Clinical Trial Result Information

Title of Study:
PREFERENCE study - A Study of Oral and Intravenous Bondronat (Ibandronate) in Patients With Breast Cancer and Bone Metastasis

Fast Facts:

Protocol number:	ML17633
Sponsor:	Roche Pharma (Schweiz) AG
Company division:	Pharmaceutical
Product name:	Bondronat
Generic name:	ibandronate
Phase of development:	IV
Therapeutic area, approved indication:	Pain; Bone Neoplasm; Neoplasm Metastasis
Date of report:	12/19/2007

Clinical study summary:
This was an open label, randomized, crossover trial to assess patients' preference for the oral or i.v. formulation of Bondronat (ibandronate). Patients were randomized to one of the two treatment groups. Patients in group A started with oral treatment while patients in group B started with i.v. treatment. At visit 5 (crossover) the treatment was switched to the other formulation (oral to i.v. treatment and vice versa). At every visit the patient completed a questionnaire on pain assessment (BPI). In addition questionnaires on quality of life (EORTC QLQ-C30) and on preference for the treatment formulation (oral vs. i.v.) were completed by the patients at baseline, crossover and final visit.

Study center(s) :
14 centers in Switzerland.

Objectives:
Primary: To evaluate patients' preference with respect to the formulation of Bondronat.
Secondary: To assess 1) bone pain; 2) Quality of Life (EORTC QLQ-C30); 3) safety and tolerability profile.

Methodology:
Patients were randomized to receive Bondronat either 50mg po daily or 6mg iv every 3-4 weeks. After 9-12 weeks, patients were crossed over to the other formulation for a further 9-12 weeks. Hematology, blood chemistry and pain assessment (BPI) were performed at all clinic visits. At the crossover (visit 5, day 63+/-3 or day 84+/-3) questionnaires on quality of life and preference of treatment were completed by the patient. Safety was assessed through the recording of adverse events, concomitant medications and radiotherapies documented, and clinical laboratory tests performed at screening and during the treatment period.

Number of patients (planned/analyzed):
Planned: 100. Enrolled: 60.

Diagnosis and main criteria for inclusion:
Female patients with breast cancer and metastatic bone disease.

Test product, dose and mode of administration or test procedure:
Bondronat (ibandronate)
Oral treatment: 50mg po for 9 - 12 weeks
i.v. treatment: 6mg iv infusion every 3-4 weeks (3 administrations)

Duration of treatment:
18-24 weeks in total (2 treatments)

Reference therapy, dose and mode of administration or reference procedure:
N/A

Criteria for evaluation (efficacy, safety):
Efficacy: Primary: Preference of treatment using patient questionnaire.
Secondary: Brief Pain Inventory (BPI); EORTC QLQ-C30.

Safety: Safety profile assessed on the basis of AEs, lab values and vital signs.

Statistical methods:
Descriptive statistics were used for summarising and analysis of efficacy parameters.

Summary (efficacy, safety, other results):
Efficacy: At baseline a total of 22 patients (52%) reported infusion and 20 patients (48%) reported tablets as the preferred treatment. The estimated 95% confidence intervals were [36.4%, 68.0%] for infusion and [32.0%, 63.6%] for tablets. At the end of treatment patients' treatment preference had shifted slightly to infusion. A total of 31 patients (72%) preferred infusion while 12 patients (28%) preferred treatment with tablets. The 95% confidence intervals were [56.3%, 84.7%] for infusion and [15.3%, 43.7%] for tablets.
For the bone pain questionnaires the paired differences between the treatments were calculated for every single score and for the total score. No difference between oral and i.v. treatment could be found from observation of the paired differences in the single scores of the BPI questionnaire. Furthermore, no significant difference in calculated total score of BPI could be observed.
For the functional scales, the symptom scales and the global health status assessed in the EORTC QLQ-C30 questionnaire, the paired differences at the end of each treatment were calculated. No significant difference between oral and i.v. treatment could be observed in quality of life.

Safety: During the study the most frequent reported adverse events were nausea (21% oral, 21% i.v.), anorexia (12% oral, 10% i.v.), fatigue (7% oral, 14% i.v.), dyspnea (12% oral, 5% i.v.), arthralgia (3% oral, 14% i.v) and diarrhea (7% oral, 10% i.v.). Ten patients (17%) recorded serious adverse events starting during oral treatment and five patients (9%) recorded serious adverse events starting during i.v. treatment. Three patients reported adverse events leading to death. No SAEs were considered as related to treatment.

Conclusions:
Bondronat administered either i.v. or po was generally well tolerated with a safety profile consistent with that of previous studies. While approximately equal percentages of patients preferred each formulation at the beginning, a trend was observed towards preference of i.v. treatment by the end of the study. Nevertheless, approximately one third of patients preferred oral treatment after exposure to both formulations, emphasizing the relevance of both ways of administration for different groups of patients. Neither new or unexpected adverse events nor clinically relevant changes in laboratory parameters or vital signs were observed during the course of the study, underscoring the safety of both formulations of Bondronat in the treatment of metastatic bone disease due to breast cancer.

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