Ovarian Cancer
Conditions
Keywords
NGR-hTNF, Pegylated liposomal doxorubicin, Doxorubicin, Platinum-resistant, Progression or recurrence Ovarian Cancer, Ovarian Cancer, Advanced or metastatic
Brief 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
Detailed description
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.
Interventions
DRUGNGR-hTNF
NGR-hTNF: 0.8 mcg/m² as 60 minutes intravenous infusion weekly or every 3 or 4 weeks until confirmed evidence of disease progression or unacceptable toxicity occurs
DRUGPegylated liposomal doxorubicin
50 mg/m² iv every 4 weeks until confirmed evidence of disease progression
DRUGDoxorubicin
60 mg/m² iv every 3 weeks for a maximum of 8 cycles
Sponsors
AGC Biologics S.p.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | from the date of randomization, every 6 and 8 weeks based on type of chemotherapy during treatment and every 12 weeks during the follow-up until PD or death | Defined as the time from the date of randomization until disease progression, or death |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | from the date of randomization, every 6 and 8 weeks based on type of chemotherapy during treatment and every 12 weeks during follow-up until death | defined as the time from the date of randomization until death due to any cause. |
| Response Rate (RR) | from the date of randomization, every 6 and 8 weeks based on type of chemotherapy during treatment and every 12 weeks during the follow-up until PD or death | defined as the percentage of patients who have a best-response rating of complete or partial response, according to standard RECIST criteria. |
| Disease Control Rate (DCR) | from the date of randomization, every 6 and 8 weeks based on type of chemotherapy during treatment and every 12 weeks during the follow-up until PD or death | defined as the percentage of patients who have a best-response rating of complete response, partial response, or stable disease, according to standard RECIST criteria. |
| Duration of Disease Control | from the date of randomization, every 6 and 8 weeks based on type of chemotherapy during treatment and every 12 weeks during the follow-up until PD or death | measured from the date of randomization until disease progression, or death due to any cause. |
| Safety and Toxicity according to NCI-CTCAE criteria (version 4.03) | from the start of treatment until 28 days after last treatment | To evaluate safety and toxicity profile related to NGR-hTNF |
Countries
Italy, United Kingdom
Outcome results
None listed