Caelyx, Cyclophosphamide and Herceptin in Patients With Metastatic Breast Cancer

• Sponsor: Spanish Breast Cancer Research Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00258960
• Collaborator: Schering-Plough (Industry)
• Enrollment: 49
• Locations: 12
• Arm: 1
• Actual Duration (Months): 40.9
• Patients Per Site: 4.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Eligible patients must receive Caelyx plus Cyclophosphamide plus Herceptin for 6 cycles that will be administered every 4 weeks.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Liposomal Doxorubicin; Drug: Cyclophosphamide; Drug: Trastuzumab	Phase 2

Detailed Description

Sample size calculation will be done by means of Simon's method in 2 stages for phase II studies and will be based on the principal aim of the study (evaluation of the rate of objective response).

The hypothesis brings over of the efficiency of the treatment it will be accepted if a rate of objective response of at least 55 % is obtained, rejecting the efficiency of the treatment when the rate of response targets be lower than 35 %. In this case, considering an alpha error of 0.05 and 80 % power, 14 patients will be included in the first stage; the study would continue if more than 5 objective responses were found. The total number of patients to including in the study would be 44. The results will be significant if they find at least 20 objective responses.

Assuming a drop-out rate of 10 %, the total number of patients needed is 49 patients.

Study Design

• Study Type: Interventional
• Actual Enrollment: 49 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase IV/II Trial With the Combination of Pegylated Liposomal Doxorubicin (Caelyx), Cyclophosphamide and Trastuzumab in Patients With Metastatic Breast Cancer With Overexpression of Human Epidermal Growth Factor Receptor 2 (HER2)/Neu
• Actual Study Start Date: Feb 15, 2006
• Actual Primary Completion Date: Jul 1, 2008
• Actual Study Completion Date: Jul 14, 2009

Arms and Interventions

Arm	Intervention/Treatment
Other: Caelyx,Cyclophosphamide,Trastuzumab Caelyx (Liposomal Doxorubicin) 50 mg/m2 every 4 weeks for 6 cycles, Cyclophosphamide 600 mg/m2 every 4 weeks for 6 cycles, Trastuzumab weekly for 24 weeks, at dose of 2mg/kg (day 1 loading dose of 4mg/kg)	Drug: Liposomal Doxorubicin; Other Names: Caelyx ; Drug: Cyclophosphamide; Other Names: Cytoxan ; Drug: Trastuzumab; Other Names: Herceptin

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate (ORR) [Up to cycle 6 (24 weeks)]

   ORR is the sum of the Complete Responses (CR) and Partial Responses (PR) according to the RECIST criteria, experienced for each patient during treatment (recorded from the start of the treatment until disease progression). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT scan (computed tomography) or MRI (magnetic resonance imaging): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response Rate (ORR) = CR + PR.

Secondary Outcome Measures

1. Time to Progression (TTP) [Through study treatment, and follow up period, assessed up to 88 weeks]

   TTP was defined as the time elapsed from first treatment until clinical evidence of disease progression. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

2. Time to Treatment Failure (TTF) [Through study treatment, and follow up period, assessed up to 88 weeks]

   TTF was defined as the time elapsed from first treatment until patient discontinuation due to toxicity, disease progression, death or withdrawal of consent for any reason, whichever occurred first.

3. Response Duration [Through study treatment, and follow up period, assessed up to 88 weeks]

   Response duration was defined as the time elapsed from the first evidence of tumor response (Complete response or Partial Response) until clinical evidence of disease progression or death occurred.

4. Overall Survival (OS) [Through study treatment, and follow up period, assessed up to 88 weeks]

   OS was defined as the time elapsed from first treatment until death from any cause.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients must sign an informed consent before of specific procedures of clinical trial.

• Patients with histologically confirmed breast cancer and overexpression of Her2neu.

• Age> 18 years.

• Eastern Cooperative Oncology Group (ECOG) equal or < 2.

• Patients have not been treated previously with chemotherapy for metastatic disease.

• Patients must have at least one measurable lesion according to RECIST criteria.

• Patients should have an adequate organ function to tolerate chemotherapy.

Exclusion Criteria:

• Patients with hypersensitivity reactions to any of the medications of the clinical trial.

• Patients who are pregnant or lactating are not eligible.

• Hepatic disease.

• Not controlled active infection

• Symptomatic metastatic brain cancer

• Previous adjuvant treatment with anthracyclines with a total accumulated dose > 300 mg/m2 (Doxorubicin) or > 600 mg/m2 (Epirubicin)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Germans Trias i Pujol	Badalona	Barcelona	Spain	08916
2	Fundación Hospital Alcorcón	Alcorcón	MAdrid	Spain	28922
3	Hospital Clinic i Provincial	Barcelona		Spain	08036
4	Hospital Puerta del Mar	Cadiz		Spain	11009
5	Hospital Provincial de Castellón	Castelló		Spain	12002
6	Complejo Hospitalario de Jaen	Jaén		Spain	23007
7	Hospital Juan Canalejo	La Coruña		Spain	15006
8	Centro Oncológico Regional de Galicia	La Coruña		Spain	15009
9	Hospital Xeral Calde de Lugo	Lugo		Spain	27004
10	Hospital Universitario Doce de Octubre	MAdrid		Spain	28021
11	Hospital Clínico Universitario San Carlos	MAdrid		Spain	28040
12	Hospital Nuestra Señora de Candelaria	Santa Cruz De Tenerife		Spain	38010

Sponsors and Collaborators

• Spanish Breast Cancer Research Group
• Schering-Plough

Investigators

• Study Director: Study Director, Hospital Clínico Universitario San Carlos

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Spanish Breast Cancer Research Group (GEICAM) is a Spanish Breast Cancer Research Group

Publications

None provided.

• Responsible Party: Spanish Breast Cancer Research Group
• ClinicalTrials.gov Identifier: NCT00258960
• Other Study ID Numbers: GEICAM/2004-05
• First Posted: Nov 28, 2005
• Last Update Posted: Jul 15, 2019
• Last Verified: Apr 1, 2019

• Keywords provided by Spanish Breast Cancer Research Group: HER2 positive breast cancer; Metastatic breast cancer
• Additional relevant MeSH terms: Breast Neoplasms; Cyclophosphamide; Doxorubicin; Liposomal doxorubicin; Trastuzumab

Study Results

Participant Flow

Recruitment Details	Between February 2006 and June 2008, 49 patients were enrolled at 12 Spanish sites. One patient never received treatment due to early death from progressive disease and was not included in this analysis.

Arm/Group Title	Liposomal Doxorubicin,Cyclophosphamide,Trastuzumab
Arm/Group Description	Liposomal Doxorubicin 50 mg/m2 every 4 weeks for six cycles, Cyclophosphamide 600 mg/m2 every 4 weeks for six cycles, Trastuzumab weekly for 24 weeks, at dose of 2mg/kg (day 1 loading dose of 4mg/kg) Liposomal Doxorubicin Cyclophosphamide Trastuzumab
Period Title: Overall Study
STARTED	49
COMPLETED	32
NOT COMPLETED	17

Baseline Characteristics

Arm/Group Title	Liposomal Doxorubicin,Cyclophosphamide,Trastuzumab
Arm/Group Description	Liposomal Doxorubicin 50 mg/m2 every 4 weeks for six cycles, Cyclophosphamide 600 mg/m2 every 4 weeks for six cycles, Trastuzumab weekly for 24 weeks, at dose of 2mg/kg (day 1 loading dose of 4mg/kg) Liposomal Doxorubicin Cyclophosphamide Trastuzumab
Overall Participants	48
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	57
Sex: Female, Male (Count of Participants)
Female	48 100%
Male	0 0%
Eastern Cooperative Oncology Group (ECOG) (Count of Participants)
ECOG 0	26 54.2%
ECOG 1	20 41.7%
ECOG 2	2 4.2%
Menopausal Status (Count of Participants)
Premenopausal	9 18.8%
Postmenopausal	39 81.3%
Hormonal receptor status (Count of Participants)
Positive	24 50%
Negative	24 50%
Disease stage at diagnosis (Count of Participants)
Stage I to III	26 54.2%
Stage IV	22 45.8%
Prior neo(adjuvant) chemotherapy (Count of Participants)
Prior neo(adjuvant) chemotherapy	23 47.9%
Non Prior neo(adjuvant) chemotherapy	25 52.1%
Number of disease sites (Count of Participants)
1 disease site	10 20.8%
2 disease sites	18 37.5%
3 disease sites or more	20 41.7%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (ORR)
Description	ORR is the sum of the Complete Responses (CR) and Partial Responses (PR) according to the RECIST criteria, experienced for each patient during treatment (recorded from the start of the treatment until disease progression). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT scan (computed tomography) or MRI (magnetic resonance imaging): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response Rate (ORR) = CR + PR.
Time Frame	Up to cycle 6 (24 weeks)

Outcome Measure Data

Analysis Population Description

49 patients included but 1 is not considered due to not receive any treatment and died before start

Arm/Group Title	Caelyx,Cyclophosphamide,Trastuzumab
Arm/Group Description	Caelyx (Liposomal Doxorubicin) 50 mg/m2 every 4 weeks for 6 cycles, Cyclophosphamide 600 mg/m2 every 4 weeks for 6 cycles, Trastuzumab weekly for 24 weeks, at dose of 2mg/kg (day 1 loading dose of 4mg/kg) Liposomal Doxorubicin Cyclophosphamide Trastuzumab
Measure Participants	48
Count of Participants [Participants]	33 68.8%

2. Secondary Outcome

Title	Time to Progression (TTP)
Description	TTP was defined as the time elapsed from first treatment until clinical evidence of disease progression. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time Frame	Through study treatment, and follow up period, assessed up to 88 weeks

Outcome Measure Data

Analysis Population Description

49 patients included but 1 is not considered due to not receive any treatment and died before start

Arm/Group Title	Caelyx,Cyclophosphamide,Trastuzumab
Arm/Group Description	Caelyx (Liposomal Doxorubicin) 50 mg/m2 every 4 weeks for 6 cycles, Cyclophosphamide 600 mg/m2 every 4 weeks for 6 cycles, Trastuzumab weekly for 24 weeks, at dose of 2mg/kg (day 1 loading dose of 4mg/kg) Liposomal Doxorubicin Cyclophosphamide Trastuzumab
Measure Participants	48
Median (95% Confidence Interval) [Months]	12

3. Secondary Outcome

Title	Time to Treatment Failure (TTF)
Description	TTF was defined as the time elapsed from first treatment until patient discontinuation due to toxicity, disease progression, death or withdrawal of consent for any reason, whichever occurred first.
Time Frame	Through study treatment, and follow up period, assessed up to 88 weeks

Outcome Measure Data

Analysis Population Description

49 patients included but 1 is not considered due to not receive any treatment and died before start

Arm/Group Title	Caelyx,Cyclophosphamide,Trastuzumab
Arm/Group Description	Caelyx (Liposomal Doxorubicin) 50 mg/m2 every 4 weeks for 6 cycles, Cyclophosphamide 600 mg/m2 every 4 weeks for 6 cycles, Trastuzumab weekly for 24 weeks, at dose of 2mg/kg (day 1 loading dose of 4mg/kg) Liposomal Doxorubicin Cyclophosphamide Trastuzumab
Measure Participants	48
Median (95% Confidence Interval) [Months]	9.7

4. Secondary Outcome

Title	Response Duration
Description	Response duration was defined as the time elapsed from the first evidence of tumor response (Complete response or Partial Response) until clinical evidence of disease progression or death occurred.
Time Frame	Through study treatment, and follow up period, assessed up to 88 weeks

Outcome Measure Data

Analysis Population Description

Patients with Overall Response (see ORR objective)

Arm/Group Title	Caelyx,Cyclophosphamide,Trastuzumab
Arm/Group Description	Caelyx (Liposomal Doxorubicin) 50 mg/m2 every 4 weeks for 6 cycles, Cyclophosphamide 600 mg/m2 every 4 weeks for 6 cycles, Trastuzumab weekly for 24 weeks, at dose of 2mg/kg (day 1 loading dose of 4mg/kg) Liposomal Doxorubicin Cyclophosphamide Trastuzumab
Measure Participants	33
Median (95% Confidence Interval) [Months]	9.51

5. Secondary Outcome

Title	Overall Survival (OS)
Description	OS was defined as the time elapsed from first treatment until death from any cause.
Time Frame	Through study treatment, and follow up period, assessed up to 88 weeks

Outcome Measure Data

Analysis Population Description

49 patients included but 1 is not considered due to not receive any treatment and died before start

Arm/Group Title	Caelyx,Cyclophosphamide,Trastuzumab
Arm/Group Description	Caelyx (Liposomal Doxorubicin) 50 mg/m2 every 4 weeks for 6 cycles, Cyclophosphamide 600 mg/m2 every 4 weeks for 6 cycles, Trastuzumab weekly for 24 weeks, at dose of 2mg/kg (day 1 loading dose of 4mg/kg) Liposomal Doxorubicin Cyclophosphamide Trastuzumab
Measure Participants	48
Median (95% Confidence Interval) [Months]	34.2

Adverse Events

Time Frame	Through study treatment up to 30 days after last study dose, up to 84 weeks
Adverse Event Reporting Description	49 patients included but 1 is not considered due to not receive any treatment and died before start
Arm/Group Title	Liposomal Doxorubicin,Cyclophosphamide,Trastuzumab
Arm/Group Description	Liposomal Doxorubicin 50 mg/m2 every 4 weeks for six cycles, Cyclophosphamide 600 mg/m2 every 4 weeks for six cycles, Trastuzumab weekly for 24 weeks, at dose of 2mg/kg (day 1 loading dose of 4mg/kg)
All Cause Mortality
	Liposomal Doxorubicin,Cyclophosphamide,Trastuzumab
	Affected / at Risk (%)	# Events
Total	2/48 (4.2%)
Serious Adverse Events
	Liposomal Doxorubicin,Cyclophosphamide,Trastuzumab
	Affected / at Risk (%)	# Events
Total	16/48 (33.3%)
Blood and lymphatic system disorders
Febrile neutropenia grade 3	3/48 (6.3%)
Neutropenia grade 3	1/48 (2.1%)
General disorders
Holocraneal cephalea	1/48 (2.1%)
Hypersensibility reaction grade 3	2/48 (4.2%)
Palmoplantar erythrodysesthesia grade 3, stomatitis grade 3	1/48 (2.1%)
Neutropenia grade 4, fever grade 1, oral mucositis grade 3	1/48 (2.1%)
Infections and infestations
Catheter - related infection grade 3	1/48 (2.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Progression disease	1/48 (2.1%)
Nervous system disorders
Cerebrovascular ischemia	1/48 (2.1%)
Hemorrhage CNS grade 5	1/48 (2.1%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory insufficiency	1/48 (2.1%)
Skin and subcutaneous tissue disorders
Infection with normal ANC (skin celluties grade 3)	1/48 (2.1%)
Vascular disorders
Hemorrhage subarachnoid	1/48 (2.1%)
Other (Not Including Serious) Adverse Events
	Liposomal Doxorubicin,Cyclophosphamide,Trastuzumab
	Affected / at Risk (%)	# Events
Total	48/48 (100%)
Blood and lymphatic system disorders
Leukocytes	1/48 (2.1%)
Neutrophils / Granulocytes	5/48 (10.4%)
Leukocytes	9/48 (18.8%)
Leukocytes	10/48 (20.8%)
Hemoglobin	10/48 (20.8%)
Lymphopenia	9/48 (18.8%)
Lymphopenia	7/48 (14.6%)
Neutrophils / Granulocytes	5/48 (10.4%)
Neutrophils / Granulocytes	9/48 (18.8%)
Hemoglobin	27/48 (56.3%)
Leukocytes	14/48 (29.2%)
Cardiac disorders
Left Ventricular systolic dysfunction	8/48 (16.7%)
Left Ventricular diastolic dysfunction	19/48 (39.6%)
Gastrointestinal disorders
Mucositis / Stomatitis	1/48 (2.1%)
Mucositis / Stomatitis	10/48 (20.8%)
Heartburn/dyspepsia	20/48 (41.7%)
Anorexia	8/48 (16.7%)
Mucositis / Stomatitis	9/48 (18.8%)
Nausea	16/48 (33.3%)
General disorders
Fatigue	1/48 (2.1%)
Fatigue	16/48 (33.3%)
Fatigue	12/48 (25%)
Fever	9/48 (18.8%)
Infections and infestations
Infection with normal ANC or G1 or 2 neutrophils	10/48 (20.8%)
Metabolism and nutrition disorders
Alkaline phosphatase	10/48 (20.8%)
ALT, SGPT	20/48 (41.7%)
AST, SGOT	18/48 (37.5%)
Reproductive system and breast disorders
Pneumonitis/Pulmonary infiltrates	1/48 (2.1%)
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)	2/48 (4.2%)
Cough	8/48 (16.7%)
Skin and subcutaneous tissue disorders
Rash: Hand-foot skin reaction	14/48 (29.2%)
Rash/desquamation	11/48 (22.9%)
Rash/desquamation	8/48 (16.7%)
Rash: Hand-foot skin reaction	10/48 (20.8%)
Rash: Hand-foot skin reaction	13/48 (27.1%)
Hair loss/alopecia	12/48 (25%)
Hyperpigmentation	8/48 (16.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.