E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
- Advanced refractory or relapsed ovarian cancer - Patients with metastatic hormone-refractory prostate cancer
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066697 |
E.1.2 | Term | Ovarian cancer recurrent |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036909 |
E.1.2 | Term | Prostate cancer metastatic |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary Objective: to demonstrate the superiority of ALC over placebo in the prevention of Sagopilone-induced peripheral neuropathy
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E.2.2 | Secondary objectives of the trial |
Secondary Objectives: • To assess the safety and efficacy of Sagopilone in combination with ALC • To assess the pharmacokinetics of Sagopilone in combination with ALC • To assess the pharmacogenomics of Sagopilone in combination with ALC
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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 |
PK-pharmacokinetic evaluations will be carried out only in selected centers among the patients that take part in the main study. Participation in the sub-study is voluntary. Full title: Pharmacokinetics (optional sub-study) Date, version: 07-Mar-2008, attachment 5 to the main clinical study protocol. Objective: In this parallel group study, the pharmacokinetics of Sagopilone will be investigated following single dose application in order to evaluate the pharmacokinetic behavior of Sagopilone when given alone or in combination with Acetyl-L-Carnitine (ALC). The explanatory results of this research will be reported descriptively without further statistical considerations. Furthermore, baseline ALC concentrations will be monitored in all patients before start of the ALC “loading phase” and during the first and second treatment course before start of the Sagopilone infusion.
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E.3 | Principal inclusion criteria |
All of the following criteria have to be met for inclusion of a patient into the study: 1) Histologically or cytologically proven a) Epithelial ovarian, peritoneal cavity or Fallopian tube cancer (except mucinous cell tumors) or clear cell tumours that have a clear cell component of > 33% or b) Adenocarcinoma of the prostate
Specific for HRPC: 2) At least 1 unidimensionally measurable lesion (suitable for RECIST evaluation) or for patients without measurable disease PSA value ≥ 5 ng/mL 3) Progression of disease despite adequate androgen-inhibiting hormone therapy, demonstrated by: - rising PSA on at least 2 consecutive measurements taken at least 7 days apart. The last measurement must be ≥ 50% greater than the lowest PSA value achieved under the last previous treatment. - PSA at least 4 ng/ml 4) PSA value at screening (4 to 6 weeks after cessation of antiandrogen treatment) must continue to be elevated 5) Serum testosterone < 50 ng/mL (ongoing treatment with luteinizing hormone- releasing hormone (LHRH) analogues or orchiectomy)
Specific for Ovarian cancer 6) At least 1 unidimensionally measurable lesion (suitable for RECIST evaluation) or for patients without measurable disease, CA 125 levels ≥ 2 times the upper limit of normal(ULN) within 3 months and confirmed within 2 weeks prior to first infusion. 7) Progression of disease or symptomatic relapse after previous therapy (elevated CA 125 levels alone are insufficient for inclusion).
General 8) Males or females ≥ 18 years of age 9) WHO performance status 0 to 1 10) No clinical residual neuropathy (CTCAE Grade 0 at baseline) 11) Adequate recovery from previous surgery, radiation, and chemotherapy (excluding alopecia) 12) Adequate function of major organs and systems • Hematopoietic: - Hemoglobin: ≥ 10 g/dL - WBC: ≥ 3,000/mm3 - Absolute neutrophil count: ≥ 1,000/mm3 - Platelet count: ≥ 100,000/mm3 • Hepatic: - Total bilirubin: normal - AST/ALT: ≤ 3 times the upper limit of normal (≤ 5 x upper limit of normal for patients with liver involvement of their cancer) • Renal: - Creatinine: ≤ 2 mg/dL • Cardiovascular: - No symptomatic congestive heart failure - No unstable angina pectoris - No arrhythmia needing continuous treatment - No uncontrolled hypertension - No MI within past 6 months - No cerebrovascular insult within past 6 months • No other uncontrolled concurrent illness 13) Survival expectation ≥3 months 14) Negative pregnancy test at enrollment (females of childbearing potential only) 15) Agreement to use highly effective contraception methods (intra-uterine contraceptive device IUCD, condoms, oral contraceptives, or other adequate barrier contraception) in females of child-bearing potential and adequate barrier birth control measures in men during the course of the trial and two weeks after the completion of the trial. 16) Written informed consent
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E.4 | Principal exclusion criteria |
1) Candidacy for curative resection 2) Symptomatic brain metastases requiring whole-brain irradiation 3) Congenital bleeding diathesis, acquired coagulopathy or patients receiving full dose of anticoagulants for the treatment of thromboembolism 4) Any concomitant malignancy: the following exceptions are allowed: a) Non-melanoma skin cancer b) Carcinoma in situ of the cervix c) Malignancy with definitive treatment ≥ 5 years ago without relapse 5) History of organ allograft 6) Diabetes mellitus (even if controlled only by special diet) 7) History of chronic hepatitis B or C, or known HIV infection 8) Seizure disorder requiring medication (such as steroids or anti- epileptics) 9) Inability to swallow oral medications 10) Any malabsorption condition 11) Active infection 12) Breast feeding 13) Hypersensitivity to the active substance or to any of the excipients of any of the study medications 14) Any condition that in the opinion of the investigator could hamper the compliance with the study protocol.
Excluded therapies and medications, previous and concomitant: 15) Concomitant use of neurotoxic drugs 16) Concomitant use of compounds that have potentially positive effects towards symptoms of neuropathy 17) Time period since prior therapy and start of study treatment: a) Prior radiotherapy: < 4 weeks b) Prior flutamide or cyproterone acetate: < 4 weeks c) Prior bicalutamide or nilutamide: < 6 weeks 18) Anticancer chemotherapy or immunotherapy during the study or within 4 weeks of study entry. Mitomycin C or nitrosureas should not be given within 6 weeks of study entry. 19) Major surgery less than 28 days prior to start of treatment 20) Prior treatment with epothilones 21) Use of any investigational drug within 4 weeks before start of study treatment 22) Alcohol abuse or abuse of other drugs with neurotoxic potential
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall incidence of peripheral neuropathy (any grade) during at most 6 cycles of sagopilone treatment, based on Adverse Events. |
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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 | Yes |
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 | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 32 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
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 | 8 |