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A Multicenter Phase III Randomized Trial Comparing Docetaxel (Taxotere) and Trastuzumab (Herceptin) With Docetaxel (Taxotere), Carboplatin and Trastuzumab (Herceptin) as First Line Chemotherapy for Patients With Advanced Breast Cancer Containing the HER2 Gene Amplification


Phase 3
18 Years
75 Years
Not Enrolling
Female
Breast Cancer

Thank you

Trial Information

A Multicenter Phase III Randomized Trial Comparing Docetaxel (Taxotere) and Trastuzumab (Herceptin) With Docetaxel (Taxotere), Carboplatin and Trastuzumab (Herceptin) as First Line Chemotherapy for Patients With Advanced Breast Cancer Containing the HER2 Gene Amplification


OBJECTIVES:

- Compare the time to disease progression in women with HER2-positive stage IIIB, IIIC,
or IV breast cancer treated with docetaxel and trastuzumab (Herceptin) with or without
carboplatin.

- Compare the response rate and duration of overall response in patients treated with
these regimens.

- Compare the overall survival of patients treated with these regimens.

- Compare rate of clinical benefit, defined as complete response, partial response, or
stable disease for more than 24 weeks, in patients treated with these regimens.

- Compare the toxicity of these regimens in these patients.

- Determine pathologic and molecular markers for predicting efficacy of these regimens in
these patients.

- Determine genetic and biochemical markers for predicting risk of cardiac dysfunction
and later cardiac events in patients receiving these regimens.

- Determine whether peripheral levels of shed HER2 extracellular domain constitute a
prognostic and/or predictive factor of time to progression and survival of patients
receiving these regimens.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified
according to prior adjuvant and/or neoadjuvant chemotherapy (none vs with taxanes vs without
taxanes) and participating center. Patients are randomized to 1 of 2 treatment arms.

- Arm I:

- Course 1: Patients receive trastuzumab (Herceptin) IV over 30-90 minutes on days
1, 8, and 15. Patients receive docetaxel IV over 1 hour and carboplatin IV over
30-60 minutes on day 2.

- Courses 2 and all subsequent courses: Patients receive docetaxel IV over 1 hour
and carboplatin IV over 30-60 minutes on day 1 and trastuzumab IV over 30 minutes
on days 1, 8, and 15.

- Arm II: Patients receive docetaxel and trastuzumab as in arm I. In both arms, treatment
repeats every 21 days for up to 8 courses in the absence of disease progression or
unacceptable toxicity. After completion of 8 courses, patients continue to receive
trastuzumab IV over 30 minutes every 21 days in the absence of disease progression.

Patients are followed every 2 months for 3 years.

PROJECTED ACCRUAL: A total of 250 patients (125 per treatment arm) will be accrued for this
study within 18 months.

Inclusion Criteria


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)

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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.

Outcome Time Frame:

till disease progression

Safety Issue:

No

Principal Investigator

Linnea Chap, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

C. Klien and Associates

Authority:

United States: Food and Drug Administration

Study ID:

CDR0000257580

NCT ID:

NCT00047255

Start Date:

May 2002

Completion Date:

Related Keywords:

  • Breast Cancer
  • stage IIIB breast cancer
  • stage IIIC breast cancer
  • stage IV breast cancer
  • recurrent breast cancer
  • Breast Neoplasms

Name

Location

Jonsson Comprehensive Cancer Center, UCLALos Angeles, California  90095-1781