E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Approximately 75% of women with ovarian cancer present advanced disease. Survival is highly dependent on the stage of disease at the initiation of treatment. Recommended first-line therapy is a combination of platinum drug and paclitaxel. Patients who progress during primary therapy or within 6 months after are considered platinum refractory/resistant. The prognosis of patients with resistant / refractory ovarian cancer is uniformly poor with median overall survival ranging from 35 – 41 weeks |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To show superiority of patupilone in overall survival compared to pegylated liposomal doxorubicin (Doxil®/Caelyx®) in taxane/platinum refractory/resistant patients with recurrent epithelial ovarian, primary fallopian or primary peritoneal cancer. |
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E.2.2 | Secondary objectives of the trial |
•To evaluate progression free survival •To evaluate best overall response rate (RECIST criteria) •To evaluate CA-125 response for patients with evaluable disease as defined by Rustin criteria •To evaluate duration of best overall response •To evaluate time to progression •To evaluate best overall response •To evaluate the safety and tolerability of patupilone administered in this dose, regimen and this pt population •To evaluate detailed cardiac safety surveillance of a single dose of patupilone versus pegylated liposomal doxorubicin on QT interval, heart rate and cardiac conduction intervals in a limited number patients •To conduct PK-PD analysis •To perform pharmacogenomic assessments to examine whether expression levels of beta-tubulin isoforms in tumor cells correlate with resistance to patupilone. •To evaluate patient-reported symptoms and quality of life (QoL) of patients using the FACT-O and EQ-5D. •To evaluate change in disease symptoms, as assessed by the FOSI |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
CARDIAC SAFETY (optional - included in the core protocol and post-text supplement 2) TITLE: A parallel group study in a randomized open label multicenter Phase III trial of Patupilone (EPO906) versus pegylated liposomal doxorubicin (Doxil®/Caelyx®) to evaluate cardiac safety in taxane/platinum refractory/resistant patients with recurrent epithelial ovarian, primary fallopian or primary peritoneal cancer POPULATION: a subgroup of 130 patients patients from each treatment group) who agree to enroll in the sub-study (separate informed consent) OBJECTIVES: · to perform cardiac safety surveillance of the effects of a single dose of patupilone versus a single dose of pegylated liposomal doxorubicin on QT interval (corrected and uncorrected), heart rate (HR), and cardiac conduction intervals (QRS, RR, and PR) in taxane/platinum refractory/resistant patients with recurrent epithelial ovarian, primary fallopian or primary peritoneal cancer.
EXPLORATORY BIOMARKER (optional - included in the core protocol and post-text supplement 6) TITLE: no separate title (included in the core protocol and post-text supplement 6) POPULATION: patients who agree to enroll in this exploratory sub-study (separate informed consent) OBJECTIVES: · To examine whether individual genetic variation in genes relating to drug metabolism, ovarian, primary fallopian, or primary peritoneal cancer, and the drug target pathway confer differential response to Patupilone. · To examine gene expression patterns, proteins, and metabolites of blood and tumor tissue that are associated with treatment response to Patupilone, or that possibly correlate with the severity or progression of ovarian, primary fallopian, or primary peritoneal cancer.
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E.3 | Principal inclusion criteria |
- Histologically confirmed diagnosis of epithelial ovarian, primary fallopian or primary peritoneal cancer. - No more than one prior intravenously administered taxane/platinum-based combination chemotherapy regimen of at least the initial platinum dose of carboplatin AUC 5-6 or cisplatin 75mg/m2 - Taxane/platinum refractory/resistant patients must present with either measurable (by RECIST criteria) or non-measurable (CA-125 by Rustin criteria) progressive disease - Left ventricular ejection fraction (LVEF) >/= 50% by MUGA or 2-D echocardiography - Age > 18 years. - WHO performance status of 0, 1, or 2.
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E.4 | Principal exclusion criteria |
- Patients with CA-125-only disease - Unresolved bowel obstruction - Prior administration of and/or known hypersensitivity to: epothilones, anthracyclines and/or pegylated liposomal doxorubicin - Any peripheral neuropathy > CTC grade 1 - Unresolved diarrhea of any grade within last 7 days prior to start of treatment. - Presenting with leptomeningeal involvement - Within 3 weeks of receiving any prior chemotherapy or radiotherapy or who are planning to receive either while participating in the study - Severe cardiac insufficiency (NYHA III or IV), with uncontrolled and/or unstable cardiac or coronary artery disease - History of another malignancy within 5 years prior to study entry, except curatively treated non-melanotic skin cancer or cervical cancer in situ - Receiving hematopoietic growth factors (except erythropoietin) - Concomitant administration of Coumadin® or other agents containing warfarin - Concomitant administration of any drug/agent known to cause, or increase the severity of, diarrhea Concomitant administration of any drug/agent known to interact negatively with doxorubicin or pegylated liposomal doxorubicin
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of this study is overall survival (OS). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 70 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |