Pamidronate Administration in Breast Cancer Patients With Bone Metastases

Sponsor

Spanish Breast Cancer Research Group (Other)

Overall Status

Completed

CT.gov ID

NCT00128297

Collaborator

Novartis (Industry)

152

Enrollment

Location

Arms

43.5

Actual Duration (Months)

3.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The study objective is to evaluate the differences, in terms of first occurrence of a skeletal event, in patients with breast cancer and symptomatic bone metastases, when pamidronate is administered during 2 years, or when it is administered during 6 months, followed by a six month rest period, and again a 6 month treatment period.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer Neoplasm Metastasis	Drug: Pamidronate	Phase 4

Detailed Description

Background: Pamidronate (PMT) is effective in reducing skeletal related events (SRE) in breast cancer (BC) patients with bone metastasis (BM). Its best way of administration and optimum treatment duration are still to be determined.

Objective: evaluate the efficacy of continuous administration (arm A) vs. alternate administration (arm B) of PMT to delay time to first SRE in BC pt presenting with symptomatic BM.

Methods: patients aged >18, Eastern Cooperative Oncology Group (ECOG) performance status ≥ 2, adequate renal function, and BC symptomatic BM were eligible. BM was defined as presence of 3 or more hot spots (HS) in skeletal scintigraphy (SS), or any number of HS in SS if osteolytic, osteoblastic or mixed bone lesions determined by radiography, or 2 or less HS in SS if magnetic resonance or CT scan confirmation of BM. Symptomatic BM was defined as pain associated to SS HS, or SRE (pathological fractures or spine cord compression or radiation bone treatment or tumour induced hypercalcemia), or treatment with analgesia due to bone pain. Patients were allowed up to 1 previous chemotherapy and 2 previous hormone therapy lines for metastatic disease. Antineoplastic therapy could be changed at any time during the study. Eligible patients were stratified (isolated bone metastasis or associated to node or skin lesions vs. bone metastasis associated to visceral disease) and randomized to receive 2 hour-iv. PMT 90 mg every 3-4 weeks for 18 months (arm A) or iv. PMT 90 mg every 3-4 weeks for 6 months, followed by a 6 months rest, and a new 6 months on-treatment period (arm B). Quality of Life (QoL) was measured with short form (SF)-36 questionnaire.

Study Design

Study Type:

Interventional

Actual Enrollment :

152 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

Randomized, Multicentric Phase IV Clinical Trial for the Administration of Pamidronate in Breast Cancer Patients With Bone Metastases

Actual Study Start Date :

Oct 18, 2000

Actual Primary Completion Date :

Jun 4, 2004

Actual Study Completion Date :

Jun 4, 2004

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm A: continuous administration Pamidronate 90 mg/m2 iv every 3-4 weeks, during 18 months	Drug: Pamidronate Other Names: Aredia
Experimental: Arm B: alternate administration Pamidronate 90 mg/m2 iv every 3-4 weeks, during 6 months, followed by a 6 month rest, and a new 6 months treatment period.	Drug: Pamidronate Other Names: Aredia

Arm

Intervention/Treatment

Active Comparator: Arm A: continuous administration

Pamidronate 90 mg/m2 iv every 3-4 weeks, during 18 months

Drug: Pamidronate

Other Names:

Aredia

Experimental: Arm B: alternate administration

Pamidronate 90 mg/m2 iv every 3-4 weeks, during 6 months, followed by a 6 month rest, and a new 6 months treatment period.

Drug: Pamidronate

Other Names:

Aredia

Outcome Measures

Primary Outcome Measures

Pamidronate efficacy to prevent first skeletal event: time until the appearance of the first skeletal event [18 months]
The main variable of evaluation is the time until the appearance of the first skeletal event. Skeletal event is defined as pathological bone fracture, or spine cord compression, or radiation bone treatment, or tumour induced hypercalcemia

Secondary Outcome Measures

Number of skeletal events per treatment arm [18 months]
The main variable of evaluation is the time until the appearance of the first skeletal event per arm.
Quality of life: Short Form (SF)-36 questionnaire [18 months]
Quality of Life (QoL) was measured with Short Form (SF)-36 questionnaire, which is a 36 item, patient-reported survey of patient health. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score, the more disability, and the higher the score the less disability (a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability). The eight sections are vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning and mental health. It will be completed since baseline visit and during all treatment period delivered to the patient before the start of each visit.
Overall survival (OS) [18 months]
OS will be determined from the date of randomization until the date of death for any reason.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Written informed consent.
Up to two previous or current hormone therapy treatments for metastatic breast cancer are allowed.
Normal or borderline renal function (serum creatinine < 1.5 x upper normal limit [UNL]).
Normal calcium levels in serum, or slightly non-symptomatic high levels (< 1.25 x UNL).
Performance status 0, I or II in World Health Organization (WHO) scale.

Exclusion Criteria:

Treatment with bisphosphonates in the 30 previous days, or any time if the indication was treatment of metastatic bone lesions.
Treatment with bisphosphonates is only allowed if the indication is hypercalcaemia.
Metastases in central nervous system (CNS).
Hypersensitivity to bisphosphonates or other components of the formula.
Pregnant or lactating women.
Previous or current treatment with a second chemotherapy line or a third hormone therapy line for metastatic disease.