An Efficacy Study of Trabectedin in the Treatment of Participants With Specific Subtypes of Metastatic Breast Cancer

Sponsor

Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (Industry)

Overall Status

Completed

CT.gov ID

NCT00580112

Collaborator

PharmaMar (Industry)

127

Enrollment

Locations

Arms

Duration (Months)

3.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the effectiveness and safety of trabectedin in 3 subpopulations of participants with previously treated progressive metastatic ( spread of a cancer from one organ or part to another non-adjacent organ or part) breast cancer (abnormal tissue that grows and spreads in the body until it kills) participants.

Condition or Disease	Intervention/Treatment	Phase
Breast Neoplasms	Drug: Dexamethasone Drug: Trabectedin	Phase 2

Detailed Description

This is an open-label (all people know the identity of the intervention), prospective (study following participants forward in time), multi-center (when more than 1 hospital or medical school team work on a medical research study) study evaluating the effectiveness and safety of trabectedin in 3 subpopulations of breast cancer participants: Group A: triple negative profile for estrogen receptor, progesterone receptor and human estrogen receptor, Group B: human epidermal growth factor receptor-2 overexpressing tumors (HER-2+) and Group C: familial breast cancer gene 1 (BRCA1) or breast cancer gene 2 (BRCA2) mutation carrier. Participants will receive trabectedin 1.3 milligram per square meter (mg/m^2) intravenous infusion (a fluid or a medicine delivered into a vein by way of a needle) over 3-hour every 3 weeks, on Day 1 of each cycle. Each cycle length will be 3 weeks. Treatment will be continued until disease progression, unmanageable toxicity, participant refusal or treatment delay no longer than 3 weeks due to toxicity. Efficacy will be primarily evaluated by percentage of participants with confirmed objective response by independent external review and Investigators assessment. Participants' safety will be monitored throughout the study.

Study Design

Study Type:

Interventional

Actual Enrollment :

127 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase II, Multicenter, Open-label, Clinical Trial of Trabectedin (Yondelis) in Metastatic Breast Cancer Patients With Triple Negative Profile (ER-, PR-, HER2-), HER2 Overexpressing Tumors and BRCA1 or BRCA2 Mutation Carriers

Study Start Date :

Jun 1, 2007

Actual Primary Completion Date :

Aug 1, 2011

Actual Study Completion Date :

Aug 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group A Participants with triple negative phenotype: estrogen receptor, progesterone receptor and human estrogen receptor-2 (HER-2) negative status for breast cancer (abnormal tissue that grows and spreads in the body until it kills) will receive trabectedin 1.3 milligram per meter square (mg/m^2) intravenous infusion (a fluid or a medicine delivered into a vein by way of a needle) over 3-hours (hrs) every 3 weeks, on Day 1 of each cycle. Each cycle length will be 3 weeks. Treatment will be continued until disease progression, unmanageable toxicity, participant refusal or treatment delay no longer than 3 weeks due to toxicity. Along with study drug participants will be given dexamethasone 4 milligram (mg) orally 24 hrs and 12hrs before study drug infusion on Day -1, followed by dexamethasone 20 mg intravenously 30 minutes before study drug infusion on Day 1, followed by dexamethasone 4 mg orally 24, 36, 48, 60 and 72hrs after the start of study drug infusion from Day 1 to 3.	Drug: Dexamethasone Dexamethasone 4 mg orally 24 hrs and 12 hrs before study drug infusion on Day -1, followed by dexamethasone 20 mg intravenously 30 minutes before study drug infusion on Day 1, followed by dexamethasone 4 mg orally 24, 36, 48, 60 and 72 hrs after the start of study drug infusion on Day 1 to 3. Drug: Trabectedin Trabectedin 1.3 mg/m^2 intravenous infusion over 3-hrs every 3 weeks, on Day 1 of each cycle. Each cycle length will be 3 weeks. Other Names: Yondelis
Experimental: Group B Participants with overexpressing HER-2 breast cancer will receive trabectedin 1.3 mg/m^2 intravenous infusion over 3-hrs every 3 weeks, on Day 1 of each cycle. Each cycle length will be 3 weeks. Treatment will be continued until disease progression, unmanageable toxicity, participant refusal or treatment delay no longer than 3 weeks due to toxicity. Along with study drug participants will be given dexamethasone 4 milligram (mg) orally 24 hrs and 12hrs before study drug infusion on Day -1, followed by dexamethasone 20 mg intravenously 30 minutes before study drug infusion on Day 1, followed by dexamethasone 4 mg orally 24, 36, 48, 60 and 72 hrs after the start of study drug infusion from Day 1 to 3.	Drug: Dexamethasone Dexamethasone 4 mg orally 24 hrs and 12 hrs before study drug infusion on Day -1, followed by dexamethasone 20 mg intravenously 30 minutes before study drug infusion on Day 1, followed by dexamethasone 4 mg orally 24, 36, 48, 60 and 72 hrs after the start of study drug infusion on Day 1 to 3. Drug: Trabectedin Trabectedin 1.3 mg/m^2 intravenous infusion over 3-hrs every 3 weeks, on Day 1 of each cycle. Each cycle length will be 3 weeks. Other Names: Yondelis
Experimental: Group C Participants with familial breast cancer gene 1 (BRCA1) or breast cancer gene 2 (BRCA2) mutation carriers cancer will receive trabectedin 1.3 mg/m^2 intravenous infusion over 3-hrs every 3 weeks on Day 1 of each cycle. Each cycle length will be 3 weeks. Treatment will be continued until disease progression, unmanageable toxicity, participant refusal or treatment delay no longer than 3 weeks due to toxicity. Along with study drug participants will be given dexamethasone 4 mg orally 24 hrs and 12hrs before study drug infusion on Day -1, followed by dexamethasone 20 mg intravenously 30 minutes before study drug infusion on Day 1, followed by dexamethasone 4 mg orally 24, 36, 48, 60 and 72 hrs after the start of study drug infusion from Day 1 to 3.	Drug: Dexamethasone Dexamethasone 4 mg orally 24 hrs and 12 hrs before study drug infusion on Day -1, followed by dexamethasone 20 mg intravenously 30 minutes before study drug infusion on Day 1, followed by dexamethasone 4 mg orally 24, 36, 48, 60 and 72 hrs after the start of study drug infusion on Day 1 to 3. Drug: Trabectedin Trabectedin 1.3 mg/m^2 intravenous infusion over 3-hrs every 3 weeks, on Day 1 of each cycle. Each cycle length will be 3 weeks. Other Names: Yondelis

Arm

Intervention/Treatment

Experimental: Group A

Participants with triple negative phenotype: estrogen receptor, progesterone receptor and human estrogen receptor-2 (HER-2) negative status for breast cancer (abnormal tissue that grows and spreads in the body until it kills) will receive trabectedin 1.3 milligram per meter square (mg/m^2) intravenous infusion (a fluid or a medicine delivered into a vein by way of a needle) over 3-hours (hrs) every 3 weeks, on Day 1 of each cycle. Each cycle length will be 3 weeks. Treatment will be continued until disease progression, unmanageable toxicity, participant refusal or treatment delay no longer than 3 weeks due to toxicity. Along with study drug participants will be given dexamethasone 4 milligram (mg) orally 24 hrs and 12hrs before study drug infusion on Day -1, followed by dexamethasone 20 mg intravenously 30 minutes before study drug infusion on Day 1, followed by dexamethasone 4 mg orally 24, 36, 48, 60 and 72hrs after the start of study drug infusion from Day 1 to 3.

Drug: Dexamethasone

Dexamethasone 4 mg orally 24 hrs and 12 hrs before study drug infusion on Day -1, followed by dexamethasone 20 mg intravenously 30 minutes before study drug infusion on Day 1, followed by dexamethasone 4 mg orally 24, 36, 48, 60 and 72 hrs after the start of study drug infusion on Day 1 to 3.

Drug: Trabectedin

Trabectedin 1.3 mg/m^2 intravenous infusion over 3-hrs every 3 weeks, on Day 1 of each cycle. Each cycle length will be 3 weeks.

Other Names:

Yondelis

Experimental: Group B

Participants with overexpressing HER-2 breast cancer will receive trabectedin 1.3 mg/m^2 intravenous infusion over 3-hrs every 3 weeks, on Day 1 of each cycle. Each cycle length will be 3 weeks. Treatment will be continued until disease progression, unmanageable toxicity, participant refusal or treatment delay no longer than 3 weeks due to toxicity. Along with study drug participants will be given dexamethasone 4 milligram (mg) orally 24 hrs and 12hrs before study drug infusion on Day -1, followed by dexamethasone 20 mg intravenously 30 minutes before study drug infusion on Day 1, followed by dexamethasone 4 mg orally 24, 36, 48, 60 and 72 hrs after the start of study drug infusion from Day 1 to 3.

Drug: Dexamethasone

Drug: Trabectedin

Trabectedin 1.3 mg/m^2 intravenous infusion over 3-hrs every 3 weeks, on Day 1 of each cycle. Each cycle length will be 3 weeks.

Other Names:

Yondelis

Experimental: Group C

Participants with familial breast cancer gene 1 (BRCA1) or breast cancer gene 2 (BRCA2) mutation carriers cancer will receive trabectedin 1.3 mg/m^2 intravenous infusion over 3-hrs every 3 weeks on Day 1 of each cycle. Each cycle length will be 3 weeks. Treatment will be continued until disease progression, unmanageable toxicity, participant refusal or treatment delay no longer than 3 weeks due to toxicity. Along with study drug participants will be given dexamethasone 4 mg orally 24 hrs and 12hrs before study drug infusion on Day -1, followed by dexamethasone 20 mg intravenously 30 minutes before study drug infusion on Day 1, followed by dexamethasone 4 mg orally 24, 36, 48, 60 and 72 hrs after the start of study drug infusion from Day 1 to 3.

Drug: Dexamethasone

Drug: Trabectedin

Trabectedin 1.3 mg/m^2 intravenous infusion over 3-hrs every 3 weeks, on Day 1 of each cycle. Each cycle length will be 3 weeks.

Other Names:

Yondelis

Outcome Measures

Primary Outcome Measures

Percentage of Participants With Confirmed Objective Response (OR) by Independent External Review (IER) [Baseline up to progressive disease or death, assessed every 6 weeks (up to 90 weeks)]
Percentage of participants with confirmed objective response will be based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. CR is defined as disappearance of all target lesions. PR is those with at least 30 percent decrease in the sum of longest dimensions of target lesions taking as a reference baseline sum longest dimensions. IER will be done to re-examine all Investigator assessed outcomes.
Percentage of Participants With Confirmed Objective Response (OR) by Investigators' Assessment [Baseline up to progressive disease or death, assessed every 6 weeks (up to 90 weeks)]
Percentage of participants with objective response based assessment of confirmed CR or confirmed PR according to RECIST. Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. The CR is defined as disappearance of all target lesions. The PR is those with at least 30 percent decrease in the sum of longest dimensions of target lesions taking as a reference baseline sum longest dimensions.

Secondary Outcome Measures

Duration of Response (DR) by Independent Expert Review (IER) [Baseline up to progressive disease or death, assessed every 6 weeks (up to 90 weeks)]
Duration of Response is considered as time in months from the first documentation of objective tumor response to objective tumor progression or death due to any cause. Duration of tumor response was calculated as: (the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that will be subsequently confirmed plus 1) divided by 30.44. DR will be calculated for the subgroup of participants with a confirmed objective tumor response. IER will be done to re-examine all Investigator assessed outcomes and to provide an independent assessment of response and progression date.
Duration of Response (DR) by Investigators' Assessment [Baseline up to progressive disease or death, assessed every 6 weeks (up to 90 weeks)]
Duration of Response is considered as time in months from the first documentation of objective tumor response to objective tumor progression or death due to any cause. Duration of tumor response is calculated as: (the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that will be subsequently confirmed plus 1) divided by 30.44. The DR will be calculated for the subgroup of participants with a confirmed objective tumor response.
Progression-Free Survival (PFS) by Independent Expert Review (IER) [Baseline up to progressive disease or death, assessed every 6 weeks (up to 90 weeks)]
PFS is defined as the time in months from start of study treatment to first documentation of objective tumor progression or death due to any cause whichever comes first. PFS is calculated as (first event date minus the date of first dose of study medication plus 1) divided by 30.44. Tumor progression will be determined from radiological image (where data meet the criteria for progressive disease [PD]). IER will be done to re-examine all Investigator assessed outcomes and to provide an independent assessment of response and progression date.
Progression-Free Survival (PFS) by Investigators' Assessment [Baseline up to progressive disease or death, assessed every 6 weeks (up to 90 weeks)]
PFS is defined as the time in months from start of study treatment to first documentation of objective tumor progression or death due to any cause whichever comes first. PFS is calculated as (first event date minus the date of first dose of study medication plus 1) divided by 30.44. Tumor progression will be determined from radiological image (where data meet the criteria for progressive disease [PD]). IER will be done to re-examine all Investigator assessed outcomes and to provide an independent assessment of response and progression date.
Number of Participants With Changes in Tumor Volume [Baseline up to progressive disease or death, assessed every 6 weeks (up to 90 weeks)]
Three dimensional analysis will be used to measure changes in tumor volume.
Number of Participants With Changes in Tumoral Radiological Density [Baseline up to progressive disease or death, assessed every 6 weeks (up to 90 weeks)]
Three dimensional analysis will be used to measure changes in tumoral radiological density.

Other Outcome Measures

Number of Participants With Adverse Events [Baseline up to 30 days after last dose of study drug]
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Participants with histologically proven diagnosis of progressive metastatic breast cancer
Participants with measurable disease as per the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines
Participants with bone metastases currently receiving bisphosphonates for palliation will be eligible if other sites of measurable disease are present
Participants with Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1 and adequately recovered from the acute toxicity of any prior treatment
Participants with serum creatinine less than or equal to 1.5 milligram per deciliter (mg/dl) or creatinine clearance greater than or equal to 30 milliliter per minute (ml/min)

Exclusion Criteria:

Participants with previous exposure to trabectedin
Participants with more than 3 previous chemotherapy regimens for metastatic disease and known hypersensitivity to components of trabectedin intravenous formulation or dexamethasone
Pregnant or lactating women or any women of childbearing potential who is not employing adequate contraception
Completion of previous therapy : Less than 2 weeks from radiation therapy or last dose of hormonal therapy, less than 3 weeks from previous biological therapy or chemotherapy
Participants with known leptomeningeal disease and other serious illnesses like congestive heart failure or angina pectoris; myocardial infarction within 1 year before enrolment; uncontrolled arterial hypertension or arrhythmias or active infection or psychiatric disorder or active viral hepatitis

Contacts and Locations

Locations

	City	State	Country
1	Sedona	Arizona	United States
2	Denver	Colorado	United States
3	Torrington	Connecticut	United States
4	Indianapolis	Indiana	United States
5	Westminster	Maryland	United States
6	Minneapolis	Minnesota	United States
7	Columbia	Missouri	United States
8	Kansas City	Missouri	United States
9	St. Louis	Missouri	United States
10	Amsterdam	New York	United States
11	New York	New York	United States
12	Bedford	Texas	United States
13	Dallas	Texas	United States
14	Houston	Texas	United States
15	San Antonio	Texas	United States
16	Tyler	Texas	United States
17	Norfolk	Virginia	United States
18	Salem	Virginia	United States
19	Seattle	Washington	United States
20	Spokane	Washington	United States
21	Yakima	Washington	United States
22	Bourdeaux		France
23	Marseille		France
24	Saint Herblain		France
25	Strasbourg Cedex		France
26	Villejuif		France
27	Jerusalem		Israel
28	Rehovot		Israel
29	Tel Hashomer		Israel
30	Tel-Aviv		Israel
31	Lubin		Poland
32	Rybnik		Poland
33	Szczecin		Poland

Sponsors and Collaborators

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
PharmaMar

Investigators

Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial, Johnson & Johnson Pharmaceutical Research & Development, L.L.C.