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

Bayer

Status and phase: Completed; Phase 2

Conditions: Ovarian Cancer; Prostate Cancer

Treatments: Drug: Sagopilone 16 mg/m^2 i.v. and placebo 1000 mg tid, HRPC only: Prednisone or Prednisolone 5 mg bid; Drug: Sagopilone 16 mg/m^2 i.v., Acetyl-L-Carnitine (ALC) 1000 mg tid, HRPC only: Prednisone or Prednisolone 5 mg bid

Study type: Interventional

Funder types: Industry

Identifiers

NCT00751205

2008-000879-26 (EudraCT Number)

91695

Details and patient eligibility

About

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.

Enrollment: 150 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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150 participants in 2 patient groups, including a placebo group

Arm 1

Experimental group

Treatment:

Drug: Sagopilone 16 mg/m^2 i.v., Acetyl-L-Carnitine (ALC) 1000 mg tid, HRPC only: Prednisone or Prednisolone 5 mg bid

Arm 2

Placebo Comparator group

Treatment:

Drug: Sagopilone 16 mg/m^2 i.v. and placebo 1000 mg tid, HRPC only: Prednisone or Prednisolone 5 mg bid