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

Prostate Cancer Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00751205
• Other study ID #: 91695
• Secondary ID: 2008-000879-26
• Status: Completed
• Phase: Phase 2
• First received: September 10, 2008
• Last updated: October 27, 2014
• Start date: August 2008
• Est. completion date: August 2010

Study information

• Verified date: October 2014
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health ProductsFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesItaly: The Italian Medicines AgencySpain: Spanish Agency of MedicinesThe Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: August 2010
• Est. primary completion date: February 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Ovarian Cancer
• Peripheral Nervous System Diseases
• Prostate Cancer

Intervention

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.
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Countries where clinical trial is conducted

Belgium,  France,  Germany,  Italy,  Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Yes
Secondary	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	Yes
Secondary	Efficacy of ALC: Percentage of discontinuations due to neuropathy.		Start of treatment to safety Follow-up	No
Secondary	Safety of Sagopilone in combination with ALC.		Baseline to Safety follow-up	Yes
Secondary	Efficacy of Sagopilone: 'best overall response' according to modRECIST criteria		Start treatment to End of Treatment	No
Secondary	Efficacy of Sagopilone: 'best overall response' according to CA-125 or PSA response		Start treatment to End of Treatment	No
Secondary	Efficacy of Sagopilone: Time to disease progression, Progression-free survival		Start treatment to Progression or Death	No
Secondary	Efficacy of Sagopilone: Duration of response		Start treatment to Progression or Death	No
Secondary	Efficacy of Sagopilone: WHO performance status.		Screening to end of Treatment	No
Secondary	Pharmacokinetic: Sagopilone concentrations (optional)		Day 1,2,3,5,15 of cycle 1 and day2	No
Secondary	Pharmacokinetic: ALC concentrations		radomisation, day 1 of cycle 1 and 2	No
Secondary	Pharmacogenomics (optional): in tumor tissue, blood and ascites		Blood sample at screening, tissue sample and ascites whenever available	No

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