Pegylated Liposomal Doxorubicin (Caelyx(R)) as Monotherapy in Elderly Patients With Locally Advanced and/or Metastatic Breast Cancer (Study P05059)

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.

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.

Study Overview

• Status: Terminated
• Conditions: Breast Neoplasms
• Intervention / Treatment: Drug: Caelyx (pegylated liposomal doxorubicin; SCH 200746)

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Caelyx	Drug: Caelyx (pegylated liposomal doxorubicin; SCH 200746); 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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 Measures

Outcome Measure	Measure Description	Time Frame
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.	Time of treatment until treatment discontinuation, assessed every 12th week until end of treatment (study planned to continue until all participants ended treatment).
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	Time of treatment until treatment discontinuation, assessed every 12th week until end of treatment (study planned to continue until all participants ended treatment).
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.	Time of treatment until treatment discontinuation, assessed every 12th week until end of treatment (study planned to continue until all participants ended treatment).
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 of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
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.	Time of treatment until response, assessed every 12th week until end of treatment (study planned to continue until all participants ended treatment).
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 of treatment until treatment discontinuation, assessed every 12th week until end of treatment (study planned to continue until all participants ended treatment).
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.	Time of treatment until progression, assessed every 12th week until end of treatment (study planned to continue until all participants ended treatment).
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.	Time of treatment until death, up to the time that all participants ended treatment
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.	Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 7, 2007
• Primary Completion (ACTUAL): October 16, 2009
• Study Completion (ACTUAL): October 16, 2009

Study Registration Dates

• First Submitted: January 21, 2008
• First Submitted That Met QC Criteria: January 29, 2008
• First Posted (ESTIMATE): January 30, 2008

Study Record Updates

• Last Update Posted (ACTUAL): June 7, 2017
• Last Update Submitted That Met QC Criteria: May 15, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Doxorubicin; Liposomal doxorubicin
• Other Study ID Numbers: P05059

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD 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