial Facilitation Group guidance from time of signing the informed consent form (ICF) until at least 120 days after the last administration of PRECIOUS-01. The partners of subjects with childbearing potential must also apply contraceptive methods, and are recommended not to donate sperm.
10. Before registration, ability of subject to give written informed consent according to International Council for Harmonisation (ICH) Good Clinical Practice (GCP), and national rules/local regulations.
11. Expected adequacy of follow-up.
Exclusion Criteria:
1. Second malignancy in the previous 2 years, with the exception of adequately treated in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin,
2. Clinical suspicion or radiological evidence of active brain metastases. Patients with brain metastases that have been treated previously and are proven stable (computed tomography \[CT\] or magnetic resonance imaging \[MRI\] \< 30 days) and without steroids for \> 3 months are allowed.
3. Subjects with thromboembolic events within the past year.
4. Subjects on any other anticancer therapy (cytotoxic, biologic or investigational agents), unless at least 4 weeks (or 5 half-lives, whichever is shorter, 6 weeks for mitomycin-C or nitrosoureas), have elapsed since the last dose before the first administration of PRECIOUS-01. At least 4 weeks should have elapsed since receiving palliative radiotherapy. Chronic treatment with non-investigational gonadotropin-releasing hormone analogs or other hormonal or supportive care is permitted.
5. Subjects with major surgery within 4 weeks before initiating treatment or with minor surgical procedure within 7 days before initiating treatment (except for port-a-cath or central line i.v. placement, or biopsy), or anticipation of the need for major surgery during the course of the trial treatment.
6. Concomitant use of oral or i.v. immunosuppressive drugs. Inhaled, topical or intranasal steroids and adrenal replacement steroids \< 10 mg/day (prednisone equivalent) are permitted in the absence of auto-immune disease.
7. Uncontrolled infectious disease, i.e. negative testing for human immunodeficiency virus (HIV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) and syphilis (Treponema Pallidum Hemagglutination Assay \[TPHA\]).
8. (Systemic) autoimmune disease such as, but not limited to, inflammatory bowel disease, multiple sclerosis and lupus. Subjects with type 1 diabetes mellitus, hypothyroidism after autoimmune thyroiditis and skin disorders (eczema and psoriasis) are not excluded.
9. History of clinically significant cardiovascular disease (≤ 6 months prior to Day 1 on trial) such as stroke, Transient Ischemic Attack (TIA), unstable angina, New York Heart Association (NYHA) Grade II or greater congestive heart failure, myocardial infarction, uncontrolled hypertension, cardiac arrhythmia requiring medication, relevant pathological ECG findings or uncontrolled hypertension (systolic \> 150 mm Hg and/or diastolic \> 100 mm Hg).
10. Serious (bleeding and clotting) condition(s) that may interfere with safe administration of PRECIOUS-01.
11. Abnormal or clinically significant coagulation parameters at the discretion of the Clinical Investigator, i.e.:
1. Prothrombin Time - International Normalized Ratio (PT-INR)
2. Activated Partial Thromboplastin Time (APTT)
3. Subjects being treated with anticoagulants are excluded if the coagulation parameters are outside the therapeutic intervals as described in the Summary of Product Characteristics (SmPC) for the administered treatment.
12. Evidence of any other conditions (such as psychological/familial sociological/geographical issues, psychiatric illness, infectious diseases, physical examination or laboratory findings) that may interfere with the planned treatment, affect subject compliance or place the subject at high risk from treatment-related complications. These conditions must be discussed with the subject before registration in the trial.
13. History of severe allergic episodes and/or Quincke's edema.
14. Prior allogeneic tissue/solid organ transplant, stem cell or bone marrow transplant.
15. Known hypersensitivity to any component of PRECIOUS-01.
16. Pregnant or lactating women. A serum pregnancy test should be performed within 7 days prior to start of trial treatment for confirmation in case of childbearing potential.