Pharmacokinetic Study of Tesmilifene (YMB1002) Plus Epirubicin and Cyclophosphamide in Metastatic Breast Cancer

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT00364754
• Date of registration: 15/08/2006
• Prospective Registration: No
• Primary sponsor: YM BioSciences
• Public title: Pharmacokinetic Study of Tesmilifene (YMB1002) Plus Epirubicin and Cyclophosphamide in Metastatic Breast Cancer
• Scientific title: A PHARMACOKINETIC INTERACTION PHASE I, MULTI-CENTRE, OPEN-LABEL, CROSS-OVER Study Evaluating the Effect of Tesmilifene on the Plasma Pharmacokinetics of Epirubicin and Cyclophosphamide in Patients With Metastatic/Recurrent Breast Cancer
• Date of first enrolment: May 2004
• Target sample size: 28
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00364754
• Study type: Interventional
• Study design: Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
• Phase: Phase 1

Countries of recruitment

Georgia, Russian Federation, Ukraine

Contacts

• Name: Igor Sherman, PhD
• Affiliation: YM BioSciences

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Patients with documented histological/cytological proof of metastatic and/or
recurrent breast cancer suitable for treatment with epirubicin and cyclophosphamide.
Patients with locally advanced and inoperable lesions are also eligible.

2. Previous therapy:

- If patients have had hormone-responsive disease, randomization is permitted
after 6 weeks off anti-hormonal therapy or 5 half lives (whichever is shorter)
unless there is evidence of progressive disease in which case patients could be
randomized earlier.

- No previous exposure to anthracycline/anthracenedione-based chemotherapy.

- Patients may have received non-anthracycline/anthracenedione based adjuvant
chemotherapy, completed a minimum of 4 weeks prior to randomization. Patients
must not have had previous chemotherapy for metastatic disease.

- Immunotherapy and experimental therapy must stop a minimum of 4 weeks prior to
randomization.

- A minimum of four weeks must have elapsed between the end of prior radiotherapy
and randomization. Exceptions will be made, however, for palliative
radiotherapy which involves no more than 30% of bone marrow.

3. ECOG status of 0, 1 or 2.

4. Female, aged 18 to 55 years.

5. Life expectancy of at least 6 months.

6. Patients must be willing and able to follow instructions and make all required study
visits.

7. Patients must be willing and able to give written consent to participate in this
study.

8. Disease free interval less than or equal to 36 months.

9. Normal organ and marrow function

10. Negative serum or urine pregnancy test within 72 hours prior to randomization and
must be on a medically recognized form of birth control that is approved by the
investigator.

11. Negative blood tests for HIV and Hepatitis B and C within 4 weeks prior to
randomisation.

Exclusion Criteria:

1. Previous malignancies, excluding curatively treated basal or squamous cell carcinoma
of the skin or in-situ cervical cancer or any other cancer treated more than five
years prior to study entry and presumed cured.

2. Known brain or meningeal metastases

3. Use of chemotherapeutic agents for any malignancy within 4 weeks prior to study entry
or those who have not recovered from adverse events due to agents administered more
than 4 weeks earlier.

4. Treatment with any other investigational drug within the preceding four weeks.

5. Pregnant and breast-feeding females.

6. History of seizure disorder.

7. Clinical evidence of congestive heart failure, recent myocardial infarction within 6
months, uncontrolled arterial hypertension, unstable angina, cardiomyopathy or
arterial or ventricular clinically significant arrhythmias even if medically
controlled.

8. Clinically significant cardiovascular, pulmonary, renal, endocrine, hepatic,
respiratory, neurologic, psychiatric, immunologic, gastrointestinal, haematologic,
metabolic or any other condition or laboratory abnormality that, in the opinion of
the Investigator or Medical Director of YM BioSciences Inc., makes the patient
unsuitable for participation in the study.

9. Known allergy or hypersensitivity to test article ingredients.

10. Patients on COX 1 or 2 prostaglandin inhibitors (e.g. ASA, other NSAID's, Celcbrex®,
Vioxx® ) who can not comply with guidelines or concomitant therapy.

11. Patients on H1 antagonists as detailed in the protocol who can not comply with
guidelines or concomitant therapy



Age minimum: 18 Years
Age maximum: 55 Years
Gender: Female

Health Condition(s) or Problem(s) studied

Metastatic/Recurrent Breast Cancer

Intervention(s)

Drug: Tesmilifene (YMB 1002)

Primary Outcome(s)

The distribution of the pharmacokinetic variables will be summarized by treatment. The variables AUC and CMAX expressed as geometric means and ratios of geometric means on the original scale of measurement.

Secondary Outcome(s)

Although response is not the endpoint of this trial, patients with measurable disease will be assessed by standard institutional criteria.

The tesmilifene concentration, haematology and biochemistry values will be tabulated across time.

Blood pressure, temperature, pulse and respiration will be tabulated across time and shift tables will be presented.

Adverse experiences will be collected and graded using the NCI Expanded Common Terminology Criteria for Adverse Events version 3.0.

Secondary ID(s)

YMB1002 202

Source(s) of Monetary Support

Please refer to primary and secondary sponsors