Addition of Vandetanib to Standard Therapy Pegliposomal Doxorubicin (PLD)

Study Overview
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Brief Summary
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This multi-centre, non-randomized open phase I/randomized phase II study will be conducted in 70 patients (10 in phase I, 60 in phase II) with platinum-refractory recurrent epithelial cancer of the ovary, fallopian tube or peritoneum. A total of approximately 5 national centers will participate in phase I of the study. If the starting criteria for phase II of the study are met at the end of phase I, a total of approximately 20 national centers will participate in phase II of the study.

Official Title
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Addition of Vandetanib to Standard Therapy (Pegliposomal Doxorubicin) in Patients With Recurrent Ovarian Cancer. A Multicentre Phase I / Randomized Phase II Study

Conditions
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Ovarian Cancer

Intervention / Treatment
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* Drug: Vandetanib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Planned therapy with pegylated liposomal doxorubicin 50 mg/m² for recurrent platinum-refractory ovarian cancer. 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). Patients must have received at least one previous platinum- and taxane-based chemotherapy regimen. Exclusion Criteria: Brain metastases or spinal cord compression, unless treated at least 4 weeks before first dose and stable without steroid treatment for 10 days Any concomitant medications that may cause QTc prolongation or induce Torsades de Pointes or induce CYP3A4 function 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 More than two prior lines of chemotherapy. Any chemotherapy or other systemic anti-cancer therapy within four weeks prior to randomization. Radiation therapy within the last 4 weeks prior to randomization (with the exception of palliative radiotherapy

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: 1<br>Vandetanib added to standard therapy (pegliposomal doxorubicin) | Drug: Vandetanib<br>* 100mg doses orally, once daily<br>* Other names: Zactima;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Description (on the Basis of the Safety Set): Safety and Tolerability by Means of the Incidence and Type of Adverse Events (AEs). | Number of participants with at least 1 adverse event of grade 3 or higher (CTCAE grade 3=severe, CTCAE grade 4=life threatening/disabling, CTCAE grade 5=death, as defined by National Cancer Institute CTCAE, Version 3) | From date of registration (Informed Consent Form completed) to date of last vist, up to 18 months. | 
| Description (on the Basis of the Safety Set): Safety and Tolerability by Means of Clinically Significant Laboratory Abnormalities. | Number of patients with elevated liver enzymes grade 3 (CTCAE grade 3=severe, CTCAE grade 4=life threatening). | From date of registration (Informed Consent Form completed) to date of last vist, up to 18 months. | 
| Description (on the Basis of the Safety Set): Safety and Tolerability by Means of the Incidence and Type of Adverse Events (AEs). Number of Participants With Dermatologic Skin Reactions Grade 3/4. | Number of participants with dermatologic skin reactions grade 3/4 (CTCAE grade 3= severe, CTCAE grade 4=life threatening) | From date of registration (Informed Consent Form completed) to date of last vist, up to 18 months. | 
| Description (on the Basis of the Safety Set): Safety and Tolerability by Means of the Incidence and Type of Adverse Events (AEs). Number of Participants With Palmar-plantar Erythrodysesthesia (PPE) Grade 3/4. | Number of participants with palmar-plantar erythrodysesthesia (PPE) grade 3/4 (CTCAE grade 3=severe skin changes with pain, CTCAE grade 4=life threatening). | From date of registration (Informed Consent Form completed) to date of last vist, up to 18 months. | 
| Description (on the Basis of the Safety Set): Safety and Tolerability by Means of the Incidence and Type of Adverse Events (AEs). Number of Participants With Mucositis Grade 3. | Number of participants with mucositis grade 3 (CTCAE grade 3=severe pain interfering with oral intake) | From date of registration (Informed Consent Form completed) to date of last vist, up to 18 months. | 
| Description (on the Basis of the Safety Set): Safety and Tolerability by Means of Clinically Significant Laboratory Abnormalities. Number of Participants With Neutropenia Grade 3/4. | Number of participants with neutropenia grade 3/4 (CTCAE grade 3=severe, CTCAE grade 4=life threatening). | From date of registration (Informed Consent Form completed) to date of last vist, up to 18 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation (for ITT Set): Clinical Activity of Once Daily Oral Vandetanib 100 mg When Added to Standard Therapy (See Above), by Assessment of Progression Free Survival (PFS). | Progression Free Survival: Progression is defined using RECIST, as a measurable increase of at least 20% in the sum of longest diameters of target lesions or unequivocal progression of non-target lesions, or the appearance of new lesions, since baseline. | From date of registration (Informed Consent Form completed) until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 months. | 
| Evaluation (for ITT Set): Clinical Activity of Once Daily Oral Vandetanib 100 mg When Added to Standard Therapy (See Above), by Assessment of Overall Survival (OS). | Median overall survival (OS) | From date of registration (Informed Consent Form completed) until the date of death. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ZD6474, Vandetanib, Zactima, Ovarian Cancer, Phase I, Phase II, Randomized, Safety