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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT00751205
First received: September 10, 2008
Last updated: October 20, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Prostate Cancer
Ovarian Cancer
Drug: Sagopilone 16 mg/m^2 i.v., Acetyl-L-Carnitine (ALC) 1000 mg tid, HRPC only: Prednisone or Prednisolone 5 mg bid
Drug: Sagopilone 16 mg/m^2 i.v. and placebo 1000 mg tid, HRPC only: Prednisone or Prednisolone 5 mg bid
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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.

Resource links provided by NLM:


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: Start of Sagopilone treatment until at most 6 cycles + 1 month. ] [ 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 ]

Enrollment: 150
Study Start Date: August 2008
Study Completion Date: August 2010
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1 Drug: 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.
Placebo Comparator: Arm 2 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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
Belgium
Bruxelles - Brussel, Belgium, 1200
France
Caen, France, 14076
Montpellier Cedex, France, 34298
Nantes, France, 44805
Paris, France, 75012
Villejuif, France, 94805
Germany
Tübingen, Baden-Württemberg, Germany, 72076
Rostock, Mecklenburg-Vorpommern, Germany, 18059
Bonn, Nordrhein-Westfalen, Germany, 53105
Essen, Nordrhein-Westfalen, Germany, 45122
Essen, Nordrhein-Westfalen, Germany, 45147
Magdeburg, Sachsen-Anhalt, Germany, 38108
Italy
Meldola, Forlì, Italy, 47014
Bologna, Italy, 40138
Rimini, Italy, 47900
Roma, Italy, 00189
Netherlands
Amsterdam, Netherlands, 1081 HV
Amsterdam, Netherlands, 1066 CX
Leiden, Netherlands, 2333 ZA
Maastricht, Netherlands, 6229 HX
United Kingdom
Leicester, Leicestershire, United Kingdom, LE1 5WW
Northwood, Middlesex, United Kingdom, HA6 2RN
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
No publications provided

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00751205     History of Changes
Other Study ID Numbers: 91695, 2008-000879-26
Study First Received: September 10, 2008
Last Updated: October 20, 2013
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
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

Additional relevant MeSH terms:
Acetylcarnitine
Prostatic Neoplasms
Ovarian Neoplasms
Peripheral Nervous System Diseases
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Endocrine Gland Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Endocrine System Diseases
Gonadal Disorders
Neuromuscular Diseases
Nervous System Diseases
Methylprednisolone acetate
Prednisolone acetate
Prednisone
Prednisolone
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone hemisuccinate
Prednisolone phosphate
Carnitine
Epothilones
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on September 18, 2014