Prevention of sagopilone-induced neurotoxicity with acetyl-L-carnitine (ALC)
| ISRCTN | ISRCTN75009754 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN75009754 |
| EudraCT/CTIS number | 2008-000879-26 |
| ClinicalTrials.gov number | NCT00751205 |
| Secondary identifying numbers | 311602 |
- Submission date
- 28/11/2008
- Registration date
- 30/01/2009
- Last edited
- 20/05/2019
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Not provided at time of registration
Contact information
Prof Gordon Rustin
Scientific
Scientific
Medical Oncology
The Clock Tower
Mount Vernon Hospital
Northwood
HA6 2RN
United Kingdom
Study information
| Study design | Interventional treatment randomised double-blindparallel assignment phase II safety/efficacy study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Only available to recruiting centres/participants |
| 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 |
| Study acronym | REASON |
| Study objectives | 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(s) | London Research Ethics Committee, 20/10/2008 |
| Health condition(s) or problem(s) studied | 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 | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Sagopilone, Acetyl-L-Carnitine |
| 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 study start date | 29/08/2008 |
| Completion date | 05/08/2010 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 166 globally; 4 in UK |
| Total final enrolment | 271 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 29/08/2008 |
| Date of final enrolment | 05/08/2010 |
Locations
Countries of recruitment
- Belgium
- England
- France
- Germany
- Italy
- Netherlands
- United Kingdom
Study participating centre
Medical Oncology
Northwood
HA6 2RN
United Kingdom
HA6 2RN
United Kingdom
Sponsor information
Bayer Schering Pharma AG (Germany)
Industry
Industry
Müllerstr. 178
Berlin
D-13342
Germany
| Phone | +49 30 468 1111 |
|---|---|
| clinical-trials-contact@bayerhealthcare.com | |
| Website | http://www.bayerhealthcare.com |
"ROR" |
https://ror.org/04hmn8g73 |
Funders
Funder type
Industry
Bayer Schering Pharma AG (Germany)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/04/2013 | 28/02/2019 | Yes | No |
| Basic results | 20/05/2019 | No | No |
Editorial Notes
20/05/2019: The following changes were made to the trial record:
1. Added clinicaltrialsregister.eu link to basic results (scientific).
2. The total final enrollment was added.
28/02/2019: Publication reference added.
02/02/2017: No publications found in PubMed, verifying study status with principal investigator.
