Condition category
Cancer
Date applied
28/11/2008
Date assigned
30/01/2009
Last edited
01/05/2014
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof Gordon Rustin

ORCID ID

Contact details

Medical Oncology
The Clock Tower
Mount Vernon Hospital
Northwood
HA6 2RN
United Kingdom

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 gave approval on the 20th October 2008.

Study design

Interventional, treatment, randomised, double-blind (subject, investigator, outcomes assessor), parallel 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 measures

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

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
clinical-trials-contact@bayerhealthcare.com

Sponsor type

Industry

Website

http://www.bayerhealthcare.com

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

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes