phase ii study of ngr-htnf in combination with doxorubicin in platinum-resistant ovarian cancer

Conditions: Ovarian Cancer

Summary: the primary objective of this randomized phase ii trial is to compare progression-free survival (pfs) in patients randomized to ngr-htnf plus an anthracycline versus patients randomized to an anthracycline alone

considering the safety/toxicity profile of ngr-htnf characterized by mild-to-moderate constitutional symptoms, the reversibility of these adverse events generally occurring only during the infusion time; the absence of overlapping toxicities with chemotherapeutic agents; the safety and preliminary antitumor activity observed in previous trial with doxorubicin; and the objective response rate (rr) registered in a phase ii trial in previously treated ovarian cancer patients seems justified to evaluate in a randomized phase ii trial the efficacy of ngr-htnf against a doxorubicin-based option in advanced ovarian cancer patients progressing or recurrent after a standard platinum/taxane-based chemotherapy.

Eligibility criteria:
inclusion criteria: * age ≥ 18 years * histologically-proven ovarian cancer, fallopian tube and primary peritoneal cancer in advanced or metastatic stage * patients previously treated with a maximum of two platinum-based regimen plus paclitaxel and with documented progressive disease on treatment (refractory patient population) or within 6 months from last chemotherapy cycle (resistant patient population) * ecog performance status 0 - 2 * life expectancy of 12 weeks or more * normal cardiac function * adequate baseline bone marrow, hepatic and renal function defined as follows: 1. neutrophils ≥ 1.5 x 109/l; platelets ≥ 100 x 109/l; hemoglobin ≥ 9 g/dl 2. bilirubin ≤ 1.5 x uln 3. ast and/or alt ≤ 2.5 x uln in absence of liver metastasis or ≤ 5 x uln in presence of liver metastasis 4. serum creatinine \< 1.5 x uln * at least one (not previously irradiated) target lesion or non-measurable disease only, according to recist criteria * patients may have had prior therapy providing the following conditions are met: * surgery and radiation therapy: wash-out period of 14 days * systemic anti-tumor therapy: wash-out period of 21 days * patients must give written informed consent to participate in the study exclusion criteria: * patients must not receive any other investigational agents while on study * more than two previous chemotherapy lines and previous treatment with anthracycline * patients with myocardial infarction within the last six months, unstable angina, new york heart association (nyha) grade ii or greater congestive heart failure, or serious cardiac arrhythmia requiring medication * prolonged qtc interval (congenital or acquired) \> 450 ms * history or evidence upon physical examination of cns disease unless adequately treated * patients with active or uncontrolled systemic disease/infections or with serious illness or medical conditions, which is incompatible with the protocol * known hypersensitivity/allergic reaction to human albumin preparations or to any of the excipients * any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol * pregnancy or lactation.

Keywords: ngr-htnf pegylated liposomal doxorubicin doxorubicin platinum-resistant progression or recurrence ovarian cancer ovarian cancer advanced or metastatic