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

October 27, 2014 updated by: Bayer

(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.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

150

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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.
Start of Sagopilone treatment until at most 6 cycles + 1 month.

Secondary Outcome Measures

Outcome Measure
Time Frame
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
Start of treatment to safety Follow-up
Efficacy of ALC: Percentage of discontinuations due to neuropathy.
Time Frame: Start of treatment to safety Follow-up
Start of treatment to safety Follow-up
Safety of Sagopilone in combination with ALC.
Time Frame: Baseline to Safety follow-up
Baseline to Safety follow-up
Efficacy of Sagopilone: 'best overall response' according to modRECIST criteria
Time Frame: Start treatment to End of Treatment
Start treatment to End of Treatment
Efficacy of Sagopilone: 'best overall response' according to CA-125 or PSA response
Time Frame: Start treatment to End of Treatment
Start treatment to End of Treatment
Efficacy of Sagopilone: Time to disease progression, Progression-free survival
Time Frame: Start treatment to Progression or Death
Start treatment to Progression or Death
Efficacy of Sagopilone: Duration of response
Time Frame: Start treatment to Progression or Death
Start treatment to Progression or Death
Efficacy of Sagopilone: WHO performance status.
Time Frame: Screening to end of Treatment
Screening to end of Treatment
Pharmacokinetic: Sagopilone concentrations (optional)
Time Frame: Day 1,2,3,5,15 of cycle 1 and day2
Day 1,2,3,5,15 of cycle 1 and day2
Pharmacokinetic: ALC concentrations
Time Frame: radomisation, day 1 of cycle 1 and 2
radomisation, day 1 of cycle 1 and 2
Pharmacogenomics (optional): in tumor tissue, blood and ascites
Time Frame: Blood sample at screening, tissue sample and ascites whenever available
Blood sample at screening, tissue sample and ascites whenever available

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Bayer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2008

Primary Completion (Actual)

February 1, 2010

Study Completion (Actual)

August 1, 2010

Study Registration Dates

First Submitted

September 10, 2008

First Submitted That Met QC Criteria

September 10, 2008

First Posted (Estimate)

September 11, 2008

Study Record Updates

Last Update Posted (Estimate)

October 28, 2014

Last Update Submitted That Met QC Criteria

October 27, 2014

Last Verified

October 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 91695
  • 2008-000879-26 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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