Additional identifiers
EudraCT number
2008-000879-26
ClinicalTrials.gov number
NCT00751205
Protocol/serial number
311602
Study information
Scientific title
Double-blind, randomised phase II study to evaluate the safety and efficacy of acetyl-L-carnitine in the prevention of sagopilone-induced peripheral neuropathy
Acronym
REASON
Study hypothesis
Primary objective:
To demonstrate the superiority of acetyl-L-carnitine (ALC) over placebo in the prevention of sagopilone-induced peripheral neuropathy.
Secondary objectives:
1. To assess the safety and efficacy of sagopilone in combination with ALC
2. To assess the pharmacokinetics of sagopilone and ALC in this combination
3. To assess the pharmacogenomics of sagopilone in combination with ALC
Ethics approval
London Research Ethics Committee, 20/10/2008
Study design
Interventional treatment randomised double-blindparallel assignment phase II safety/efficacy study
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Only available to recruiting centres/participants
Condition
Ovarian cancer; hormone-resistant prostate cancer
Intervention
Participants will be enrolled in this study to be randomised (1:1) to one of two parallel treatment arms:
Arm 1: Experimental group -
Subjects will receive intravenous (i.v.) infusion of sagopilone (16 mg/m^2) for 3 hours on day 1 of a 3-week cycle. Duration of treatment is up to 6 courses. In addition, subjects will receive 21 weeks of prophylaxis with Acetyl-L-Carnitine (ALC) 1000 mg three times a day (TID).
Arm 2: Control group -
Subjects will receive i.v. infusion of sagopilone (16 mg/m^2) for 3 hours on day 1 of a 3-week cycle. Duration of treatment is up to 6 courses. In addition, subjects will receive 21 weeks of prophylaxis with placebo TID.
Intervention type
Other
Phase
Phase II
Drug names
Primary outcome measure
Overall incidence of peripheral neuropathy (any grade) during at most 6 cycles of sagopilone treatment, based on adverse events, timeframe based on start of treatment to end of treatment.
Secondary outcome measures
1. Efficacy of ALC:
1.1. Incidence of neuropathy of grade 3 or 4, time to onset of neuropathy, duration of neuropathy, measured from start of treatment to safety follow-up
1.2. Efficacy of ALC: percentage of discontinuations due to neuropathy, measured from start of treatment to safety follow-up
2. Safety of sagopilone in combination with ALC, measured from start of treatment to safety follow-up
3. Efficacy of sagopilone:
3.1. 'Best overall response' according to modified RECIST criteria, measured from start of treatment to end of treatment
3.2. 'Best overall response' according to CA-125 or PSA response, measured from start of treatment to end of treatment
3.3. Time to disease progression, Progression-free survival, measured from start of treatment to progression or death
3.4. Duration of response, measured from start of treatment to progression or death
3.5. WHO performance status, measured from screening to end of treatment
4. Pharmacokinetics:
4.1. Sagopilone concentrations (optional), measured on day 1, 2, 3, 5, 15 of cycle 1 and 2
4.2. ALC concentrations, measured at randomisation, day 1 of cycle 1 and 2
5. Pharmacogenomics (optional): in tumour tissue, blood and ascites, measured from blood sample at screening, tissue sample and ascites whenever available
Overall trial start date
29/08/2008
Overall trial end date
05/08/2010
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Males or females aged 18 years or over
2. World Health Organization (WHO) performance status 0 to 1
3. Epithelial ovarian, peritoneal cavity or fallopian tube cancer (except mucinous or clear cell tumours) or adenocarcinoma of the prostate (hormone-resistant prostate cancer [HRPC])
4. At least one unidimensional measurable lesion (suitable for Response Evaluation Criteria in Solid Tumors [RECIST] evaluation) or for patients without measurable disease, CA 125 levels greater than or equal to two times the upper limit of normal (ULN) within 3 months and confirmed within 2 weeks prior to first infusion (ovarian cancer) or prostate specific antigen (PSA) value greater than or equal to 5 ng/mL (HRPC)
5. For HRPC: progression of disease despite adequate androgen-inhibiting hormone therapy. For ovarian cancer: progression of disease or symptomatic relapse after previous therapy.
6. No clinical residual neuropathy
7. Adequate recovery from previous surgery, radiation, and chemotherapy (excluding alopecia)
8. Adequate function of major organs and systems
9. Survival expectation greater than or equal to 3 months
10. Negative pregnancy test at enrolment (females of childbearing potential only)
11. Written informed consent
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
166 globally; 4 in UK
Participant 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 (some exceptions allowed)
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 human immunodeficiency virus (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
15. Concomitant use of neurotoxic drugs
16. Concomitant use of compounds that have potentially positive effects towards symptoms of neuropathy
17. Prior radiotherapy less than 4 weeks prior
18. Prior flutamide of cyproterone acetate less than 4 weeks prior
19. Prior bicalutamide or nilutamide less than 6 weeks prior
20. Anticancer chemotherapy or immunotherapy during the study or within four weeks of study entry
21. Major surgery less than 28 days prior to start of treatment
22. Prior treatment with epothilones
23. Use of any investigational drug within 4 weeks before start of study treatment
Recruitment start date
29/08/2008
Recruitment end date
05/08/2010
Locations
Countries of recruitment
Belgium, France, Germany, Italy, Netherlands, United Kingdom
Trial participating centre
Medical Oncology
Northwood
HA6 2RN
United Kingdom
Sponsor information
Organisation
Bayer Schering Pharma AG (Germany)
Sponsor details
Müllerstr. 178
Berlin
D-13342
Germany
+49 30 468 1111
clinical-trials-contact@bayerhealthcare.com
Sponsor type
Industry
Website
Funders
Funder type
Industry
Funder name
Bayer Schering Pharma AG (Germany)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list