This is a Phase 1b, open-label, non-randomized, Dose Confirmation study. Subjects will be treated, once a week, with IV doses of Nerofe and low dose (20 mg/m2) Doxorubicin (6-8 hours from one another) in consecutive, 28-day cycles.
Subjects will be evaluated regularly for safety. Subjects will return for a follow-up visit 30-33 days after the last dosing of study drug. Subjects who tolerate the drug and who do not experience progressive disease, intolerable toxicity, or meet any of the other withdrawal criteria - may continue to receive Nerofe \& Doxorubicin for up to 5 cycles, at the discretion of the Principal Investigator. Throughout the trial, oversight will be provided by the Clinical Safety Committee (CSC).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Once weekly treatment, with IV doses of Nerofe (96mg\\m2) and low dose (20 mg/m2) Doxorubicin 5 or 24 hours from one another) .
Oncologic Institue, Kaplan
Rehovot, Israel
The primary safety endpoint will be the Adverse Events (AE) reported during the combined treatment of Nerofe and low Dose doxorubicin , using the CTCAE score.
The Adverse Events (AE) reported during the combined treatment of Nerofe and low Dose doxorubicin, using the CTCAE score.
Time frame: Safety data will be collected weekly during the subjects visits(Weeks 1-20), throughout the study and up to 1 year.
Assessing Change in tumor size from Baseline to End of study
Assessing Change in tumor size from Baseline to End of study under combined treatment of Nerofe and Low dose Doxorubicin in Ovarian cancer or triple negative breast cancer. Subject population will be evaluated using Response Evaluation Criteria in Solid Tumors, from Baseline, and every 2 cycles( 8 weeks), and last one- at the end of the study.
Time frame: Imaging would be performed at Baseline and at the end of every 2 cycles(8 weeks), through the study completion, which is estimated to be after 6 months.
Assessing Change in Blood markers from Baseline to End of study
Assessing Change in tumor size from Baseline to End of study, under combined treatment of Nerofe and Low dose Doxorubicin, in Ovarian cancer or triple negative breast cancer. Subject population will be evaluated from Baseline, and every cycle( 28 days each cycle) until the end of the study.
Time frame: Blood Markers would be measured at Baseline, and at the end of every cycle(28 Days in each cycle), through the study completion, which is estimated to be after 6 months.
Pharmacokinetic Profile
Pharmacokinetic Profile, including area under the curve.
Time frame: Pharmacokinetic sampling is planned once at Baseline. In Cycle 1(28 Days in each cycle), and Cycle 2 Day 1 visits: pre-dose and following the end of Nerofe infusion: 15 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, and 24 hours
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Pharmacokinetic Profile
Pharmacokinetic Profile, including maximum plasma concentration
Time frame: Pharmacokinetic sampling is planned once at Baseline. In Cycle 1(28 Days in each cycle), and Cycle 2 Day 1 visits: pre-dose and following the end of Nerofe infusion: 15 min ,1 hour, 2 hours, 4 hours, 6 hours, 8 hours, and 24 hours.
Pharmacokinetic Profile
Pharmacokinetic Profile, including trough plasma concentration.
Time frame: Pharmacokinetic sampling is planned once at Baseline. In Cycle 1(28 Days in each cycle), and Cycle 2 Day 1 visits: pre-dose and following the end of Nerofe infusion: 15 min, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, and 24 hours.
Pharmacokinetic Profile
Pharmacokinetic Profile, including time to maximum plasma concentration.
Time frame: Pharmacokinetic sampling is planned once at Baseline. In Cycle 1(28 Days in each cycle), and Cycle 2 Day 1 visits: pre-dose and following the end of Nerofe infusion: 15 min, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, and 24 hours.
Pharmacokinetic Profile
Pharmacokinetic Profile, including plasma half-life.
Time frame: Pharmacokinetic sampling is planned once at Baseline. In Cycle 1(28 Days in each cycle), and Cycle 2 Day 1 visits: pre-dose and following the end of Nerofe infusion: 15 min, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, and 24 hours.
Pharmacodynamics profile
PharmacoDynamics profile, including changes in plasma levels of circulating cytokines
Time frame: PharmacoDynamics sampling is planned at Baseline, at Day 1, 15, visits of every cycle (28 Days in each cycle), through the study completion which is estimated to be after 6 months..
Pharmacodynamics profile
PharmacoDynamics profile, including changes in plasma levels of soluble T1/ST2 receptor
Time frame: PharmacoDynamics sampling is planned at Baseline, at Day 1, 15, visits of every cycle (28 Days in each cycle), through the study completion which is estimated to be after 6 months.
Pharmacodynamics profile
PharmacoDynamics profile, including changes in Peripheral blood mononuclear cells' T1/ST2 receptor expression
Time frame: PharmacoDynamics sampling is planned at Baseline, at Day 1, 15, visits of every cycle (28 Days in each cycle), through the study completion which is estimated to be after 6 months.
Pharmacodynamics profile
Immunogenicity of Nerofe, through the analysis of Plasma levels of circulating anti-Nerofe antibodies.
Time frame: PharmacoDynamics sampling is planned at Baseline, at Day 1, 15, visits of every cycle(28 Days in each cycle), through the study completion which is estimated to be after 6 months.