NCT00047255

Brief Summary

RATIONALE: 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. It is not yet known if docetaxel and trastuzumab are more effective with or without carboplatin in treating women who have HER2-positive breast cancer. PURPOSE: Randomized phase III trial to study the effectiveness of combining docetaxel and trastuzumab with or without carboplatin in treating women who have HER2-positive stage IIIB or stage IV breast cancer.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
263

participants targeted

Target at P25-P50 for phase_3 breast-cancer

Timeline
Completed

Started May 2002

Typical duration for phase_3 breast-cancer

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 1, 2002

Completed
5 months until next milestone

First Submitted

Initial submission to the registry

October 3, 2002

Completed
4 months until next milestone

First Posted

Study publicly available on registry

January 27, 2003

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2006

Completed
4.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2010

Completed
Last Updated

August 3, 2020

Status Verified

February 1, 2016

Enrollment Period

3.7 years

First QC Date

October 3, 2002

Last Update Submit

July 30, 2020

Conditions

Breast Cancer

Keywords

stage IIIB breast cancerstage IIIC breast cancerstage IV breast cancerrecurrent breast cancer

Outcome Measures

Primary Outcomes (1)

  • Evaluate time to disease progression after treatment with either Herceptin in with single-agent docetaxel (TH) or Herceptin with Carboplatin and TH in metastatic breast cancer pts previously untreated with chemo whose cancer contains the HER2 gene amp.

    till disease progression

Secondary Outcomes (6)

  • To compare response rate, duration of overall response, overall survival.

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  • To evaluate and compare the rate of clinical benefit, defined as CR, PR, or stable disease > 24 weeks.

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  • To compare toxicity between the 2 arms.

    2 years

  • To evaluate pathologic and molecular markers for predicting efficacy.

    2 years

  • Correlate peripheral levels of shed HER2 extracellular domain (ECD) with FISH results and to determine whether peripheral levels of shed HER2 ECD consitute a prognostic and/or predicitive factor vis-a-vis time to progression and survival.

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  • +1 more secondary outcomes

Study Arms (2)

Herceptin plus docetaxel

EXPERIMENTAL

Cycle 1: Day 1: Herceptin (H) 4 mg/kg loading dose administered by IV infusion over 90 minutes, Day 2: Docetaxel (T) 100 mg/m2 by IV infusion over 30 minutes, Day 8: (H) 2mg/kg administered by IV infusion over 30 minutes, Day 15: 2mg/kg administered by IV infusion over 30 minutes. Subsequent cycles: Day 1: (T) 100mg/m2 as 1 hour IV infusion given every 3 weeks, followed by (H) 2 mg/kg IV infusion over 30 minutes, Day 8: (H) 2 mg/kg administered by IV infusion over 30 minutes, Day 15: (H) 2 mg/kg administered by IV infusion over 30 minutes. Last cycle: Day 1: (T) 100mg/m2 as 1 hour IV infusion followed by (H) 2 mg/kg IV infusion over 30 minutes, Day 8: (H) 2 mg/kg administered by IV infusion over 30 minutes, Day 15: (H) 2 mg/kg administered by IV infusion over 30 minutes, Day 22: (H) 6 mg/kg administered by IV infusion over 30 minutes.

Drug: docetaxelBiological: trastuxumab

Docetaxel, Carboplatin, and Herceptin

EXPERIMENTAL

Cycle 1: Day 1: Herceptin (H) 4 mg/kg loading dose admin by IV over 90 mins, Day 2: Docetaxel (T) 75 mg/m2 by IV over 1 hour followed by carboplatin (C) at target AUC=6 mg/mL/min admin by IV over 30-60 mins, Day 8: (H) 2mg/kg admin by IV over 30 mins, Day 15: 2mg/kg admin by IV over 30 mins. Subsequent cycles: Day 1: (T) 75mg/m2 as 1 hour IV followed by (C) at target AUC=6 mg/mL/min admin by IV 30-60 mins every 3 weeks followed by (H) 2 mg/kg IV over 30 mins, Day 8: (H) 2 mg/kg admin by IV over 30 mins, Day 15: (H) 2 mg/kg admin by IV over 30 mins. Last cycle: Day 1: (T) 75mg/m2 as 1 hour IV followed by (C) at target AUC=6 mg/mL/min admin by IV 30-60 mins every 3 weeks followed by (H) 2 mg/kg IV over 30 mins, Day 8: (H) 2 mg/kg admin by IV over 30 mins, Day 15: (H) 2 mg/kg admin by IV over 30 mins, Day 22: (H) 6 mg/kg admin by IV over 30 mins.

Biological: trastuzumabDrug: carboplatinDrug: Docetaxel

Interventions

trastuzumabBIOLOGICAL

Cycle 1: Day 1: Herceptin (H) 4 mg/kg loading dose admin by IV over 90 mins, Day 2: Docetaxel (T) 75 mg/m2 by IV over 1 hour followed by carboplatin (C) at target AUC=6 mg/mL/min admin by IV over 30-60 mins, Day 8: (H) 2mg/kg admin by IV over 30 mins, Day 15: 2mg/kg admin by IV over 30 mins. Subsequent cycles: Day 1: (T) 75mg/m2 as 1 hour IV followed by (C) at target AUC=6 mg/mL/min admin by IV 30-60 mins every 3 weeks followed by (H) 2 mg/kg IV over 30 mins, Day 8: (H) 2 mg/kg admin by IV over 30 mins, Day 15: (H) 2 mg/kg admin by IV over 30 mins. Last cycle: Day 1: (T) 75mg/m2 as 1 hour IV followed by (C) at target AUC=6 mg/mL/min admin by IV 30-60 mins every 3 weeks followed by (H) 2 mg/kg IV over 30 mins, Day 8: (H) 2 mg/kg admin by IV over 30 mins, Day 15: (H) 2 mg/kg admin by IV over 30 mins, Day 22: (H) 6 mg/kg admin by IV over 30 mins.

Also known as: herceptin
Docetaxel, Carboplatin, and Herceptin
carboplatinDRUG

Cycle 1: Day 1: Herceptin (H) 4 mg/kg loading dose admin by IV over 90 mins, Day 2: Docetaxel (T) 75 mg/m2 by IV over 1 hour followed by carboplatin (C) at target AUC=6 mg/mL/min admin by IV over 30-60 mins, Day 8: (H) 2mg/kg admin by IV over 30 mins, Day 15: 2mg/kg admin by IV over 30 mins. Subsequent cycles: Day 1: (T) 75mg/m2 as 1 hour IV followed by (C) at target AUC=6 mg/mL/min admin by IV 30-60 mins every 3 weeks followed by (H) 2 mg/kg IV over 30 mins, Day 8: (H) 2 mg/kg admin by IV over 30 mins, Day 15: (H) 2 mg/kg admin by IV over 30 mins. Last cycle: Day 1: (T) 75mg/m2 as 1 hour IV followed by (C) at target AUC=6 mg/mL/min admin by IV 30-60 mins every 3 weeks followed by (H) 2 mg/kg IV over 30 mins, Day 8: (H) 2 mg/kg admin by IV over 30 mins, Day 15: (H) 2 mg/kg admin by IV over 30 mins, Day 22: (H) 6 mg/kg admin by IV over 30 mins.

Docetaxel, Carboplatin, and Herceptin
DocetaxelDRUG

Cycle 1: Day 1: Herceptin (H) 4 mg/kg loading dose administered by IV infusion over 90 minutes, Day 2: Docetaxel (T) 100 mg/m2 by IV infusion over 30 minutes, Day 8: (H) 2mg/kg administered by IV infusion over 30 minutes, Day 15: 2mg/kg administered by IV infusion over 30 minutes. Subsequent cycles: Day 1: (T) 100mg/m2 as 1 hour IV infusion given every 3 weeks, followed by (H) 2 mg/kg IV infusion over 30 minutes, Day 8: (H) 2 mg/kg administered by IV infusion over 30 minutes, Day 15: (H) 2 mg/kg administered by IV infusion over 30 minutes. Last cycle: Day 1: (T) 100mg/m2 as 1 hour IV infusion followed by (H) 2 mg/kg IV infusion over 30 minutes, Day 8: (H) 2 mg/kg administered by IV infusion over 30 minutes, Day 15: (H) 2 mg/kg administered by IV infusion over 30 minutes, Day 22: (H) 6 mg/kg administered by IV infusion over 30 minutes.

Also known as: taxotere
Herceptin plus docetaxel
trastuxumabBIOLOGICAL

Cycle 1: Day 1: Herceptin (H) 4 mg/kg loading dose administered by IV infusion over 90 minutes, Day 2: Docetaxel (T) 100 mg/m2 by IV infusion over 30 minutes, Day 8: (H) 2mg/kg administered by IV infusion over 30 minutes, Day 15: 2mg/kg administered by IV infusion over 30 minutes. Subsequent cycles: Day 1: (T) 100mg/m2 as 1 hour IV infusion given every 3 weeks, followed by (H) 2 mg/kg IV infusion over 30 minutes, Day 8: (H) 2 mg/kg administered by IV infusion over 30 minutes, Day 15: (H) 2 mg/kg administered by IV infusion over 30 minutes. Last cycle: Day 1: (T) 100mg/m2 as 1 hour IV infusion followed by (H) 2 mg/kg IV infusion over 30 minutes, Day 8: (H) 2 mg/kg administered by IV infusion over 30 minutes, Day 15: (H) 2 mg/kg administered by IV infusion over 30 minutes, Day 22: (H) 6 mg/kg administered by IV infusion over 30 minutes.

Also known as: herceptin
Herceptin plus docetaxel

Eligibility Criteria

Age18 Years - 75 Years
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed adenocarcinoma of the breast * Stage IIIB, IIIC, or IV * HER2-positive * Measurable or evaluable disease * Patients with osteolytic bone lesions as only site of disease must have at least 2 lytic sites confirmed by bone x-ray, MRI, or CT scan * None of the following are eligible as only manifestation of metastatic disease: * Blastic bone metastases * Mixed bone metastases * Lymphangitic carcinomatosis * Ascites * Pleural/pericardial effusion * Lymphangitis cutis/pulmonis * Inflammatory breast disease * Abdominal masses not confirmed and followed by imaging techniques * Cystic lesions * No prior or known concurrent clinical manifestation of brain or leptomeningeal involvement * Hormone receptor status: * Not specified PATIENT CHARACTERISTICS: Age * 18 to 75 Sex * Female Menopausal status * Pre- or post-menopausal Performance status * Karnofsky 60-100% Life expectancy * Not specified Hematopoietic * Neutrophil count at least 2,000/mm3 * Platelet count at least 100,000/mm3 * Hemoglobin at least 10 g/dL Hepatic * Bilirubin no greater than upper limit of normal (ULN) * AST and ALT no greater than 5 times ULN * Alkaline phosphatase no greater than 5 times ULN (unless due to bone metastases or any nonmalignant bone disease and in absence of liver disorders) * AST and/or ALT greater than 1.5 times ULN AND alkaline phosphatase greater than 2.5 times ULN ineligible Renal * Creatinine no greater than 2 mg/dL * Creatinine clearance at least 60 mL/min Cardiovascular * LVEF normal by MUGA or echocardiogram * No myocardial infarction within the past year * No unstable angina pectoris * No documentation of congestive heart failure * No concurrent grade 3 or 4 cardiovascular arrhythmia * No poorly controlled hypertension (i.e., diastolic pressure greater than 100 mmHg) Pulmonary * No severe dyspnea due to complications of advanced malignancy * No respiratory insufficiency requiring supplemental oxygen Other * No significant neurologic or psychiatric disorders (e.g., psychotic disorders, dementia, or seizures) that would preclude study * No pre-existing sensory or motor neuropathy grade 2 or greater * No other serious illness or medical condition * No active uncontrolled infection * No active peptic ulcer disease * No unstable diabetes mellitus * No other prior or concurrent malignancy except for: * Curatively treated nonmelanoma skin cancer * Carcinoma in situ of the cervix * Other curatively treated cancer and disease free for at least 10 years * No known allergic reactions to study drugs * No contraindications for the use of corticosteroids * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy * See Chemotherapy * No prior trastuzumab (Herceptin) for locally advanced or metastatic disease * Prior trastuzumab-containing regimen (except with taxane) as adjuvant or neoadjuvant therapy allowed provided relapse occurred at least 6 months after therapy Chemotherapy * No prior chemotherapy for locally advanced or metastatic disease or local recurrence * No prior chemotherapy with anthracycline or anthracenedione regimens with cumulative doses of more than 360 mg/m2 of doxorubicin, 720 mg/m2 of epirubicin, or 72 mg/m2 of mitoxantrone * No prior platinum-containing regimen as adjuvant or neoadjuvant chemotherapy * At least 4 weeks since prior anthracyclines or anthracenediones * Prior taxanes as adjuvant or neoadjuvant chemotherapy allowed provided relapse occurred at least 6 months after therapy * Prior taxane with trastuzumab as adjuvant or neoadjuvant chemotherapy allowed provided relapse occurred at least 12 months after therapy * No concurrent amifostine Endocrine therapy * Prior hormonal therapy in the adjuvant or metastatic setting allowed provided patient has progressive disease and therapy has stopped before study entry * Concurrent chronic corticosteroids allowed if initiated more than 6 months before study entry and at a low dose (no greater than 20 mg methylprednisolone or equivalent) * No concurrent raloxifene, tamoxifen, or other selective estrogen receptor modulators * No concurrent hormonal therapy Radiotherapy * No prior radiotherapy to study lesion unless clear progression * At least 4 weeks since prior radiotherapy (unless radiotherapy involved only a single field to treat a single metastatic bone lesion) * Concurrent radiotherapy for palliative treatment allowed Surgery * Not specified Other * Recovered from prior antitumor therapy * At least 30 days since prior experimental drugs * No other concurrent experimental drugs * No other concurrent anticancer therapy * No concurrent bisphosphonates if osteolytic bone metastases are only site of disease * If receiving concurrent bisphosphonates other than for bone metastases only, must have been started at least 3 months before study entry * No concurrent primary prophylactic antibiotics * No concurrent cardioprotectors (e.g., dexrazoxane)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

Study Sites (1)

Jonsson Comprehensive Cancer Center, UCLA

Los Angeles, California, 90095, United States

Location

Related Publications (4)

  • Press MF, Sauter G, Bernstein L, Villalobos IE, Mirlacher M, Zhou JY, Wardeh R, Li YT, Guzman R, Ma Y, Sullivan-Halley J, Santiago A, Park JM, Riva A, Slamon DJ. Diagnostic evaluation of HER-2 as a molecular target: an assessment of accuracy and reproducibility of laboratory testing in large, prospective, randomized clinical trials. Clin Cancer Res. 2005 Sep 15;11(18):6598-607. doi: 10.1158/1078-0432.CCR-05-0636.

    PMID: 16166438BACKGROUND

  • Pegram M, Forbes J, Pienkowski T, et al.: BCIRG 007: first overall survival analysis of randomized phase III trial of trastuzumab plus docetaxel with or without carboplatin as first line therapy in HER2 amplified metastatic breast cancer (MBC). [Abstract] J Clin Oncol 25 (Suppl 18): A-LBA1008, 2007.

    RESULT

  • Valero V, Roche H, Pienkowski T, et al.: BCIRG 007: serum HER2 levels in women with metastatic HER2-amplified breast cancer. [Abstract] J Clin Oncol 25 (18 Suppl 20): A-1020, 2007.

    RESULT

  • Forbes JF, Kennedy J, Pienkowski T, et al.: BCIRG 007: randomized phase III trial of trastuzumab plus docetaxel with or without carboplatin first line in HER2 positive metastatic breast cancer (MBC): main time to progression (TTP) analysis. [Abstract] J Clin Oncol 24 (Suppl 18): A-LBA516, 7s, 2006.

    RESULT

MeSH Terms

Conditions

Breast Neoplasms

Interventions

TrastuzumabCarboplatinDocetaxel

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsCoordination ComplexesOrganic ChemicalsTaxoidsCyclodecanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsDiterpenesTerpenes

Study Officials

  • Linnea Chap, MD

    C. Klien and Associates

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 3, 2002

First Posted

January 27, 2003

Study Start

May 1, 2002

Primary Completion

January 1, 2006

Study Completion

April 1, 2010

Last Updated

August 3, 2020

Record last verified: 2016-02

Locations

US(1)