Prevention of Sagopilone-Induced Neurotoxicity With Acetyl-L-Carnitine (ALC) - Full Text View

Sponsored by:	Bayer
Information provided by:	Bayer
ClinicalTrials.gov Identifier:	NCT00751205

Purpose

This study investigates the safety and efficacy of Acetyl-L-Carnitine and compares it to the safety and efficacy of 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. Up to 6 courses of treatment with Sagopilone will be given. In addition patients will receive ALC or placebo, starting 1 week before first sagopilone infusion and ending 30 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 and with the results of a patient questionnaire. Efficacy of the combination of ALC and Sagopilone will be determined by the tumor response.

Condition	Intervention	Phase
Prostate Cancer Ovarian Cancer	Drug: Sagopilone 16 mg/m2 i.v. and Acetyl-L-Carnitine (ALC) Placebo tid Drug: Sagopilone 16 mg/m2 i.v. and Placebo tid	Phase II

MedlinePlus related topics: Cancer Ovarian Cancer Peripheral Nerve Disorders Prostate Cancer

Drug Information available for: Prednisolone 6-Methylprednisolone Depo-medrol Medrol veriderm Methylprednisolone Methylprednisolone hemisuccinate Methylprednisolone Sodium Succinate Prednisolone acetate Prednisolone sodium phosphate Prednisolone Sodium Succinate Prednisone Carnitine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Parallel Assignment, Safety/Efficacy Study
Official Title:	(REASON) Double-Blind, Randomized Phase II Study to Evaluate the Safety and Efficacy of Acetyl-l-Carnitine in the Prevention of Sagopilone-Induced Peripheral Neuropathy.

Further study details as provided by Bayer:

Primary Outcome Measures:

Overall incidence of peripheral neuropathy (any grade) during at most 6 cycles of Sagopilone treatment, based on the Adverse Events. [ Time Frame: Based on start of treatment to end of treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Efficacy of ALC: incidence of neuropathy of grade 3 or 4, time to onset of neuropathy, duration of neuropathy. [ Time Frame: Start of treatment to safety Follow-up ] [ Designated as safety issue: Yes ]
Efficacy of ALC: Percentage of discontinuations due to neuropathy. [ Time Frame: Start of treatment to safety Follow-up ] [ Designated as safety issue: No ]
Safety of Sagopilone in combination with ALC. [ Time Frame: Baseline to Safety follow-up ] [ Designated as safety issue: Yes ]
Efficacy of Sagopilone: 'best overall response' according to modRECIST criteria [ Time Frame: Start treatment to End of Treatment ] [ Designated as safety issue: No ]
Efficacy of Sagopilone: 'best overall response' according to CA-125 or PSA response [ Time Frame: Start treatment to End of Treatment ] [ Designated as safety issue: No ]
Efficacy of Sagopilone: Time to disease progression, Progression-free survival [ Time Frame: Start treatment to Progression or Death ] [ Designated as safety issue: No ]
Efficacy of Sagopilone: Duration of response [ Time Frame: Start treatment to Progression or Death ] [ Designated as safety issue: No ]
Efficacy of Sagopilone: WHO performance status. [ Time Frame: Screening to end of Treatment ] [ Designated as safety issue: No ]
Pharmacokinetic: Sagopilone concentrations (optional) [ Time Frame: Day 1,2,3,5,15 of cycle 1 and day2 ] [ Designated as safety issue: No ]
Pharmacokinetic: ALC concentrations [ Time Frame: radomisation, day 1 of cycle 1 and 2 ] [ Designated as safety issue: No ]
Pharmacogenomics (optional): in tumor tissue, blood and ascites [ Time Frame: Blood sample at screening, tissue sample and ascites whenever available ] [ Designated as safety issue: No ]

Estimated Enrollment:	140
Study Start Date:	August 2008
Estimated Study Completion Date:	December 2010
Estimated Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm 1: Experimental	Drug: Sagopilone 16 mg/m2 i.v. and Acetyl-L-Carnitine (ALC) Placebo tid Subjects will receive intravenous (i.v.) infusion of Sagopilone for 3 hours on day 1 of a 3-weeks cycle. Duration of treatment is up to 6 courses. In addition, subjects will receive 21 weeks ofAcetyl-L-Carnitine ( ALC) 1000mg tid. Subjects with HRPC will also receive Prednisone or Prednisolone 5mg bid, throughout the treatment with Sagopilone.
Arm 2: Placebo Comparator	Drug: Sagopilone 16 mg/m2 i.v. and Placebo tid Subjects will receive intravenous (i.v.) infusion of Sagopilone for 3 hours on day 1 of a 3-weeks cycle. Duration of treatment is up to 6 courses. In addition, subjects will receive 21 weeks ofAcetyl-L-Carnitine (ALC) 1000mg tid. Subjects with HRPC will also receive Prednisone or Prednisolone 5mg bid, throughout the treatment with Sagopilone.

Arms

Assigned Interventions

Arm 1: Experimental

Drug: Sagopilone 16 mg/m2 i.v. and Acetyl-L-Carnitine (ALC) Placebo tid

Subjects will receive intravenous (i.v.) infusion of Sagopilone for 3 hours on day 1 of a 3-weeks cycle. Duration of treatment is up to 6 courses. In addition, subjects will receive 21 weeks ofAcetyl-L-Carnitine ( ALC) 1000mg tid. Subjects with HRPC will also receive Prednisone or Prednisolone 5mg bid, throughout the treatment with Sagopilone.

Arm 2: Placebo Comparator

Drug: Sagopilone 16 mg/m2 i.v. and Placebo tid

Subjects will receive intravenous (i.v.) infusion of Sagopilone for 3 hours on day 1 of a 3-weeks cycle. Duration of treatment is up to 6 courses. In addition, subjects will receive 21 weeks ofAcetyl-L-Carnitine (ALC) 1000mg tid. Subjects with HRPC will also receive Prednisone or Prednisolone 5mg bid, throughout the treatment with Sagopilone.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00751205

Contacts

Contact: Bayer Clinical Trials Contact

clinical-trials-contact@bayerhealthcare.com

Show 26 Study Locations

Sponsors and Collaborators

Bayer

Investigators

Study Director:

Bayer Study Director

Bayer

More Information

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Responsible Party:	Bayer Schering Pharma AG ( Therapeutic Area Head )
Study ID Numbers:	91695, EudraCT-2008-000879-26
Study First Received:	September 10, 2008
Last Updated:	January 5, 2009
ClinicalTrials.gov Identifier:	NCT00751205
Health Authority:	Belgium: Federal Agency for Medicinal Products and Health Products; France: Afssaps - French Health Products Safety Agency; Germany: Federal Institute for Drugs and Medical Devices; Italy: The Italian Medicines Agency; Spain: Spanish Agency of Medicines; The Netherlands: The Central Committee on Research Involving Human Subjects (CCMO); United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Bayer:

Peripheral Neuropathy
Prostate Carcinoma
Ovarian Carcinoma

Study placed in the following topic categories:

Prednisone
Neurotoxicity Syndromes
Genital Neoplasms, Male
Prostatic Diseases
Methylprednisolone
Gonadal Disorders
Urogenital Neoplasms
Prednisolone acetate
Ovarian Diseases
Ovarian epithelial cancer
Genital Diseases, Female
Neuromuscular Diseases
Methylprednisolone Hemisuccinate
Endocrine Gland Neoplasms

Acetylcarnitine
Ovarian cancer
Ovarian Neoplasms
Neurotoxicity syndromes
Genital Neoplasms, Female
Endocrine System Diseases
Methylprednisolone acetate
Genital Diseases, Male
Carcinoma
Peripheral Nervous System Diseases
Prednisolone
Endocrinopathy
Prostatic Neoplasms
Carnitine

Additional relevant MeSH terms:

Nootropic Agents
Vitamin B Complex
Growth Substances
Nervous System Diseases
Physiological Effects of Drugs
Pharmacologic Actions
Adnexal Diseases

Neoplasms
Neoplasms by Site
Therapeutic Uses
Vitamins
Micronutrients
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 16, 2009