Clinical trial NCT00751205: Prevention of Sagopilone-induced Neurotoxicity With Acetyl-L-Carnitine (ALC)
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Ovarian Cancer
Keywords: Peripheral Neuropathy
Prostate Carcinoma
Ovarian Carcinoma
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2008-09-11
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Overall incidence of peripheral neuropathy (any grade) during at most 6 cycles of Sagopilone treatment, based on the Adverse Events.
timeFrame: Start of Sagopilone treatment until at most 6 cycles + 1 month.
Secondary outcomes:
measure: Efficacy of ALC: incidence of neuropathy of grade 3 or 4, time to onset of neuropathy, duration of neuropathy.
timeFrame: Start of treatment to safety Follow-up
measure: Efficacy of ALC: Percentage of discontinuations due to neuropathy.
timeFrame: Start of treatment to safety Follow-up
measure: Safety of Sagopilone in combination with ALC.
timeFrame: Baseline to Safety follow-up
measure: Efficacy of Sagopilone: 'best overall response' according to modRECIST criteria
timeFrame: Start treatment to End of Treatment
measure: Efficacy of Sagopilone: 'best overall response' according to CA-125 or PSA response
timeFrame: Start treatment to End of Treatment
measure: Efficacy of Sagopilone: Time to disease progression, Progression-free survival
timeFrame: Start treatment to Progression or Death
measure: Efficacy of Sagopilone: Duration of response
timeFrame: Start treatment to Progression or Death
measure: Efficacy of Sagopilone: WHO performance status.
timeFrame: Screening to end of Treatment
measure: Pharmacokinetic: Sagopilone concentrations (optional)
timeFrame: Day 1,2,3,5,15 of cycle 1 and day2
measure: Pharmacokinetic: ALC concentrations
timeFrame: radomisation, day 1 of cycle 1 and 2
measure: Pharmacogenomics (optional): in tumor tissue, blood and ascites
timeFrame: Blood sample at screening, tissue sample and ascites whenever available
Other outcomes:
Locations:
city: Bruxelles - Brussel
country: Belgium
city: Caen
country: France
city: Montpellier Cedex
country: France
city: Nantes
country: France
city: Paris
country: France
city: Villejuif
country: France
city: Tübingen
country: Germany
state: Baden-Württemberg
city: Rostock
country: Germany
state: Mecklenburg-Vorpommern
city: Bonn
country: Germany
state: Nordrhein-Westfalen
city: Essen
country: Germany
state: Nordrhein-Westfalen
city: Essen
country: Germany
state: Nordrhein-Westfalen
city: Magdeburg
country: Germany
state: Sachsen-Anhalt
city: Meldola
country: Italy
state: Forlì
city: Bologna
country: Italy
city: Rimini
country: Italy
city: Roma
country: Italy
city: Amsterdam
country: Netherlands
city: Amsterdam
country: Netherlands
city: Leiden
country: Netherlands
city: Maastricht
country: Netherlands
city: Leicester
country: United Kingdom
state: Leicestershire
city: Northwood
country: United Kingdom
state: Middlesex
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: Campone M, Berton-Rigaud D, Joly-Lobbedez F, Baurain JF, Rolland F, Stenzl A, Fabbro M, van Dijk M, Pinkert J, Schmelter T, de Bont N, Pautier P. A double-blind, randomized phase II study to evaluate the safety and efficacy of acetyl-L-carnitine in the prevention of sagopilone-induced peripheral neuropathy. Oncologist. 2013;18(11):1190-1. doi: 10.1634/theoncologist.2013-0061. Epub 2013 Oct 8.