Trial Outcomes & Findings for Pegylated Liposomal Doxorubicin (Caelyx(R)) as Monotherapy in Elderly Patients With Locally Advanced and/or Metastatic Breast Cancer (Study P05059) (NCT NCT00604968)

NCT ID: NCT00604968

Last Updated: 2017-06-07

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE4

Target enrollment

25 participants

Primary outcome timeframe

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).

Results posted on

2017-06-07

Participant Flow

28 patients were screened and 25 were enrolled. All 25 patients enrolled received \>=1 cycle of treatment with Caelyx. Per protocol, treatment was to continue until progression, unacceptable toxicity, or other reason for discontinuation of treatment - all subjects eventually discontinued treatment but were considered to have completed the study.

Participant milestones

Participant milestones
Measure
Caelyx
Caelyx was 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 was diluted in 250 ml glucose 5% (500 ml for doses \>=90 mg).
Overall Study
STARTED
25
Overall Study
COMPLETED
25
Overall Study
NOT COMPLETED
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Caelyx
n=25 Participants
Caelyx was 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 was diluted in 250 ml glucose 5% (500 ml for doses \>=90 mg).
Age, Categorical
<=18 years
0 Participants
n=93 Participants
Age, Categorical
Between 18 and 65 years
0 Participants
n=93 Participants
Age, Categorical
>=65 years
25 Participants
n=93 Participants
Age, Continuous
72.3 years
STANDARD_DEVIATION 5.0 • n=93 Participants
Sex: Female, Male
Female
25 Participants
n=93 Participants
Sex: Female, Male
Male
0 Participants
n=93 Participants

PRIMARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure
Caelyx
n=25 Participants
Caelyx was 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 was diluted in 250 ml glucose 5% (500 ml for doses \>=90 mg).
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).
5.52 Months
Interval 3.67 to 8.52

SECONDARY outcome

Timeframe: Time of treatment until treatment discontinuation, assessed every 12th week until end of treatment (study planned to continue until all participants ended treatment).

Population: 10 patients were followed by RECIST, 4 patients were followed by WHO Response criteria, and 8 patients by both RECIST and WHO Response criteria (n=22). 3 patients had non-measurable disease and could not be included in the analysis.

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.

Outcome measures

Outcome measures
Measure
Caelyx
n=22 Participants
Caelyx was 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 was diluted in 250 ml glucose 5% (500 ml for doses \>=90 mg).
Number of Patients With Stable Disease (SD) as Best Response
Patients followed by RECIST & WHO (n=8)
4 participants
Number of Patients With Stable Disease (SD) as Best Response
Patients followed by RECIST only (n=10)
5 participants
Number of Patients With Stable Disease (SD) as Best Response
Patients followed by WHO only (n=4)
4 participants

SECONDARY outcome

Timeframe: Time of treatment until treatment discontinuation, assessed every 12th week until end of treatment (study planned to continue until all participants ended treatment).

Population: 10 patients were followed by RECIST, 4 patients were followed by WHO Response criteria, and 8 patients by both RECIST and WHO Response criteria (n=22). 3 patients had non-measurable disease and could not be included in the analysis.

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

Outcome measures

Outcome measures
Measure
Caelyx
n=22 Participants
Caelyx was 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 was diluted in 250 ml glucose 5% (500 ml for doses \>=90 mg).
Number of Patients With Partial Response (PR) as Best Response
Patients followed by RECIST only (n=10)
1 participants
Number of Patients With Partial Response (PR) as Best Response
Patients followed by WHO only (n=4)
0 participants
Number of Patients With Partial Response (PR) as Best Response
Patients followed by RECIST & WHO (n=8)
2 participants

SECONDARY outcome

Timeframe: Time of treatment until treatment discontinuation, assessed every 12th week until end of treatment (study planned to continue until all participants ended treatment).

Population: 10 patients were followed by RECIST, 4 patients were followed by WHO Response criteria, and 8 patients by both RECIST and WHO Response criteria (n=22). 3 patients had non-measurable disease and could not be included in the analysis.

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.

Outcome measures

Outcome measures
Measure
Caelyx
n=22 Participants
Caelyx was 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 was diluted in 250 ml glucose 5% (500 ml for doses \>=90 mg).
Number of Patients With Progressive Disease (PD) as Best Response
Patients followed by RECIST only (n=10)
4 participants
Number of Patients With Progressive Disease (PD) as Best Response
Patients followed by WHO only (n=4)
0 participants
Number of Patients With Progressive Disease (PD) as Best Response
Patients followed by RECIST & WHO (n=8)
2 participants

SECONDARY outcome

Timeframe: Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).

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.

Outcome measures

Outcome measures
Measure
Caelyx
n=25 Participants
Caelyx was 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 was diluted in 250 ml glucose 5% (500 ml for doses \>=90 mg).
Number of Patients Requiring Dose Reduction
Due to weight change
6 participants
Number of Patients Requiring Dose Reduction
Due to toxicity/adverse event
4 participants

SECONDARY outcome

Timeframe: Time of treatment until response, assessed every 12th week until end of treatment (study planned to continue until all participants ended treatment).

Population: Only 3 patients had measureable 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.

Outcome measures

Outcome measures
Measure
Caelyx
n=3 Participants
Caelyx was 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 was diluted in 250 ml glucose 5% (500 ml for doses \>=90 mg).
Time to Response
Patient 1
12.2 Weeks
Interval 12.2 to 12.2
Time to Response
Patient 2
11.4 Weeks
Interval 11.4 to 11.4
Time to Response
Patient 3
12.0 Weeks
Interval 12.0 to 12.0

SECONDARY outcome

Timeframe: Time of treatment until treatment discontinuation, assessed every 12th week until end of treatment (study planned to continue until all participants ended treatment).

Population: Three patients showed Partial Response according to RECIST criteria.

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.

Outcome measures

Outcome measures
Measure
Caelyx
n=3 Participants
Caelyx was 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 was diluted in 250 ml glucose 5% (500 ml for doses \>=90 mg).
Duration of Response
Patient 1
11.8 weeks
Interval 11.8 to 11.8
Duration of Response
Patient 2
48.6 weeks
Interval 48.6 to 48.6
Duration of Response
Patient 3
17.8 weeks
Interval 17.8 to 17.8

SECONDARY outcome

Timeframe: Time of treatment until progression, assessed every 12th week until end of treatment (study planned to continue until all participants ended treatment).

Population: Of the 25 patients in the study 3 patients had non-measurable disease and could not be included in the progression analysis.

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.

Outcome measures

Outcome measures
Measure
Caelyx
n=22 Participants
Caelyx was 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 was diluted in 250 ml glucose 5% (500 ml for doses \>=90 mg).
Time to Progression
5.69 months
Interval 3.74 to 13.8

SECONDARY outcome

Timeframe: Time of treatment until death, up to the time that all participants ended treatment

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.

Outcome measures

Outcome measures
Measure
Caelyx
n=25 Participants
Caelyx was 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 was diluted in 250 ml glucose 5% (500 ml for doses \>=90 mg).
Duration of Overall Survival
20.6 months
Interval 6.58 to 25.6

SECONDARY outcome

Timeframe: Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).

Population: Of the 25 total patients, 12 were hospitalized during the study.

The cumulative sum of hospitalization days during the study, per patient. Some patients had multiple hospitalizations.

Outcome measures

Outcome measures
Measure
Caelyx
n=12 Participants
Caelyx was 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 was diluted in 250 ml glucose 5% (500 ml for doses \>=90 mg).
Number of Days the Patients Were Hospitalized for Cancer-related Symptoms or Toxicity of Treatment
Patient 1
1 days
Number of Days the Patients Were Hospitalized for Cancer-related Symptoms or Toxicity of Treatment
Patient 2
1 days
Number of Days the Patients Were Hospitalized for Cancer-related Symptoms or Toxicity of Treatment
Patient 3
6 days
Number of Days the Patients Were Hospitalized for Cancer-related Symptoms or Toxicity of Treatment
Patient 4
4 days
Number of Days the Patients Were Hospitalized for Cancer-related Symptoms or Toxicity of Treatment
Patient 5
5 days
Number of Days the Patients Were Hospitalized for Cancer-related Symptoms or Toxicity of Treatment
Patient 6
71 days
Number of Days the Patients Were Hospitalized for Cancer-related Symptoms or Toxicity of Treatment
Patient 7
16 days
Number of Days the Patients Were Hospitalized for Cancer-related Symptoms or Toxicity of Treatment
Patient 8
1 days
Number of Days the Patients Were Hospitalized for Cancer-related Symptoms or Toxicity of Treatment
Patient 9
1 days
Number of Days the Patients Were Hospitalized for Cancer-related Symptoms or Toxicity of Treatment
Patient 10
3 days
Number of Days the Patients Were Hospitalized for Cancer-related Symptoms or Toxicity of Treatment
Patient 11
33 days
Number of Days the Patients Were Hospitalized for Cancer-related Symptoms or Toxicity of Treatment
Patient 12
20 days

Adverse Events

Caelyx

Serious events: 9 serious events
Other events: 25 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Caelyx
n=25 participants at risk
Caelyx was 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 was diluted in 250 ml glucose 5% (500 ml for doses \>=90 mg).
Cardiac disorders
MYOCARDIAL INFARCTION
4.0%
1/25 • Number of events 1 • Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
Gastrointestinal disorders
ABDOMINAL PAIN
4.0%
1/25 • Number of events 1 • Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
Gastrointestinal disorders
DYSPEPSIA
4.0%
1/25 • Number of events 1 • Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
Gastrointestinal disorders
VOMITING
4.0%
1/25 • Number of events 1 • Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
General disorders
PYREXIA
8.0%
2/25 • Number of events 2 • Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
Infections and infestations
CENTRAL LINE INFECTION
4.0%
1/25 • Number of events 1 • Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
Infections and infestations
CLOSTRIDIAL INFECTION
4.0%
1/25 • Number of events 1 • Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
Infections and infestations
CYSTITIS
4.0%
1/25 • Number of events 1 • Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
Infections and infestations
PNEUMONIA
4.0%
1/25 • Number of events 1 • Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
Infections and infestations
URINARY TRACT INFECTION
8.0%
2/25 • Number of events 2 • Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
Metabolism and nutrition disorders
HYPOGLYCAEMIA
4.0%
1/25 • Number of events 1 • Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
Respiratory, thoracic and mediastinal disorders
PULMONARY EMBOLISM
4.0%
1/25 • Number of events 1 • Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).

Other adverse events

Other adverse events
Measure
Caelyx
n=25 participants at risk
Caelyx was 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 was diluted in 250 ml glucose 5% (500 ml for doses \>=90 mg).
Blood and lymphatic system disorders
ANAEMIA
16.0%
4/25 • Number of events 5 • Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
Blood and lymphatic system disorders
NEUTROPENIA
16.0%
4/25 • Number of events 7 • Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
Eye disorders
DRY EYE
8.0%
2/25 • Number of events 2 • Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
Eye disorders
LACRIMATION INCREASED
8.0%
2/25 • Number of events 2 • Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
Gastrointestinal disorders
ABDOMINAL PAIN
12.0%
3/25 • Number of events 6 • Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
Gastrointestinal disorders
CONSTIPATION
24.0%
6/25 • Number of events 7 • Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
Gastrointestinal disorders
DIARRHOEA
24.0%
6/25 • Number of events 9 • Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
Gastrointestinal disorders
FLATULENCE
8.0%
2/25 • Number of events 2 • Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
Gastrointestinal disorders
GASTRITIS
8.0%
2/25 • Number of events 2 • Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
Gastrointestinal disorders
NAUSEA
64.0%
16/25 • Number of events 31 • Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
Gastrointestinal disorders
STOMATITIS
24.0%
6/25 • Number of events 15 • Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
Gastrointestinal disorders
VOMITING
28.0%
7/25 • Number of events 12 • Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
General disorders
CHEST PAIN
12.0%
3/25 • Number of events 4 • Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
General disorders
FATIGUE
68.0%
17/25 • Number of events 21 • Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
General disorders
OEDEMA PERIPHERAL
16.0%
4/25 • Number of events 5 • Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
General disorders
PYREXIA
24.0%
6/25 • Number of events 11 • Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
Investigations
BLOOD ALKALINE PHOSPHATASE INCREASED
8.0%
2/25 • Number of events 2 • Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
Investigations
BLOOD LACTATE DEHYDROGENASE INCREASED
12.0%
3/25 • Number of events 3 • Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
Investigations
C-REACTIVE PROTEIN INCREASED
8.0%
2/25 • Number of events 4 • Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
Investigations
HAEMOGLOBIN DECREASED
8.0%
2/25 • Number of events 2 • Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
Investigations
WEIGHT DECREASED
12.0%
3/25 • Number of events 3 • Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
Metabolism and nutrition disorders
DECREASED APPETITE
36.0%
9/25 • Number of events 9 • Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
Musculoskeletal and connective tissue disorders
ARTHRALGIA
8.0%
2/25 • Number of events 2 • Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
Musculoskeletal and connective tissue disorders
BACK PAIN
24.0%
6/25 • Number of events 9 • Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL PAIN
16.0%
4/25 • Number of events 4 • Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
Nervous system disorders
DIZZINESS
8.0%
2/25 • Number of events 2 • Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
Nervous system disorders
HEADACHE
16.0%
4/25 • Number of events 4 • Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
Respiratory, thoracic and mediastinal disorders
COUGH
12.0%
3/25 • Number of events 4 • Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
Skin and subcutaneous tissue disorders
ALOPECIA
24.0%
6/25 • Number of events 6 • Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
Skin and subcutaneous tissue disorders
BLISTER
16.0%
4/25 • Number of events 4 • Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
Skin and subcutaneous tissue disorders
DRY SKIN
8.0%
2/25 • Number of events 2 • Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
Skin and subcutaneous tissue disorders
ERYTHEMA
8.0%
2/25 • Number of events 3 • Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
Skin and subcutaneous tissue disorders
PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME
52.0%
13/25 • Number of events 18 • Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).
Skin and subcutaneous tissue disorders
RASH
16.0%
4/25 • Number of events 8 • Time of treatment until treatment discontinuation (study planned to continue until all participants ended treatment).

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Results disclosure agreements

  • Principal investigator is a sponsor employee If an investigator wishes to publish data from the study, a copy must be provided to the sponsor for review at least 60 days before submission for publication. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days. If issues arise regarding scientific integrity or regulatory compliance, the sponsor will review these issues with the investigator. The sponsor will not change scientific content or suppress information.
  • Publication restrictions are in place

Restriction type: OTHER