Addition of vandetanib to standard therapy (pegliposomal doxorubicin) in patients with recurrent ovarian cancer. A multi-centre, non-randomized, open phase I/randomized phase II study - AGO-OVAR 2.13

• Conditions: Ovarian Cancer; MedDRA version: 9.1Level: LLTClassification code 10033128Term: Ovarian cancer

• Registration Number: EUCTR2008-005557-38-DE
• Lead Sponsor: AstraZeneca GmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-12-11
• Last Update Posted: 3 June 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: Not specified

Inclusion Criteria

For inclusion in the study subjects must fulfil all of the following criteria.
1.Provision of informed consent prior to any study specific procedures
2.Female aged 18 years and over
3.Histopathologically documented invasive epithelial ovarian carcinoma, cancer of the fallopian tube or the peritoneum refractory to platinum-based chemotherapy or with partially platinum sensitive disease. Platinum-refractory or partially platinum-sensitive patients are defined as those who progressed on or did not respond to first-line platinum-based chemotherapy or who progressed on or did not respond to second-line platinum-based chemotherapy within 12 months after end of therapy. A progression-free-interval of 12 months is defined as time from application of last platinum based chemotherapy + cycle length until first evidence of disease progression.
4.Planned therapy with pegylated liposomal doxorubicin 50 mg/m² for recurrent platinum-refractory ovarian cancer.
5.Patients with a progression-free-interval of 6 to 12 months after platinum-based chemotherapy are only eligible if a further course of platinum-based combination chemotherapy is not possible as judged by the investigator(s).
6.Patients must have received at least one previous platinum- and taxane-based chemotherapy regimen.
7.Measurable disease according to RECIST criteria or alternatively evaluable disease according to RECIST criteria in combination with CA 125 GCIG criteria (see Appendix I)
8.Life expectancy of 12 weeks or longer
9.Performance status ECOG 0-2 (see Appendix H)
10.Adequate organ function defined as: Leukocytes >3,000/µl, absolute neutrophil count >1,500/µl, platelets >100,000/µl, hemoglobin >10 g/dl, total bilirubin <1,5 x ULRR, AST (SGOT) and ALT (SGPT) <2,5 x ULRR, creatinine <1,5 ULRR or creatinine clearance >50 mL/min (calculated by Cockcroft-Gault-Formula, see Appendix G)
11.Able to swallow study medication
12.Negative pregnancy test for female subjects of childbearing potential

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Subjects must not enter the study if any of the following exclusion criteria are fulfilled
1.Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
2.Previous randomization of treatment in the present study
3.Participation in a clinical study and/or receipt of an investigational drug during the last 30 days (participation in the survival follow-up period of a study is not an exclusion)
4.Brain metastases or spinal cord compression, unless treated at least 4 weeks before first dose and stable without steroid treatment for 10 days
5.Any concomitant medications that may cause QTc prolongation or induce Torsades de Pointes (see Appendix C for the lists of medications in Table 1 and Table 2) or induce CYP3A4 function (see Appendix E and Section 6.5). Drugs listed in Appendix C, Table 2, that in the investigator’s opinion cannot be discontinued, are allowed, but only of the QTc is <460 msec.
6.Major surgery within 4 weeks before randomization, any planned surgery or any incompletely healed surgical incision.
7.Any serious non-healing wounds, acute or non-healing ulcers, or bone fractions in the last three months
8.Treatment with mouse-antibodies in patients with evaluable disease and CA-125 progressive disease in the last 3 months. These patients are only eligible in case of measurable disease according to RECIST or cytological/histological proven relapse
9.More than two prior lines of chemotherapy
10.Any chemotherapy or other systemic anti-cancer therapy within four weeks prior to randomization.
11.Radiation therapy within the last 4 weeks prior to randomization (with the exception of palliative radiotherapy)
12.Potassium <4.0 mmol/L despite supplementation, or above the CTCAE grade 1 upper limit.
13.Calcium or Magnesium below LLRR.
14.Significant cardiac event (eg myocardial infarction), superior vena cava [SVC] syndrome, New York Heart Association [NYHA] classification of heart disease =2 (see Appendix D), within 12 weeks before randomization, or presence of cardiac disease that in the opinion of the investigator increases the risk of ventricular arrhythmia
15.History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment (CTCAE grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Subjects with atrial fibrillation controlled by medication are permitted.
16.Congenital long QT syndrome or 1st degree relative with unexplained sudden death under 40 years of age
17.QT prolongation with other medications that required discontinuation of that medication
18.Presence of left bundle branch block (LBBB)
19.QTc with Bazett’s correction unmeasurable or =480 msec or greater on screening ECG (see Figure 2) (Note: If a subject has QTc interval =480 msec on screening ECG, the screening ECG may be repeated 2 times [at least 24 hours apart] for a total of 3 ECG’s. The average QTc from the three screening ECG’s must be <480 msec in order for the subject to be eligible for the study.) If a subject is receiving one of the medications that has a risk of QTc prolongation but that has not clearly been associated with possible association with Torsades de Pointes (see Appendix C, Table 2) prior to study entry, and it cannot be discontinued before study treatment, then the screening QTc must be <460 mse

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified