Thaker PH, et al. – Safety and efficacy of escalating doses of weekly GEN–1 with pegylated liposomal doxorubicin (PLD) were evaluated in patients with recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal cancers (EOC). In recurrent or persistent EOC, the combination of GEN–1 with PLD had encouraging clinical benefit and biological activity.

Methods

• Given to the research, patients had persistent or recurrent platinum-resistant EOC.
• In this trial of a standard 3 + 3 phase I dose escalation design, patients receiving intravenous PLD 40 mg/m2(dose level 1 and 2) or 50 mg/m2 (dose level 3) every 28 days and intraperitoneal GEN-1 at 24 mg/m2 (dose level 1) or 36 mg/m2 (dose level 2 and 3) on days 1, 8, 15, and 22 of a 28 day cycle, were incorporated.
• Every 28 days until disease progression, cycles were repeated.
• For toxicity, clinical efficacy, and evidence of systemic and intraperitoneal immunologic effect, patients were monitored.

Results

• A median of 4 cycles (range 1–8) were administered to sixteen evaluable patients.
• Results did not report any dose limiting toxicities.
• 4 grade 3 anemia, 2 grade 3 abdominal pain, 7 grade 3 neutropenia, and 2 grade 4 neutropenia were the adverse side effects.
• In the 14 patients with measurable disease, a clinical benefit of 57.1% (PR = 21.4%; SD = 35.7%) was found.
• Data demonstrated the highest number of partial responses (28.6%) and stable disease (57.1%) at dose level 3.
• In addition, the maximum tolerated dose was not reached.
• In peritoneal fluid following GEN-1 treatment, increases in IL-12, IFN-γ, and TNF-α levels were found.