Combination Chemotherapy With or Without Trastuzumab in Treating Women With Metastatic Breast Cancer

NCT00004888 | Completed Phase 2 Results

• 3 other identifiers: NCI-2012-02949E3198U10CA021115
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

Brief Summary

Phase II trial to study the effectiveness of combination chemotherapy with or without trastuzumab in treating women who have metastatic breast cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.

Conditions

Recurrent Breast Cancer; Stage IV Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Grades of Cardiotoxicity Events in the Subset of Patients Reporting a Cardiotoxicity Event

  This table summarizes the cardiotoxicity events of different grades. Grade 1 is a decline of left ventricular ejection fraction(LVEF) \>=10% but \<20% of baseline value. Grade 2 is LVEF below LLN (50%) or decline of LVEF \>=20% of baseline value. Grade 3 is congestive heart failure responsive to treatment. Please note that only a subset of patients reported cardiotoxic events so the totals will not add up to the total number of participants.

  Baseline, after cycle 4 (~84 days), after cycle 8 (~168 days), and 30 or more days after last cycle of induction therapy

• Summary of Left Ventricular Ejection Fraction Values

  This table summarizes the LVEF information at baseline, post Cycle 4, post Cycle 8, and 30 or more days after Cycle 8 on all treated patients and on the eligible subset. LVEF drops reported are absolute (not relative) drops.

  Baseline, after cycle 4, after cycle 8, and 30 or more days after last cycle of induction therapy.

Secondary Outcomes (4)

• Best Overall Response Using Eastern Cooperative Group Solid Tumor Response Criteria.

  Assessed every 3 months for 2 years, then every 6 months for 3 years, then annually until death or until reaching full study stop date. Data as of Nov 21, 2007 is used for this report. Please note that best overall response is reported in the table.

• Overall Survival

  Assessed every 3 months for 2 years, then every 6 months for 3 years, then annually until death or until reaching full study stop date. Data as of November 21, 2007 is used for this report.

• Progression-Free Survival

  Assessed every 3 months for 2 years, then every 6 months for 3 years, then annually until death or until reaching full study stop date. Data as of November 21, 2007 is used for this report.

• Duration of Response

  Assessed every 3 months for 2 years, then every 6 months for 3 years, then annually until death or until reaching full study stop date. Data as of November 21, 2007 is used for this report.

Study Arms (2)

Arm I (combination chemotherapy)

EXPERIMENTAL

Patients receive doxorubicin hydrochloride liposome IV over 30 minutes followed by docetaxel IV over 1 hour. Treatment is repeated every 3 weeks for 8 courses in the absence of disease progression or unacceptable toxicity. Patients may receive maintenance therapy of docetaxel IV over 1 hour either weekly or every 3 weeks. Maintenance continues in the absence of disease progression or unacceptable toxicity.

Drug: pegylated liposomal doxorubicin hydrochloride; Drug: docetaxel; Other: laboratory biomarker analysis

Arm II (combination chemotherapy, trastuzumab)

EXPERIMENTAL

Patients receive trastuzumab IV over 90 minutes on day 1, with subsequent doses over 30 minutes. Patients receive doxorubicin HCl liposome IV over 30 minutes followed by docetaxel IV over 1 hour on day 2 of course 1, followed by subsequent doses on day 1 of each course. Antibody therapy continues weekly and chemotherapy every 3 weeks for 8 courses. Patients may receive maintenance therapy of trastuzumab IV over 30 minutes weekly followed by docetaxel IV over 1 hour weekly or every 3 weeks. Maintenance continues in the absence of disease progression or unacceptable toxicity.

Drug: pegylated liposomal doxorubicin hydrochloride; Drug: docetaxel; Biological: trastuzumab; Other: laboratory biomarker analysis

Interventions

pegylated liposomal doxorubicin hydrochloride DRUG

Given IV

Also known as: CAELYX, Dox-SL, DOXIL, doxorubicin hydrochloride liposome, LipoDox

Arm I (combination chemotherapy); Arm II (combination chemotherapy, trastuzumab)

docetaxel DRUG

Given IV

Also known as: RP 56976, Taxotere, TXT

Arm I (combination chemotherapy); Arm II (combination chemotherapy, trastuzumab)

trastuzumab BIOLOGICAL

Given IV

Also known as: anti-c-erB-2, Herceptin, MOAB HER2

Arm II (combination chemotherapy, trastuzumab)

laboratory biomarker analysis OTHER

Correlative studies

Arm I (combination chemotherapy); Arm II (combination chemotherapy, trastuzumab)

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed adenocarcinoma of the breast with manifestations of metastatic progression
• HER2 expression status in primary breast tissue and/or site(s) of metastasis must be determined by the ECOG Pathology Coordinating Office; (these are the results that will be used at time of registration); NOTE: for this protocol, HER2/neu non-overexpressed status will be defined as 0 and 1+ scores using the DAKO HercepTest; HER2 overexpressed status will be defined as 2+ score (if confirmed amplified by FISH) or 3+ score using the DAKO HercepTest
• Cytologically positive pleural or peritoneal effusions are considered evaluable disease provided local intra-cavitary treatment is not introduced at the onset of therapy; to be considered as evaluable disease, pleural effusions may not have been previously drained or sclerosed
• Blastic or mixed blastic/lytic osseous metastases only are evaluable disease provided they are accompanied by an analgesic requirement or a decrease in performance status, and will not require radiation treatment within two cycles from the start of protocol; pure osteolytic disease is evaluable; bone disease must be x-ray proven for the site to be evaluable; patients whose only evidence of metastatic disease is an abnormal bone scan without confirmatory x-rays are not eligible for this study
• No prior chemotherapy for advanced disease; prior adjuvant chemotherapy (including taxanes) allowed, if completed \> 6 months before the diagnosis of metastatic disease; no prior adjuvant anthracycline, nor any prior exposure to other anthracycline- (e.g., epirubicin, any liposomal doxorubicin formulation), nor any anthracenedione- (e.g., mitoxantrone) containing regimen allowed; no prior therapy with Herceptin allowed; NOTE: chemotherapy after ipsilateral breast recurrence following breast conservation surgery would not be considered chemotherapy for advanced disease; however, in post-mastectomy patients chemotherapy for local/regional recurrence is considered treatment for advanced disease
• No prior radiotherapy other than to the conserved breast, to the post-mastectomy chest wall, or to a limited field involving \< 25% of marrow-containing bone; NOTE: previous post-mastectomy radiation therapy involving chest wall ± internal mammary lymph node chain (IMN) is allowed; however, patients who received photon IMN treatment are ineligible; NOTE: radiotherapy must be completed \>= 2 weeks prior to registration; it may not be given concurrently with Doxil, Taxotere, or Herceptin
• Prior hormonal therapy in either a metastatic or adjuvant setting is allowed, but patients must have been off such therapy for \>= 2 weeks prior to registration
• Disease-free of prior non-breast invasive malignancies for \>= 5 years with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
• ECOG performance status of 0, 1, or 2
• At least two weeks after any major surgery (including mastectomy) and recovered from all toxicity
• Creatinine =\< 1.5 mg/dl
• Granulocytes \>= 1,500/mm³
• Platelets \>= 100,000/mm³
• SGOT(AST) =\< 2.5 x the upper limit of normal
• Bilirubin within normal limits for institution

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Eastern Cooperative Oncology Group

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

liposomal doxorubicin; Docetaxel; Trastuzumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Study Statistician
• Organization: Eastern Cooperative Oncology Group Statistical Office

617-632-3012

Study Officials

• Antonio Wolff

  Eastern Cooperative Oncology Group

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: March 7, 2000
• First Posted: January 27, 2003
• Study Start: January 1, 2001
• Primary Completion: April 1, 2008
• Study Completion: May 1, 2009
• Last Updated: May 23, 2014
• Results First Posted: November 23, 2011

Record last verified: 2012-12

Locations

US (1)