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

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

ChemIDplus related topics:

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:	January 2010
Estimated Primary Completion Date:	December 2009 (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 of prophylaxis with Acetyl-L-Carnitine (ALC) Placebo tid.
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 of prophylaxis with Placebo tid.

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 f or 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

Locations


Belgium
		Recruiting
	BRUXELLES - BRUSSEL, Belgium, 1200

France
		Recruiting
	Nantes, France, 44805
		Not yet recruiting
	SAINT HERBLAIN, France, 44805
		Not yet recruiting
	RENNES CEDEX, France, 35062
		Not yet recruiting
	VILLEJUIF CEDEX, France, 94305
		Not yet recruiting
	Caen, France, 14076
		Not yet recruiting
	PARIS CEDEX 20, France, 75960
		Not yet recruiting
	MONTPELLIER CEDEX, France, 34298
		Terminated
	BORDEAUX CEDEX, France, 33076
		Not yet recruiting
	LYON CEDEX, France, 69008

Germany, Baden-Württemberg
		Not yet recruiting
	Tübingen, Baden-Württemberg, Germany, 72076

Germany, Mecklenburg-Vorpommern / 309
		Not yet recruiting
	Rostock, Mecklenburg-Vorpommern / 309, Germany, 18059

Germany, Nordrhein-Westfalen
		Not yet recruiting
	Essen, Nordrhein-Westfalen, Germany, 45147

Italy
		Not yet recruiting
	Bologna, Italy, 40138
		Not yet recruiting
	Roma, Italy, 00189
		Not yet recruiting
	Rimini, Italy, 47900

Italy, Forlì
		Not yet recruiting
	Meldola, Forlì, Italy, 47014

Netherlands
		Not yet recruiting
	AMSTERDAM, Netherlands, 1066 CX
		Not yet recruiting
	MAASTRICHT, Netherlands, 6229 HX
		Not yet recruiting
	AMSTERDAM, Netherlands, 1081 HV

Spain
		Not yet recruiting
	Salamanca, Spain, 37007
		Not yet recruiting
	Guadalajara, Spain, 19002

United Kingdom
		Not yet recruiting
	Glasgow, United Kingdom, G12 0YN

United Kingdom, Leicestershire
		Not yet recruiting
	Leicester, Leicestershire, United Kingdom, LE1 5WW

United Kingdom, Middlesex
		Not yet recruiting
	Northwood, Middlesex, United Kingdom, HA6 2RN

Sponsors and Collaborators

Bayer

Investigators


Study Director:	Bayer Study Director	Bayer

More Information

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Responsible Party:	Bayer Schering AG ( Therapeutic Area Head )
Study ID Numbers:	91695, 311602, 2008-000879-26, REASON
First Received:	September 10, 2008
Last Updated:	September 22, 2008
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; 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:

Ovarian cancer

Ovarian Neoplasms

Prostatic Diseases

Genital Neoplasms, Male

Neurotoxicity Syndromes

Gonadal Disorders

Neurotoxicity syndromes

Genital Neoplasms, Female

Endocrine System Diseases

Urogenital Neoplasms

Ovarian Diseases

Ovarian epithelial cancer

Genital Diseases, Male

Carcinoma

Genital Diseases, Female

Neuromuscular Diseases

Peripheral Nervous System Diseases

Endocrinopathy

Prostatic Neoplasms

Carnitine

Acetylcarnitine

Endocrine Gland Neoplasms

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 October 06, 2008

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