This is a Phase 1b, open-label, dose-escalation clinical study evaluating the safety of camsirubicin with prophylactic pegfilgrastim in the treatment of advanced soft tissue sarcomas. Following a screening period of up to 28 days, eligible patients will receive camsirubicin through intravenous (IV) infusion (8 mL/min rate) once every 21 days, starting on Day 1 of a 21-day cycle for 6 cycles. Dose will be based on the patient's body surface area (BSA). Patients who demonstrate clinical benefit (defined as stable disease or better) at the completion of 6 cycles will be allowed to continue to receive camsirubicin until disease progression or unacceptable toxicity. All patients receiving camsirubicin will also receive 6 mg of prophylactic pegfilgrastim approximately 24-96 hours after each camsirubicin infusion to prevent neutropenia. The dose escalation will start at 265 mg/m2, with dose increments for subsequent dose groups of 50% until a drug-related Grade 2 non-hematologic toxicity is observed, at which point subsequent dose escalations will be in increments of 25% until an MTD is identified.
At each successive dose level, cohorts of 3 new patients will be entered if no dose-limiting toxicity (DLT) is observed (3+3 design) within 21 days of initial dose. If a patient treated at any dose level experiences a DLT, a total of up to 6 patients will be treated at that dose level. Once two patients at any dose level experience a DLT, no additional patients will be treated at that level. The MTD is defined as the highest dose level below the dose level at which 2 or more patients experience a DLT during the first 21 days from Cycle 1 Day 1. This will be the RP2D unless safety concerns suggest a lower dose. Patients in each new cohort at all dose levels (i.e., all patients receiving their initial dose of camsirubicin at the designated dose level) will successfully complete one cycle of treatment prior to beginning treatment of the new cohort of patients at the next higher dose level.
The RP2D dose may be expanded by 6 patients to obtain additional PK and safety data at this dose. Patients will be followed for adverse events of special interest (AESI), which include the incidence of congestive heart failure (CHF) and left ventricular ejection fraction (LVEF) dysfunction. Patients will be followed for 1 year post last dose and AESI assessed every 3 months. Assessments will include LVEF assessment by echocardiogram or multi-gated radionuclide angiography (MUGA) scan and measurement of Troponin-I. LVEF assessments should be collected even if the patient will go on to other anticancer therapies during the 1-year post last dose long-term follow-up period. If cardiac toxicity is suspected, an echocardiogram should be performed sooner if a patient develops signs and symptoms of congestive heart failure (e.g., shortness of breath during mild exertion or when lying down, feel very tired, cough (especially at night), swelling of the feet and/or ankles).
Patients with serious adverse events (SAEs) or AESI assessed by the investigator during the 1-year follow-up period as related to study medications will be followed until the AE completely resolves or is assessed as chronic. Unresolved SAE or AESI at the end of the 1-year long-term follow-up period will be followed for status for up to 2 years at approximately 3-month intervals.
