First-in-human Phase I dose escalation study assessing safety, tolerability and preliminary efficacy of immunomodulatory nanoparticles
- Conditions
- solid tumors10027655
- Registration Number
- NL-OMON52685
- Lead Sponsor
- Tumor Immunology
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 15
1. Age >=18 years at time of signing informed consent.
2. Performance status (ECOG <= 1) (Appendix II).
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. Suitable solid tumor indications include non-small cell lung cancer
(NSCLC), melanoma, epithelial ovarian cancer, bladder cancer, breast cancer,
and synovial sarcoma, adenoid cystic carcinoma, cervical cancer, endometrial
cancer, lung cancer, pancreatic cancer, prostate cancer, myxoid and round cell
liposarcoma, neuroblastoma, vulvar cancer, esophageal cancer, hepatocellular
cancer, and head and neck cancer.
5. Subject with evaluable disease per RECIST v1.1.
6. Adequate hematologic, renal and liver function as defined by laboratory
values performed within 14 days of start of treatment:
a. Hemoglobin (Hb) >= 6 mmol/L;
b. Absolute Lymphocyte Count (ALC) > 0.8 x 109/L;
c. Absolute Neutrophil Count (ANC) >= 1.5 × 109/L;
d. Platelet count > 100 x 109/L;
e. Serum creatinine <= 1.5 x ULN or calculated creatinine clearance >= 60 mL/min
(as determined by MDRD [Modification of Diet in Renal Disease]) for patients
with serum creatinine levels > 1.5 x ULN;
f. Serum bilirubin < 25 µmol/L;
g. Aspartate Aminotransferase (AST), and Alanine Aminotransferase (ALT) <= ULN
unless related to liver metastasis (in which case levels should be < 3 x ULN).
h. Alkaline Phosphatase (ALP) <= ULN unless related to liver or bone marrow
metastases (in which case levels should be <= 3 x ULN).
7. Previous therapy-derived toxicities should be resolved to Grade < 2
according to CTCAE v5.0 (Appendix I), with exceptions for alopecia.
8. 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.
9. 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.
10. Expected adequacy of follow-up.
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 suffering from melanoma, non-Hodgkin lymphoma, or renal cell
carcinoma who have a serum Lactic Acid Dehydrogenase (LDH) > ULN.
5. 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.
6. 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.
7. 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.
8. 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]).
9. (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.
10. 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).
11. Serious (bleeding and clotting) condition(s) that may interfere with safe
administration of PRECIOUS-01.
12. Abnormal or clinically significant coagulation parameters at the discretion
of the Clinical Investigator, i.e.:
a. Prothrombin Time - International Normalized Ratio (PT-INR)
b. Activated Partial Thromboplastin Time (APTT)
c. 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.
13. Evidence of any other conditions (such as psychological/familial
sociological/geographical issues, psychiatric illness, infectious diseases,
physical
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method