Doxorubicin HCI Liposome Injection Versus Weekly Docetaxel in Patients First Relapse Metastatic Breast Cancer

• Sponsor: SCRI Development Innovations, LLC (Other)
• Overall Status: Completed
• CT.gov ID: NCT00193037
• Collaborator: Ortho Biotech, Inc. (Industry), Aventis Pharmaceuticals (Industry)
• Enrollment: 102
• Location: 1
• Arms: 2
• Duration (Months): 105
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

The efficacy of single agent liposomal doxorubicin as compared to single agent docetaxel will be evaluated as first line treatment in metastatic breast cancer patients, with subsequent crossover to the opposite arm at disease progression or patient intolerance. We will explore this as well as any possible cross resistance between these two agents.

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

Detailed Description

Upon determination of eligibility, patients will be randomly assigned to one of two treatment arms:

• Liposomal Doxorubicin

• Docetaxel

For ever 2 patients treated, 1 will receive treatment A (Liposomal Doxorubicin) and 1 will receive treatment B (Docetaxel). Patients demonstrating progression on either ARM will be eligible for cross over to treatment in the other ARM, provided patient still meets the eligibility laboratory and performance status criteria. The study is not blinded so both the patient and the doctor will know which treatment has been assigned.

Study Design

• Study Type: Interventional
• Actual Enrollment: 102 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Randomized Crossover Study Doxorubicin HCI Liposome Injection Versus Weekly Docetaxel in Patients First Relapse Metastatic Breast Cancer
• Study Start Date: Feb 1, 2001
• Actual Primary Completion Date: Dec 1, 2008
• Actual Study Completion Date: Nov 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Liposomal Doxorubicin Liposomal doxorubicin 40 mg/m2 by 1 hour IV infusion repeated every 28 days.	Drug: Liposomal Doxorubicin; Liposomal Doxorubicin; Other Names: Doxil
Experimental: Docetaxel Weekly docetaxel 36 mg/m2 by 30 minute IV infusion on days 1, 8, and 15 of the 28 day cycle	Drug: Docetaxel; Docetaxel; Other Names: Taxotere

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment [18 Months]

   ORR is defined as the percentage of patients who exhibit a Complete Response (CR) or Partial Response (PR). Complete Response is the total disappearance of clinically and radiologically detectable disease for at least 4 weeks. Partial Response is at least a 50% reduction of all measurable lesions as measured by the product of the perpendicular diameters of the greatest dimensions of tumor size, with no new lesions appearing for at least four weeks.

Secondary Outcome Measures

1. Progression Free Survival (PFS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Worsening of Their Disease. [18 Months]

   PFS was defined as the interval from first study treatment until the date that the first progression of breast cancer was documented, or death occurred.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

To be included in this study, you must meet the following criteria:

• Metastatic breast cancer confirmed by biopsy

• Prior adjuvant/neoadjuvant treatment allowed

• Measurable disease

• Able to perform activities of daily living with minimal assistance

• Age 18 years or older

• Adequate bone marrow, liver and kidney function

• Normal heart function

• Written informed consent

Exclusion Criteria:

You cannot participate in this study if any of the following apply to you:

• Pre-existing moderate peripheral neuropathy

• History of significant heart disease

• Meningeal metastases.

• Prior chemotherapy for metastatic breast cancer

• No measurable disease (including bone only, pleural effusions, etc.)

• Receiving Herceptin therapy.

• Women who are pregnant or lactating.

Please note: There are additional inclusion/exclusion criteria. The study center will determine if you meet all of the criteria. If you do not qualify for the trial, study personnel will explain the reasons. If you do qualify, study personnel will explain the trial in detail and answer any questions you may have.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Tennessee Oncology	Nashville	Tennessee	United States	37203

Sponsors and Collaborators

• SCRI Development Innovations, LLC
• Ortho Biotech, Inc.
• Aventis Pharmaceuticals

Investigators

• Principal Investigator: Denise A. Yardley, MD, SCRI Development Innovations, LLC

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Published article in Clinical Breast Cancer

Publications

None provided.

• Responsible Party: SCRI Development Innovations, LLC
• ClinicalTrials.gov Identifier: NCT00193037
• Other Study ID Numbers: SCRI BRE 43
• First Posted: Sep 19, 2005
• Last Update Posted: Jul 31, 2013
• Last Verified: Jul 1, 2013

• Keywords provided by SCRI Development Innovations, LLC: Breast Cancer
• Additional relevant MeSH terms: Breast Neoplasms; Docetaxel; Doxorubicin; Liposomal doxorubicin

Study Results

Participant Flow

Arm/Group Title	Arm A -Liposomal Doxorubicin Then Docetaxel	Arm B - Docetaxel Then Liposomal Doxorubicin
Arm/Group Description	Liposomal doxorubicin (Arm A) Liposomal doxorubicin 40 mg/m2 IV day 1 over one hour, repeated q 28 days thru peripheral vein or central venous access. This will define one cycle. Patients demonstrating progression on Liposomal Doxorubicin were eligible for cross over to treatment on Docetaxel, provided patient still met the eligibility laboratory and performance status criteria.	Weekly docetaxel 36 mg/m2 IV over 30 minutes on days 1, 8 and 15 followed by one week rest, administered on a q 28 day cycle. This dosing schedule will define one cycle. Patients demonstrating progression on Docetaxel were eligible for cross over to treatment on Liposomal Doxorubicin, provided patient still met the eligibility laboratory and performance status criteria.
Period Title: Randomized Treatment
STARTED	50	52
COMPLETED	32	24
NOT COMPLETED	18	28
Period Title: Randomized Treatment
STARTED	32	24
COMPLETED	32	24
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Arm A -Liposomal Doxorubicin Then Docetaxel	Arm B - Docetaxel Then Liposomal Doxorubicin	Total
Arm/Group Description	Liposomal doxorubicin (Arm A) Liposomal doxorubicin 40 mg/m2 IV day 1 over one hour, repeated q 28 days thru peripheral vein or central venous access. This will define one cycle. Patients demonstrating progression on Liposomal Doxorubicin were eligible for cross over to treatment on Docetaxel, provided the patient still met the eligibility laboratory and performance status criteria.	Weekly docetaxel 36 mg/m2 IV over 30 minutes on days 1, 8 and 15 followed by one week rest, administered on a q 28 day cycle. This dosing schedule will define one cycle. Patients demonstrating progression on Docetaxel were eligible for cross over to treatment on Liposomal Doxorubicin, provided the patient still met the eligibility laboratory and performance status criteria.	Total of all reporting groups
Overall Participants	50	52	102
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	62	62	62
Sex: Female, Male (Count of Participants)
Female	50 100%	52 100%	102 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	50 100%	52 100%	102 100%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment
Description	ORR is defined as the percentage of patients who exhibit a Complete Response (CR) or Partial Response (PR). Complete Response is the total disappearance of clinically and radiologically detectable disease for at least 4 weeks. Partial Response is at least a 50% reduction of all measurable lesions as measured by the product of the perpendicular diameters of the greatest dimensions of tumor size, with no new lesions appearing for at least four weeks.
Time Frame	18 Months

Outcome Measure Data

Analysis Population Description

Patients who were removed from treatment before evaluation were not included in analysis

Arm/Group Title	Arm A -Liposomal Doxorubicin Then Docetaxel	Arm B - Docetaxel Then Liposomal Doxorubicin
Arm/Group Description	Liposomal doxorubicin (Arm A) Liposomal doxorubicin 40 mg/m2 IV day 1 over one hour, repeated q 28 days thru peripheral vein or central venous access. This will define one cycle. Patients demonstrating progression on Liposomal Doxorubicin were eligible for cross over to treatment on Docetaxel, provided the patient still met the eligibility laboratory and performance status criteria.	Weekly docetaxel 36 mg/m2 IV over 30 minutes on days 1, 8 and 15 followed by one week rest, administered on a q 28 day cycle. This dosing schedule will define one cycle. Patients demonstrating progression on Docetaxel were eligible for cross over to treatment on Liposomal Doxorubicin, provided the patient still met the eligibility laboratory and performance status criteria.
Measure Participants	42	44
Number (95% Confidence Interval) [percentage of patients]	28	31

2. Secondary Outcome

Title	Progression Free Survival (PFS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Worsening of Their Disease.
Description	PFS was defined as the interval from first study treatment until the date that the first progression of breast cancer was documented, or death occurred.
Time Frame	18 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A -Liposomal Doxorubicin Then Docetaxel	Arm B - Docetaxel Then Liposomal Doxorubicin
Arm/Group Description	Liposomal doxorubicin (Arm A) Liposomal doxorubicin 40 mg/m2 IV day 1 over one hour, repeated q 28 days thru peripheral vein or central venous access. This will define one cycle. Patients demonstrating progression on Liposomal Doxorubicin were eligible for cross over to treatment on Docetaxel, provided the patient still met the eligibility laboratory and performance status criteria.	Weekly docetaxel 36 mg/m2 IV over 30 minutes on days 1, 8 and 15 followed by one week rest, administered on a q 28 day cycle. This dosing schedule will define one cycle. Patients demonstrating progression on Docetaxel were eligible for cross over to treatment on Liposomal Doxorubicin, provided the patient still met the eligibility laboratory and performance status criteria.
Measure Participants	48	44
Median (95% Confidence Interval) [months]	6.5	5.5

Adverse Events

Arm/Group Title	Arm A - Liposomal Doxorubicin Then Docetaxel		Arm B - Docetaxel Then Liposomal Doxorubicin
Arm/Group Description	Liposomal doxorubicin 40 mg/m2 IV day 1 over one hour, repeated q28 days thru peripheral vein or central venous access. This will define one cycle. Patients demonstrating progression on Liposomal Doxorubicin were eligible for crossover to treatment on Docetaxel, provided patient still met the eligibility lab and performance status criteria.		Weekly docetaxel 36 mg/m2 IV over 30 minutes on days 1, 8, and 15 followed by one week rest, administered on an every 28 day cycle. This dosing schedule will define one cycle. Patients demonstrating progression on Docetaxel were eligible for cross over to treatment on Liposomal Doxorubicin, provided patient still met the eligibility laboratory and performance status criteria.
All Cause Mortality
	Arm A - Liposomal Doxorubicin Then Docetaxel		Arm B - Docetaxel Then Liposomal Doxorubicin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm A - Liposomal Doxorubicin Then Docetaxel		Arm B - Docetaxel Then Liposomal Doxorubicin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/50 (36%)		22/52 (42.3%)
Cardiac disorders
Hypotension	0/50 (0%)	0	1/52 (1.9%)	1
Bradycardia	0/50 (0%)	0	1/52 (1.9%)	1
Cardiac Arrest	1/50 (2%)	1	0/52 (0%)	0
Gastrointestinal disorders
Diarrhea	2/50 (4%)	2	0/52 (0%)	0
Pain - Abdominal	1/50 (2%)	1	0/52 (0%)	0
Hemorrhage - GI	1/50 (2%)	1	1/52 (1.9%)	1
Vomiting	0/50 (0%)	0	1/52 (1.9%)	1
Nausea	0/50 (0%)	0	1/52 (1.9%)	1
Dehydration	0/50 (0%)	0	1/52 (1.9%)	1
Diverticular Abscess	1/50 (2%)	1	0/52 (0%)	0
General disorders
Failure to Thrive	1/50 (2%)	1	0/52 (0%)	0
Fever	0/50 (0%)	0	1/52 (1.9%)	1
Hepatobiliary disorders
Liver Dysfunction	1/50 (2%)	1	1/52 (1.9%)	1
Infections and infestations
Febrile Neutropenia	0/50 (0%)	0	1/52 (1.9%)	1
Metabolism and nutrition disorders
Hypoglycemia	1/50 (2%)	1	0/52 (0%)	0
Hyperglycemia	1/50 (2%)	1	0/52 (0%)	0
Hypokalemia	0/50 (0%)	0	1/52 (1.9%)	1
Musculoskeletal and connective tissue disorders
Pain - Bone	1/50 (2%)	1	0/52 (0%)	0
Fracture	1/50 (2%)	1	0/52 (0%)	0
Pain - Musculoskeletal	0/50 (0%)	0	1/52 (1.9%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Progressive Disease	4/50 (8%)	4	5/52 (9.6%)	5
Nervous system disorders
Syncope	0/50 (0%)	0	1/52 (1.9%)	1
CNS Ischemia	1/50 (2%)	1	0/52 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pleural Effusion	1/50 (2%)	1	0/52 (0%)	0
Dyspnea	0/50 (0%)	0	2/52 (3.8%)	2
Pneumothorax	0/50 (0%)	0	1/52 (1.9%)	1
Vascular disorders
Thrombosis/Thrombus/Embolism	0/50 (0%)	0	1/52 (1.9%)	1
Superior Vena Cava Syndome	0/50 (0%)	0	1/52 (1.9%)	1
Other (Not Including Serious) Adverse Events
	Arm A - Liposomal Doxorubicin Then Docetaxel		Arm B - Docetaxel Then Liposomal Doxorubicin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/50 (42%)		35/52 (67.3%)
Blood and lymphatic system disorders
Neutrophils	5/50 (10%)	5	1/52 (1.9%)	1
Edema	0/50 (0%)	0	4/52 (7.7%)	4
Cardiac disorders
Hypotension	0/50 (0%)	0	3/52 (5.8%)	3
Gastrointestinal disorders
Mucositis/Stomatitis	4/50 (8%)	4	3/52 (5.8%)	3
Nausea/Vomiting	2/50 (4%)	2	6/52 (11.5%)	6
General disorders
Fatigue	3/50 (6%)	3	13/52 (25%)	13
Musculoskeletal and connective tissue disorders
Arthralgia/Myalgia	2/50 (4%)	2	5/52 (9.6%)	5
Skin and subcutaneous tissue disorders
Hand-Foot	5/50 (10%)	5	0/52 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The sponsor can review/embargo results communications prior to public release for a period that is >60 days but ≤180 days from date submitted to sponsor, who may require changes to the communication in order to remove specifically identified confidential information (other than study data) and/or delay the proposed publication to enable the sponsor to seek patent protection for inventions. The PI may not publish its results until 18 mos. after the trial has been completed at all sites.