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 extension protocol is to evaluate the early safety of a new schedule of NGR-hTNF given weekly, instead of every 3 or 4 weeks, in a cohort of 12 patients randomized to the experimental arm A, as compared to a reference cohort of 12 patients randomized to an anthracycline alone
Detailed description
In this extension protocol IPR/26 of completed IPR/24 study, considering the relatively short half-life of approximately 1 hour and the favourable toxicity profile of NGR-hTNF, characterized by transient constitutional symptoms occurring during the first day of administration, an additional cohort of 24 patients will be randomized and the 12 patients enrolled in arm A will receive the same dose of NGR-hTNF 0.8 mcg/m2 given as 60 minutes infusion every week. the weekly schedule of NGR-hTNF 0.8 mcg/m2 has previously been tested in several studies
Interventions
DRUGNGR-hTNF
NGR-hTNF: 0.8 mcg/m² as 60 minutes intravenous infusion every week 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 and absence of uncontrolled hypertension * 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: 1. Surgery and radiation therapy: wash-out period of 14 days 2. 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 or contraindications 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 |
|---|---|---|
| Safety according to NCI-CTCAE criteria (version 4.03) | from the start of treatment until 28 days after last treatment | To evaluate safety profile related to NGR-hTNF |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | from randomization date, every 6-8 weeks based on chemotherapy during treatment and every 12 weeks during follow-up until first documented PD or death from any cause, whichever came first, assessed up through study completion, approximately 12 months | Defined as the time from the date of randomization until disease progression, or death |
| Overall survival (OS) | from randomization date, every 6-8 weeks based on type of chemotherapy during treatment and every 12 weeks during follow-up until date of death, from any cause, assessed up through study completion, approximately 12 months | defined as the time from the date of randomization until death due to any cause |
| Response Rate (RR) | from randomization date, every 6-8 weeks based on chemotherapy during treatment and every 12 weeks during follow-up until first documented PD or death from any cause, whichever came first, assessed up through study completion, approximately 12 months | 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 randomization date, every 6-8 weeks based on chemotherapy during treatment and every 12 weeks during follow-up until first documented PD or death from any cause, whichever came first, assessed up through study completion, approximately 12 months | 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 randomization date, every 6-8 weeks based on chemotherapy during treatment and every 12 weeks during follow-up until first documented PD or death from any cause, whichever came first, assessed up through study completion, approximately 12 months | measured from the date of randomization until disease progression, or death due to any cause |
Countries
Italy
Outcome results
None listed