Study of NGR-hTNF in Combination With Doxorubicin in Patients Affected by Advanced or Metastatic Ovarian Cancer

Study Overview
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Brief Summary
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The main objective of the trial is to document the response rate in patients affected by metastatic ovarian cancer, treated with NGR-hTNF plus doxorubicin. Safety will be established by clinical and laboratory assessment according to NCI-CTC criteria.

Detailed Description
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This is a phase II, open-label,single arm, non-randomized study that will be conducted in patients affected by metastatic ovarian cancer, that will be conducted using Simon's two-stage design method.

Official Title
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NGR012: A Phase II Study of NGR-hTNF Administered in Combination With Doxorubicin Every 3 Weeks in Patients Affected by Advanced or Metastatic Ovarian Cancer

Conditions
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Ovarian Cancer Metastatic Recurrent

Intervention / Treatment
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* Drug: NGR-hTNF
* Drug: doxorubicin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients ≥18 years old affected by advanced or metastatic ovarian cancer previously treated with platinum regimens (cis or carboplatin) plus paclitaxel and with documented progression disease within 6 months from last chemotherapy administered (refractory/resistant population) or in progression disease after 6 months from last chemotherapy (platinum regimens plus paclitaxel) administered Rechallenge with platinum regimens No previous exposure to anthracyclines Histologically or cytologically confirmed ovarian carcinoma Life expectancy more than 3 months ECOG Performance status 0 - 1 Normal cardiac function (LVEF ≥55%) and absence of uncontrolled hypertension Measurable disease defined as ≥1 unidimensional measurable lesion ≥ 20 mm by conventional technics or ≥ 10 mm ( spiral CT scan or PET); ascites is allowed if present with peritoneal carcinosis Adequate baseline bone marrow, hepatic and renal function, defined as follows: Neutrophils > 1.5 x 10^9/L and platelets > 100 x 10^9/L Bilirubin < 1.5 x ULN AST and/or ALT < 2.5 x ULN in absence of liver metastasis AST and/or ALT < 5 x ULN in presence of liver metastasis Serum creatinine < 1.5 x ULN Patients may have had prior therapy providing the following conditions are met: Chemotherapy and radiotherapy: wash-out period of 28 days Surgery: wash-out period of 14 days Absence of any conditions in which hypervolaemia and its consequences (e.g. increased stroke volume, elevated blood pressure) or haemodilution could represent a risk for the patient (take as reference Technical data sheet human albumin specifically used in Pharmacy Department for NGR-hTNF dilution) Patients must give written informed consent to participate in the study Exclusion criteria: Concurrent anticancer therapy Patients must not receive any other investigational agents while on study New York Heart Association class II-IV cardiac disease Acute angina Patients with myocardial infarction within the last six (6) months Patient with significant peripheral vascular disease Thrombosis of main portal vein Clinical signs of CNS involvement 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. Patients with reproductive potential (i.e. menopausal for less than 1-year and not surgically sterilized) must practice effective contraceptive measures throughout the study. Women of childbearing potential must provide a negative pregnancy test (serum or urine) within 14 days prior to registration.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A: NGR-hTNF + doxorubicin<br>NGR-hTNF plus doxorubicin | Drug: NGR-hTNF<br>* NGR-hTNF: 0.8 mcg/m² as 60-minute intravenous infusion every 3 week until confirmed evidence of disease progression or unacceptable toxicity occurs<br>Drug: doxorubicin<br>* Doxorubicin: 60mg/m² every 3 weeks, until cumulative dose of 550 mg/m²<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antitumor activity defined as response rate | Evaluated according to Response evaluation criteria in solid tumors (RECIST) | during the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | PFS evaluated according to Response evaluation criteria in solid tumors (RECIST) | during the study | 
| Overall survival (OS) | Defined as the time from the date of randomization until the date of death due to any cause or the last date the patient was known to be alive | from the date of randomization to the date of death, assessed up to 6 months | 
| CA125 (U/mL) measurement | Tumor marker evaluation | from the randomization, every 6 weeks until the end of treatment | 
| Safety according to NCI-CTCAE criteria (version 3) | To evaluate safety profile related to NGR-hTNF | during the study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NGR-hTNF, Ovarian cancer, Doxorubicin