solid tumors, brain metastases solide tumoren, hersenmetastasen Recurrent Malignant Glioma
Conditions
Interventions
The study will be conducted in 2 stages: A Dose-Escalation Phase and an Expansion Phase.
In the Dose-Escalation Phase, female and male patients with solid tumors and brain metastases or recurrent ma
Sponsors
to-BBB Technologies B.V.
to-BBB technologies BV
Niels Bohrweg 11, 2333 CA Leiden
Bio Partner Center II
The Netherlands
Phone: +31 (0) 71 3322256
Fax: +31 (0) 84 8313409
Email: gladdines@tobbb.com
Eligibility
Inclusion criteria
Inclusion criteria: 1. Age at least 18 years; 2. Measurable or evaluable brain disease; 3. ECOG Performance Status ≤ 2; 4. Estimated life expectancy of at least 8 weeks; 5. Toxicities incurred as a result of previous anticancer therapy (radiation therapy, chemotherapy, or surgery) must be resolved to ≤ grade 2 (as defined by CTCAE version 4.0); 6. No evidence of (cortical) cognitive impairment as defined by a Mini-Mental Status Exam (MMSE) score ≥ 25/30; 7. No evidence of sub cortical cognitive impairment as defined by a score on HIV Dementia Scale (HDS) > 10; 8. Written informed consent according to local guidelines. In addition to the above listed eligibility criteria, the following criteria are applicable: 9. Dose-Escalation Phase: Female and male patients with pathologically confirmed diagnosis of advanced, recurrent solid tumors and unequivocal evidence of brain metastases that are refractory to standard therapy or for which no standard therapy exists. Brain metastases may be stable, progressive, symptomatic or asymptomatic brain metastasis/es. Stable or decreasing dosage of steroids (e.g. dexamethason) for 7 days prior to baseline MRI or non-enzyme inducing anti-epileptic drugs is allowed OR; Female and male patients with pathology confirmed diagnosis of advanced, recurrent primary malignant (grade III and IV) glioma that are refractory to standard therapy or for which no standard therapy exists. Stable or decreasing dosage of steroids (e.g. dexamethason) for 7 days prior to baseline MRI or non-enzyme inducing anti-epileptic drugs are allowed; 10. Expansion Phase: Female patients with pathologically confirmed diagnosis of advanced, recurrent breast cancer with unequivocal evidence of brain metastases that are refractory to standard therapy or for which no standard therapy exist. Brain metastases may be stable, progressive, symptomatic or asymptomatic brain metastasis/es. Stable or decreasing dosage of steroids (e.g. dexamethason) for 7 days prior to baseline MRI or non-enzyme inducing anti-epileptic drugs is allowed.
Exclusion criteria
Exclusion criteria: Prior Treatment: 1. Less than 4 weeks since the last treatment of chemotherapy, biological therapy, immunotherapy and systemic radiotherapy (except palliative radiation delivered to 360mg/m2 for doxorubicin or > 600mg/m2 for epirubicin. Current Treatment: 3. Current or recent (within 30 days of first study treatment) treatment with another investigational drug or participation in another investigational study. Hematology, coagulation and biochemistry: 4. Inadequate bone marrow function: Absolute Neutrophil Count (ANC): 1.5 x the ULN for the institution if no liver metastases (> 2 x ULN in patients with liver metastases); B. ASAT or ALAT > 2.5 x ULN if no liver metastases (> 4 x ULN in patients with liver metastases); C. Alkaline phosphatase levels > 2.5 x ULN if no liver metastases (> 5 x ULN in patients with liver metastases, or > 10 x ULN in patients with bone metastases). 6. Inadequate renal function, defined as: A. Serum creatinine > 1.5 x ULN. Other: 7. Clinical suspicion or radiological evidence of leptomeningeal metastases; 8. Pregnancy or lactation. Serum pregnancy test to be performed within 7 days prior to study treatment start, or within 14 days followed by a confirmatory urine pregnancy test within 7 days prior to study treatment start; 9. For female subjects of childbearing potential (defined as 150 mm Hg and/or diastolic > 100mm Hg); 13. Clinically significant (i.e. active) cardiovascular disease defined as: A. Stroke within ≤ 6 months prior to day 1; B. Transient Ischemic Attack (TIA) within ≤ 6 months prior to day 1; C. Myocardial infarction within ≤ 6 months prior to day 1; D. Unstable angina; E. New York Heart Association (NYHA) Grade II or greater Congestive Heart Failure (CHF); F. Serious cardiac arrhythmia requiring medication; G. Clinically relevant pathologic findings in ECG. 14. Left Ventricle Ejection Fraction (LVEF) by MUGA or ECHO < 50%; 15. Known hypersensitivity to any of the study drug components or excipients (e.g. doxorubicin, PEG or GSH); 16. Evidence of any other medical conditions (such as psychiatric illness, infectious diseases, physical examination or laboratory findings) that may interfere with the planned treatment, affect patient compliance or place the patient at high ri
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To assess the safety and tolerability of 2B3-101 in patients with solid tumors and brain metastases or recurrent malignant glioma, in order to determine the Maximum Tolerated Dose (MTD). | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. To examine the pharmacokinetics (PK) in plasma of 2B3-101 in terms of Cmax, Vss, T1/2, AUC, CL; 2. To obtain preliminary information on the clinical anti-tumor activity of 2B3-101 in terms of objective response rate and duration of response. | — |
Contacts
Public ContactDieta Brandsma
Antoni van Leeuwenhoek Ziekenhuis
Outcome results
None listed