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

Phase 2

Completed

• Conditions: Ovarian Cancer; Prostate Cancer

• Registration Number: NCT00751205
• Lead Sponsor: Bayer

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design

Study Timeline

• Study Start: 2008-08
• Study First Submitted: 2008-09-10
• Study First Submitted QC: 2008-09-10
• Study First Posted: 2008-09-11
• Primary Completion: 2010-02
• Study Completion: 2010-08
• Status Verified: 2014-10
• Last Update Submitted: 2014-10-27
• Last Update Posted: 2014-10-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 150

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%)

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Overall incidence of peripheral neuropathy (any grade) during at most 6 cycles of Sagopilone treatment, based on the Adverse Events.	Start of Sagopilone treatment until at most 6 cycles + 1 month.

Secondary Outcome Measures

Name	Time	Method
Efficacy of ALC: incidence of neuropathy of grade 3 or 4, time to onset of neuropathy, duration of neuropathy.	Start of treatment to safety Follow-up
Pharmacokinetic: ALC concentrations	radomisation, day 1 of cycle 1 and 2
Efficacy of ALC: Percentage of discontinuations due to neuropathy.	Start of treatment to safety Follow-up
Safety of Sagopilone in combination with ALC.	Baseline to Safety follow-up
Efficacy of Sagopilone: 'best overall response' according to modRECIST criteria	Start treatment to End of Treatment
Efficacy of Sagopilone: 'best overall response' according to CA-125 or PSA response	Start treatment to End of Treatment
Efficacy of Sagopilone: Time to disease progression, Progression-free survival	Start treatment to Progression or Death
Efficacy of Sagopilone: Duration of response	Start treatment to Progression or Death
Efficacy of Sagopilone: WHO performance status.	Screening to end of Treatment
Pharmacokinetic: Sagopilone concentrations (optional)	Day 1,2,3,5,15 of cycle 1 and day2
Pharmacogenomics (optional): in tumor tissue, blood and ascites	Blood sample at screening, tissue sample and ascites whenever available