(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. - REASO

• Conditions: - Advanced refractory or relapsed ovarian cancer - Patients with metastatic hormone-refractory prostate cancer; MedDRA version: 9.1Level: LLTClassification code 10066697Term: Ovarian cancer recurrent; MedDRA version: 9.1Level: LLTClassification code 10036909Term: Prostate cancer metastatic

• Registration Number: EUCTR2008-000879-26-NL
• Lead Sponsor: Bayer Schering Pharma AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-06-02
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 140

Inclusion Criteria

All of the following criteria have to be met for inclusion of a patient into the study:
1) Histologically or cytologically proven
a) Epithelial ovarian, peritoneal cavity or Fallopian tube cancer (except mucinous
or clear cell tumors) or
b) Adenocarcinoma of the prostate

Specific for HRPC:
2) At least 1 unidimensionally measurable lesion (suitable for RECIST evaluation) or
for patients without measurable disease PSA value = 5 ng/mL
3) Progression of disease despite adequate androgen-inhibiting hormone therapy,
demonstrated by:
- rising PSA on at least 2 consecutive measurements taken at least 7 days apart.
The last measurement must be = 50% greater than the lowest PSA value
achieved under the last previous treatment.
- PSA at least 4 ng/ml
4) PSA value at screening (4 to 6 weeks after cessation of antiandrogen treatment)
must continue to be elevated
5) Serum testosterone < 50 ng/mL (ongoing treatment with luteinizing hormone-
releasing hormone (LHRH) analogues or orchiectomy)

Specific for Ovarian cancer
6) At least 1 unidimensionally 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.
7) Progression of disease or symptomatic relapse after previous therapy (elevated
CA 125 levels alone are insufficient for inclusion).

General
8) Males or females = 18 years of age
9) WHO performance status 0 to 1
10) No clinical residual neuropathy (CTCAE Grade 0 at baseline)
11) Adequate recovery from previous surgery, radiation, and
chemotherapy (excluding alopecia)
12) Adequate function of major organs and systems
• Hematopoietic: - Hemoglobin: = 10 g/dL
- WBC:= 3,000/mm3
- Absolute neutrophil count:= 1,000/mm3
- Platelet count: = 100,000/mm3
• Hepatic: - Total bilirubin:normal
- AST/ALT: = 3 times the upper limit of normal (= 5 x upper limit of
normal for patients with liver involvement of their cancer)
• Renal: - Creatinine: = 2 mg/dL
• Cardiovascular: - No symptomatic congestive heart failure
- No unstable angina pectoris
- No arrhythmia needing continuous treatment
- No uncontrolled hypertension
- No MI within past 6 months
- No cerebrovascular insult within past 6 months
• No other uncontrolled concurrent illness
13) Survival expectation =3 months
14) Negative pregnancy test at enrollment (females of childbearing potential only)
15) Agreement to use highly effective contraception methods (intra-uterine
contraceptive device IUCD, condoms, oral contraceptives, or other adequate
barrier contraception) in females of child-bearing potential and adequate barrier
birth control measures in men during the course of the trial and two weeks after
the completion of the trial.
16) Written informed consent

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1

Exclusion Criteria

1) Candidacy for curative resection
2) Symptomatic brain metastases requiring whole-brain irradiation
3) Congenital bleeding diathesis, acquired coagulopathy or patients receiving full
dose of anticoagulants for the treatment of thromboembolism
4) Any concomitant malignancy: the following exceptions are allowed:
a) Non-melanoma skin cancer
b) Carcinoma in situ of the cervix
c) Malignancy with definitive treatment = 5 years ago without relapse
5) History of organ allograft
6) Diabetes mellitus (even if controlled only by special diet)
7) History of chronic hepatitis B or C, or known HIV infection
8) Seizure disorder requiring medication (such as steroids or anti-
epileptics)
9) Inability to swallow oral medications
10) Any malabsorption condition
11) Active infection
12) Breast feeding
13) Hypersensitivity to the active substance or to any of the excipients of any of the
study medications
14) Any condition that in the opinion of the investigator could hamper the compliance
with the study protocol.

Excluded therapies and medications, previous and concomitant:
15) Concomitant use of neurotoxic drugs
16) Concomitant use of compounds that have potentially positive effects towards
symptoms of neuropathy
17) Time period since prior therapy and start of study treatment:
a) Prior radiotherapy: < 4 weeks
b) Prior flutamide or cyproterone acetate: < 4 weeks
c) Prior bicalutamide or nilutamide: < 6 weeks
18) Anticancer chemotherapy or immunotherapy during the study or within 4 weeks
of study entry. Mitomycin C or nitrosureas should not be given within 6 weeks of
study entry.
19) Major surgery less than 28 days prior to start of treatment
20) Prior treatment with epothilones
21) Use of any investigational drug within 4 weeks before start of study treatment
22) Alcohol abuse or abuse of other drugs with neurotoxic potential

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Primary Objective:<br>to demonstrate the superiority of ALC over placebo in the prevention of Sagopilone-induced peripheral neuropathy <br>;Secondary Objective: Secondary Objectives:<br>•To assess the safety and efficacy of Sagopilone in combination with ALC<br>•To assess the pharmacokinetics of Sagopilone in combination with ALC<br>•To assess the pharmacogenomics of Sagopilone in combination with ALC<br>;Primary end point(s): Overall incidence of peripheral neuropathy (any grade) during at most 6 cycles of sagopilone treatment, based on Adverse Events.