Prevention of Sagopilone-induced Neurotoxicity With Acetyl-L-Carnitine (ALC)

NCT ID: NCT00751205

Last Updated: 2014-10-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-08-31
• Study Completion Date: 2010-08-31

Brief Summary

This study investigates the safety and efficacy of Acetyl-L-Carnitine and compares it to the safety and efficacy of a placebo (inactive) tablet in the prevention of Sagopilone-induced peripheral neuropathy. Patients will receive intravenous infusion of sagopilone for 3 hours on day 1 of a 3-weeks cycle. Treatment with Sagopilone will be given as long as the patient is benefitting. In addition patients will receive ALC or placebo, starting 1 week before first sagopilone infusion and ending 30-33 days after the last infusion with sagopilone. Safety will be determined by laboratory and other evaluations. Efficacy of ALC will be determined by the incidence of all grades of peripheral neuropathy with the results of a patient questionnaire. Efficacy of the combination of ALC and Sagopilone will be determined by the tumor response.

Conditions

Prostate Cancer; Ovarian Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Arm 1

Group Type: EXPERIMENTAL

Sagopilone 16 mg/m^2 i.v., Acetyl-L-Carnitine (ALC) 1000 mg tid, HRPC only: Prednisone or Prednisolone 5 mg bid

Intervention Type: DRUG

Subjects will receive intravenous (i.v.) infusion of Sagopilone for 3 hours on day 1 of a 3-weeks cycle. In addition, subjects will receive Acetyl-L-Carnitine (ALC) 1000 mg tid. Treatment with Sagopilone and ALC will be continued as long as there is benefit. Subjects with HRPC will also receive Prednisone or Prednisolone 5 mg bid, throughout the treatment with Sagopilone.

Arm 2

Group Type: PLACEBO_COMPARATOR

Sagopilone 16 mg/m^2 i.v. and placebo 1000 mg tid, HRPC only: Prednisone or Prednisolone 5 mg bid

Intervention Type: DRUG

Subjects will receive intravenous (i.v.) infusion of Sagopilone for 3 hours on day 1 of a 3-weeks cycle. Treatment will be continued as long as there is benefit. In addition, subjects will receive 21 weeks of placebo 1000 mg tid. After all patients have completed 6 cycles of treatment, an analysis will be performed to see whether ALC was better than placebo. If this is the case, patients still under placebo treatment will be offered to switch to ALC. Subjects with HRPC will also receive Prednisone or Prednisolone 5 mg bid, throughout the treatment with Sagopilone.

Interventions

Sagopilone 16 mg/m^2 i.v., Acetyl-L-Carnitine (ALC) 1000 mg tid, HRPC only: Prednisone or Prednisolone 5 mg bid

Subjects will receive intravenous (i.v.) infusion of Sagopilone for 3 hours on day 1 of a 3-weeks cycle. In addition, subjects will receive Acetyl-L-Carnitine (ALC) 1000 mg tid. Treatment with Sagopilone and ALC will be continued as long as there is benefit. Subjects with HRPC will also receive Prednisone or Prednisolone 5 mg bid, throughout the treatment with Sagopilone.

Intervention Type: DRUG

Sagopilone 16 mg/m^2 i.v. and placebo 1000 mg tid, HRPC only: Prednisone or Prednisolone 5 mg bid

Subjects will receive intravenous (i.v.) infusion of Sagopilone for 3 hours on day 1 of a 3-weeks cycle. Treatment will be continued as long as there is benefit. In addition, subjects will receive 21 weeks of placebo 1000 mg tid. After all patients have completed 6 cycles of treatment, an analysis will be performed to see whether ALC was better than placebo. If this is the case, patients still under placebo treatment will be offered to switch to ALC. Subjects with HRPC will also receive Prednisone or Prednisolone 5 mg bid, throughout the treatment with Sagopilone.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Males or females aged >/= 18 years
• Epithelial ovarian, peritoneal cavity or Fallopian tube cancer (except mucinous or clear cell tumors) or Adenocarcinoma of the prostate
• At least 1 unidimensional 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 (ovarian cancer) or PSA value >/= 5 ng/mL (HRPC).
• Progression of disease (HRPC) despite adequate androgen-inhibiting hormone therapy.
• Progression of disease (Ovarian Cancer) or symptomatic relapse after previous therapy (elevated CA125 levels alone are insufficient for inclusion) WHO performance status 0 to 1
• No clinical residual neuropathy (CTCAE Grade 0 at baseline)
• Adequate recovery from previous surgery, radiation, and chemotherapy (excluding alopecia)
• Adequate function of major organs and systems.
• Survival expectation =3 months
• Histologically or cytologically proven:

1. Epithelial ovarian, peritoneal cavity or Fallopian tube cancer (except mucionous cell tumors or clear cell tumors that have a clear cell component of >33%)

Exclusion Criteria

• Symptomatic brain metastases requiring whole- brain irradiation
• Any concomitant malignancy: the following exceptions are allowed: Non-melanoma skin cancer, Carcinoma in situ of the cervix, Malignancy with definitive treatment >/= 5 years ago without relapse.
• Diabetes mellitus (even if controlled only by special diet)
• History of chronic hepatitis B or C, or known HIV infection
• Seizure disorder requiring medication (such as steroids or anti-epileptics)
• Inability to swallow oral medications
• Prior treatment with epothilones
• Concomitant use of neurotoxic drugs
• Concomitant use of compounds that have potentially positive effects towards symptoms of neuropathy

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bayer Study Director

Role: STUDY_DIRECTOR

Bayer

Locations

Bruxelles - Brussel, , Belgium

Caen, , France

Montpellier, , France

Nantes, , France

Paris, , France

Villejuif, , France

Tübingen, Baden-Wurttemberg, Germany

Rostock, Mecklenburg-Vorpommern, Germany

Bonn, North Rhine-Westphalia, Germany

Essen, North Rhine-Westphalia, Germany

Essen, North Rhine-Westphalia, Germany

Magdeburg, Saxony-Anhalt, Germany

Meldola, Forlì, Italy

Bologna, , Italy

Rimini, , Italy

Roma, , Italy

Amsterdam, , Netherlands

Amsterdam, , Netherlands

Leiden, , Netherlands

Maastricht, , Netherlands

Leicester, Leicestershire, United Kingdom

Northwood, Middlesex, United Kingdom

Countries

Belgium; France; Germany; Italy; Netherlands; United Kingdom

References

Campone M, Berton-Rigaud D, Joly-Lobbedez F, Baurain JF, Rolland F, Stenzl A, Fabbro M, van Dijk M, Pinkert J, Schmelter T, de Bont N, Pautier P. A double-blind, randomized phase II study to evaluate the safety and efficacy of acetyl-L-carnitine in the prevention of sagopilone-induced peripheral neuropathy. Oncologist. 2013;18(11):1190-1. doi: 10.1634/theoncologist.2013-0061. Epub 2013 Oct 8.

Reference Type: DERIVED

PMID: 24105751 (View on PubMed)

Related Links

http://www.clinicaltrialsregister.eu/

Click here to find information about studies related to Bayer Healthcare products conducted in Europe

Other Identifiers

2008-000879-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

91695

Identifier Type: -

Identifier Source: org_study_id