Back to resultsPegylated Liposomal Doxorubicin (Caelyx(R)) as Monotherapy in Elderly Patients With Locally Advanced and/or Metastatic Breast Cancer (Study P05059)
Primary Purpose
Breast Neoplasms
Status
Terminated
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Caelyx (pegylated liposomal doxorubicin; SCH 200746)
Sponsored by
About this trial
This is an interventional treatment trial for Breast Neoplasms
Eligibility Criteria
Inclusion Criteria:
Patients meeting the following criteria will be eligible for enrollment.
- Female patients with histologic or cytologic diagnosis of breast cancer that is locally advanced or metastatic, and not amenable to surgery.
- Age >= 65 years.
- World Health Organization (WHO) Performance Status 0 - 2
- Measurable disease in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Patients with bone metastasis can also be included but will be evaluated according to WHO criteria. Patients with non-measurable disease can also be included.
- Left ventricular ejection fraction (LVEF) >= 50% verified by ultrasound cardiography (UCG); no clinical signs of heart disease.
Normal organ function, except due to disease involvement, however maximum deviation:
- S-creatinine <= 1.5 x upper normal limit;
- Bilirubin <= 2 x upper normal limit;
- Alanine aminotransferase (ALAT) and/or aspartate aminotransferase (ASAT) <= 3 x upper normal limit. In case of liver metastases, ALAT and/or ASAT <= 5 x upper normal limit.
Adequate bone marrow function, ie:
- Platelets >= 100 x 10^9/L;
- Neutrophils >= 1.5 x 10^9/L;
- White Blood Cell (WBC) >= 3.0 x 10^9/L;
- Hemoglobin > 90 g/L.
- Life expectancy >= 12 weeks.
- Patients having received oral and written information and having provided written informed consent.
Exclusion Criteria:
Patients will not be enrolled if any of the following conditions apply.
- Previous chemotherapy for metastatic disease. (The patient may have received previous endocrine therapy or single-drug Herceptin. Intrapleural or intrapericardial Novantrone is allowed.)
- Recurrence <= 12 months after adjuvant anthracycline-containing treatment and/or prior doxorubicin > 300 mg/m^2 or epirubicin > 540 mg/m^2.
- Myocardial infarction within 6 months of planned inclusion.
- Symptomatic brain metastases.
- Human Epidermal growth factor Receptor 2 (HER-2) positivity eligible for treatment with trastuzumab, or estrogen receptor (ER) positivity eligible for hormonal therapy.
- Allergy to anthracyclines.
- Uncontrolled infection.
- Other not radically treated malignancy.
- Other disease or condition contraindicating treatment or not allowing follow-up.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Caelyx
Arm Description
Outcomes
Primary Outcome Measures
Time to Treatment Failure (Defined as Progression of Disease [According to the Response Evaluation Criteria in Solid Tumors (RECIST) or World Health Organization (WHO) Criteria] or Unacceptable Toxicity Leading to Discontinuation of Treatment or Death).
Treatment failure was defined as progression of disease (according to the RECIST or WHO criteria) or unacceptable toxicity leading to discontinuation of treatment or death. Progressive Disease according to RECIST response criteria: >=20% increase in the sum of the Longest Diameter of target lesions or unequivocal progression of non-target lesions. Appearance of new lesions will also constitute progressive disease. Progressive Disease according to WHO response criteria: Increase in size of existing lesions or appearance of new lesions.
Secondary Outcome Measures
Number of Patients With Stable Disease (SD) as Best Response
Response was calculated according to RECIST criteria except for bone metastasis where WHO criteria was used. For patients with skeletal disease only, WHO criteria was used. For patients with measurable disease according to RECIST as well as bone metastasis, both RECIST & WHO were used.
RECIST response criteria for SD required steady state of response of at least 9 weeks duration. There may be no appearance of new lesions.
WHO response criteria for SD required no significant change for at least 8 weeks.
Number of Patients With Partial Response (PR) as Best Response
Response was calculated according to RECIST criteria except for bone metastasis where WHO criteria was used. For patients with skeletal disease only, WHO criteria was used. For patients with measurable disease according to RECIST as well as bone metastasis, both RECIST & WHO were used.
RECIST PR criteria required >=30% decrease in certain target lesions & no increase in size of non-target lesions or appearance of new lesions
WHO PR criteria required partial decrease in size of lytic lesions, recalcification of lytic lesions, or decreased density of blastic lesions for >=4 wks
Number of Patients With Progressive Disease (PD) as Best Response
Response was calculated according to RECIST criteria except for bone metastasis where WHO criteria was used. For patients with skeletal disease only, WHO criteria was used. For patients with measurable disease according to RECIST as well as bone metastasis, both RECIST & WHO were used.
RECIST PD criteria required >=20% increase in certain target lesions OR progression of non-target lesions, or appearance of new lesions
WHO PD criteria required increase in size of existing lesions or appearance of new lesions.
Number of Patients Requiring Dose Reduction
The protocol contains instructions to reduce the Caelyx dose according to specific schedules, in cases necessary due to reasons such as hematological toxicity, non-hematological toxicity, cardiotoxicity, or other toxic side-effects of treatment reducing quality of life etc.
Time to Response
Response can be partial (>=30% decrease in the sum of Longest Diameter of target lesions, determined by two observations not less than 4 weeks apart; no unequivocal increase in the size of non-target lesions or the appearance of new lesions may occur) or complete (disappearance of all clinical evidence of tumor determined by 2 observations not less than 4 weeks apart), whichever status is recorded first.
Duration of Response
Duration of response is defined as the time span from the first evaluation that shows response until the first evaluation that shows progression. Where patients did not show progress, duration of response was measured from the first evaluation that showed response until they discontinued the study.
Response can be partial or complete (as previously defined), whichever status is recorded first.
Time to Progression
Progression is defined as the first evaluation that shows progression (either by RECIST or WHO criteria):
Progressive Disease according to RECIST response criteria: >=20% increase in the sum of the Longest Diameter of target lesions or unequivocal progression of non-target lesions. Appearance of new lesions will also constitute progressive disease.
Progressive Disease according to WHO response criteria: Increase in size of existing lesions or appearance of new lesions.
Duration of Overall Survival
Patients were followed with regards to survival even after they left the trial (ie after End of Treatment visit). Deaths that occurred after patient participation ended were collected all the way through to the overall end of the trial which took place on Oct 31, 2009. These deaths were used to calculate overall survival.
Number of Days the Patients Were Hospitalized for Cancer-related Symptoms or Toxicity of Treatment
The cumulative sum of hospitalization days during the study, per patient. Some patients had multiple hospitalizations.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00604968
Brief Title
Pegylated Liposomal Doxorubicin (Caelyx(R)) as Monotherapy in Elderly Patients With Locally Advanced and/or Metastatic Breast Cancer (Study P05059)
Official Title
Caelyx(R) in Breast Cancer in the Elderly. Pegylated Liposomal Doxorubicin (Caelyx(R)) as Monotherapy in Elderly Patients With Locally Advanced and/or Metastatic Breast Cancer.
Study Type
Interventional
2. Study Status
Record Verification Date
May 2017
Overall Recruitment Status
Terminated
Study Start Date
February 7, 2007 (Actual)
Primary Completion Date
October 16, 2009 (Actual)
Study Completion Date
October 16, 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to evaluate the safety and efficacy of pegylated liposomal doxorubicin (Caelyx) in elderly patients who are to receive first-line chemotherapy for metastatic or locally advanced breast cancer, not amenable to surgery.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Neoplasms
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
25 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Caelyx
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Caelyx (pegylated liposomal doxorubicin; SCH 200746)
Intervention Description
Caelyx will be administered intravenously at a dose of 40 mg/m^2 on day one every 4 weeks until progression, or unacceptable toxicity, or other reason to discontinue the study treatment. The drug is diluted in 250 ml glucose 5% (500 ml for doses >=90 mg).
Primary Outcome Measure Information:
Title
Time to Treatment Failure (Defined as Progression of Disease [According to the Response Evaluation Criteria in Solid Tumors (RECIST) or World Health Organization (WHO) Criteria] or Unacceptable Toxicity Leading to Discontinuation of Treatment or Death).
Description
Treatment failure was defined as progression of disease (according to the RECIST or WHO criteria) or unacceptable toxicity leading to discontinuation of treatment or death. Progressive Disease according to RECIST response criteria: >=20% increase in the sum of the Longest Diameter of target lesions or unequivocal progression of non-target lesions. Appearance of new lesions will also constitute progressive disease. Progressive Disease according to WHO response criteria: Increase in size of existing lesions or appearance of new lesions.
Time Frame
Time of treatment until progression of disease or unacceptable toxicity leading to discontinuation of treatment or death, assessed every 12th week until end of treatment (study planned to continue until all participants ended treatment).
Secondary Outcome Measure Information:
Title
Number of Patients With Stable Disease (SD) as Best Response
Description
Response was calculated according to RECIST criteria except for bone metastasis where WHO criteria was used. For patients with skeletal disease only, WHO criteria was used. For patients with measurable disease according to RECIST as well as bone metastasis, both RECIST & WHO were used.
RECIST response criteria for SD required steady state of response of at least 9 weeks duration. There may be no appearance of new lesions.
WHO response criteria for SD required no significant change for at least 8 weeks.
Time Frame
Time of treatment until treatment discontinuation, assessed every 12th week until end of treatment (study planned to continue until all participants ended treatment).
Title
Number of Patients With Partial Response (PR) as Best Response
Description
Response was calculated according to RECIST criteria except for bone metastasis where WHO criteria was used. For patients with skeletal disease only, WHO criteria was used. For patients with measurable disease according to RECIST as well as bone metastasis, both RECIST & WHO were used.
RECIST PR criteria required >=30% decrease in certain target lesions & no increase in size of non-target lesions or appearance of new lesions
WHO PR criteria required partial decrease in size of lytic lesions, recalcification of lytic lesions, or decreased density of blastic lesions for >=4 wks
Time Frame
Time of treatment until treatment discontinuation, assessed every 12th week until end of treatment (study planned to continue until all participants ended treatment).
Title
Number of Patients With Progressive Disease (PD) as Best Response
Description
Response was calculated according to RECIST criteria except for bone metastasis where WHO criteria was used. For patients with skeletal disease only, WHO criteria was used. For patients with measurable disease according to RECIST as well as bone metastasis, both RECIST & WHO were used.
RECIST PD criteria required >=20% increase in certain target lesions OR progression of non-target lesions, or appearance of new lesions
WHO PD criteria required increase in size of existing lesions or appearance of new lesions.
Time Frame
Time of treatment until treatment discontinuation, assessed every 12th week until end of treatment (study planned to continue until all participants ended treatment).
Title
Number of Patients Requiring Dose Reduction
Description
The protocol contains instructions to reduce the Caelyx dose according to specific schedules, in cases necessary due to reasons such as hematological toxicity, non-hematological toxicity, cardiotoxicity, or other toxic side-effects of treatment reducing quality of life etc.
Time Frame
Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
Title
Time to Response
Description
Response can be partial (>=30% decrease in the sum of Longest Diameter of target lesions, determined by two observations not less than 4 weeks apart; no unequivocal increase in the size of non-target lesions or the appearance of new lesions may occur) or complete (disappearance of all clinical evidence of tumor determined by 2 observations not less than 4 weeks apart), whichever status is recorded first.
Time Frame
Time of treatment until response, assessed every 12th week until end of treatment (study planned to continue until all participants ended treatment).
Title
Duration of Response
Description
Duration of response is defined as the time span from the first evaluation that shows response until the first evaluation that shows progression. Where patients did not show progress, duration of response was measured from the first evaluation that showed response until they discontinued the study.
Response can be partial or complete (as previously defined), whichever status is recorded first.
Time Frame
Time of treatment until treatment discontinuation, assessed every 12th week until end of treatment (study planned to continue until all participants ended treatment).
Title
Time to Progression
Description
Progression is defined as the first evaluation that shows progression (either by RECIST or WHO criteria):
Progressive Disease according to RECIST response criteria: >=20% increase in the sum of the Longest Diameter of target lesions or unequivocal progression of non-target lesions. Appearance of new lesions will also constitute progressive disease.
Progressive Disease according to WHO response criteria: Increase in size of existing lesions or appearance of new lesions.
Time Frame
Time of treatment until progression, assessed every 12th week until end of treatment (study planned to continue until all participants ended treatment).
Title
Duration of Overall Survival
Description
Patients were followed with regards to survival even after they left the trial (ie after End of Treatment visit). Deaths that occurred after patient participation ended were collected all the way through to the overall end of the trial which took place on Oct 31, 2009. These deaths were used to calculate overall survival.
Time Frame
Time of treatment until death, up to the time that all participants ended treatment
Title
Number of Days the Patients Were Hospitalized for Cancer-related Symptoms or Toxicity of Treatment
Description
The cumulative sum of hospitalization days during the study, per patient. Some patients had multiple hospitalizations.
Time Frame
Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients meeting the following criteria will be eligible for enrollment.
Female patients with histologic or cytologic diagnosis of breast cancer that is locally advanced or metastatic, and not amenable to surgery.
Age >= 65 years.
World Health Organization (WHO) Performance Status 0 - 2
Measurable disease in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Patients with bone metastasis can also be included but will be evaluated according to WHO criteria. Patients with non-measurable disease can also be included.
Left ventricular ejection fraction (LVEF) >= 50% verified by ultrasound cardiography (UCG); no clinical signs of heart disease.
Normal organ function, except due to disease involvement, however maximum deviation:
S-creatinine <= 1.5 x upper normal limit;
Bilirubin <= 2 x upper normal limit;
Alanine aminotransferase (ALAT) and/or aspartate aminotransferase (ASAT) <= 3 x upper normal limit. In case of liver metastases, ALAT and/or ASAT <= 5 x upper normal limit.
Adequate bone marrow function, ie:
Platelets >= 100 x 10^9/L;
Neutrophils >= 1.5 x 10^9/L;
White Blood Cell (WBC) >= 3.0 x 10^9/L;
Hemoglobin > 90 g/L.
Life expectancy >= 12 weeks.
Patients having received oral and written information and having provided written informed consent.
Exclusion Criteria:
Patients will not be enrolled if any of the following conditions apply.
Previous chemotherapy for metastatic disease. (The patient may have received previous endocrine therapy or single-drug Herceptin. Intrapleural or intrapericardial Novantrone is allowed.)
Recurrence <= 12 months after adjuvant anthracycline-containing treatment and/or prior doxorubicin > 300 mg/m^2 or epirubicin > 540 mg/m^2.
Myocardial infarction within 6 months of planned inclusion.
Symptomatic brain metastases.
Human Epidermal growth factor Receptor 2 (HER-2) positivity eligible for treatment with trastuzumab, or estrogen receptor (ER) positivity eligible for hormonal therapy.
Allergy to anthracyclines.
Uncontrolled infection.
Other not radically treated malignancy.
Other disease or condition contraindicating treatment or not allowing follow-up.
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf
http://engagezone.msd.com/ds_documentation.php
Citations:
PubMed Identifier
22056077
Citation
Green H, Stal O, Bachmeier K, Backlund LM, Carlsson L, Hansen J, Lagerlund M, Norberg B, Franzen A, Aleskog A, Malmstrom A. Pegylated liposomal doxorubicin as first-line monotherapy in elderly women with locally advanced or metastatic breast cancer: novel treatment predictive factors identified. Cancer Lett. 2011 Dec 27;313(2):145-53. doi: 10.1016/j.canlet.2011.07.017. Epub 2011 Aug 31.
Results Reference
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Pegylated Liposomal Doxorubicin (Caelyx(R)) as Monotherapy in Elderly Patients With Locally Advanced and/or Metastatic Breast Cancer (Study P05059)
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