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

NCT00580112 | Completed Phase 2

• 2 other identifiers: CR014764ET-B-027-06
• Study Type: interventional
• Target: 127
• Locations: 4 countries
• Sites: 33

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.

Conditions

Breast Neoplasms

Keywords

Breast Neoplasms; Trabectedin; Yondelis

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With Confirmed Objective Response (OR) by Independent External Review (IER)

  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.

  Baseline up to progressive disease or death, assessed every 6 weeks (up to 90 weeks)

• Percentage of Participants With Confirmed Objective Response (OR) by Investigators' Assessment

  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.

  Baseline up to progressive disease or death, assessed every 6 weeks (up to 90 weeks)

Secondary Outcomes (6)

• 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 (DR) by Investigators' Assessment

  Baseline up to progressive disease or death, assessed every 6 weeks (up to 90 weeks)

• Progression-Free Survival (PFS) by Independent Expert Review (IER)

  Baseline up to progressive disease or death, assessed every 6 weeks (up to 90 weeks)

• Progression-Free Survival (PFS) by Investigators' Assessment

  Baseline up to progressive disease or death, assessed every 6 weeks (up to 90 weeks)

• Number of Participants With Changes in Tumor Volume

  Baseline up to progressive disease or death, assessed every 6 weeks (up to 90 weeks)

Other Outcomes (1)

• Number of Participants With Adverse Events

  Baseline up to 30 days after last dose of study drug

Study Arms (3)

Group A

EXPERIMENTAL

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; Drug: Trabectedin

Group B

EXPERIMENTAL

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

Group C

EXPERIMENTAL

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

Interventions

Dexamethasone DRUG

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.

Group A; Group B; Group C

Trabectedin DRUG

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.

Also known as: Yondelis

Group A; Group B; Group C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Johnson & Johnson Pharmaceutical Research & Development, L.L.C.: lead
• PharmaMar: collaborator

Study Sites (33)

Unknown Facility

Sedona, Arizona, United States

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Denver, Colorado, United States

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Torrington, Connecticut, United States

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Indianapolis, Indiana, United States

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Westminster, Maryland, United States

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Minneapolis, Minnesota, United States

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Columbia, Missouri, United States

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Kansas City, Missouri, United States

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St Louis, Missouri, United States

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Amsterdam, New York, United States

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New York, New York, United States

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Bedford, Texas, United States

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Dallas, Texas, United States

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Houston, Texas, United States

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San Antonio, Texas, United States

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Tyler, Texas, United States

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Norfolk, Virginia, United States

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Salem, Virginia, United States

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Seattle, Washington, United States

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Spokane, Washington, United States

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Yakima, Washington, United States

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Bourdeaux, France

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Marseille, France

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Saint-Herblain, France

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Strasbourg, France

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Villejuif, France

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Jerusalem, Israel

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Rehovot, Israel

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Tel Aviv, Israel

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Tel Litwinsky, Israel

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Lubin, Poland

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Rybnik, Poland

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Szczecin, Poland

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Related Publications (1)

• Delaloge S, Wolp-Diniz R, Byrski T, Blum JL, Goncalves A, Campone M, Lardelli P, Kahatt C, Nieto A, Cullell-Young M, Lubinski J. Activity of trabectedin in germline BRCA1/2-mutated metastatic breast cancer: results of an international first-in-class phase II study. Ann Oncol. 2014 Jun;25(6):1152-8. doi: 10.1093/annonc/mdu134. Epub 2014 Apr 1.

  PMID: 24692579 DERIVED

Related Links

• 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

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Dexamethasone; Trabectedin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Dioxoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrahydroisoquinolines; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial

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

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2007
• First Posted: December 24, 2007
• Study Start: June 1, 2007
• Primary Completion: August 1, 2011
• Study Completion: August 1, 2011
• Last Updated: February 25, 2014

Record last verified: 2014-02

Locations

US (21); FR (5); PL (3); IL (4)