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A Phase III Study of Paclitaxel Via Weekly 1 Hour Infusion Versus Standard 3 Hour Infusion Every 3 Weeks With Herceptin (Trastuzumab) (NSC #688097) in the Treatment of Patients With/Without HER-2/Neu-Overexpressing Metastatic Breast Cancer


Phase 3
18 Years
N/A
Not Enrolling
Female
HER2-negative Breast Cancer, HER2-positive Breast Cancer, Recurrent Breast Cancer, Stage IIIC Breast Cancer, Stage IV Breast Cancer

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Trial Information

A Phase III Study of Paclitaxel Via Weekly 1 Hour Infusion Versus Standard 3 Hour Infusion Every 3 Weeks With Herceptin (Trastuzumab) (NSC #688097) in the Treatment of Patients With/Without HER-2/Neu-Overexpressing Metastatic Breast Cancer


PRIMARY OBJECTIVES:

I. To determine whether "dose dense" (DD) treatment with paclitaxel via weekly 1-hour
infusion has a significantly higher response rate than "standard" (S) paclitaxel treatment,
regardless of human epidermal growth factor receptor 2 (HER-2/neu) status and assignment to
Herceptin (trastuzumab).

II. To determine if the addition of Herceptin to DD or S paclitaxel significantly improves
the response rate as compared to DD or S paclitaxel alone for HER-2/neu non-overexpressing
metastatic breast cancer (e.g., 0 or 1+).

III. To determine whether the addition of Herceptin to chemotherapy treatment modifies the
quality of life experienced by patients with HER-2/neu non-overexpressing metastatic breast
cancer.

IV. To determine whether the quality of life experienced by patients with metastatic breast
cancer who have been treated with "standard" paclitaxel treatment differ from that of
patients treated with "dose dense" paclitaxel treatment.

V. To correlate amplification and overexpression of the growth factor receptor ErbB2 by
immunohistochemistry and fluorescent in-situ hybridization (FISH) with response rate, time
to progression, and overall survival of patients with metastatic breast cancer treated with
paclitaxel chemotherapy and paclitaxel + Herceptin.

VI. To correlate ErbB2 shed extracellular domain (ECD) with response rate, time to
progression, and overall survival of patients with metastatic breast cancer treated with
different doses and schedules of paclitaxel and paclitaxel + Herceptin. In addition, to
follow patterns of ErbB2/ECD after treatment and upon relapse.

SECONDARY OBJECTIVES:

I. To evaluate time to progression and survival of patients with HER-2 overexpressing
metastatic breast cancer treated with either DD or S paclitaxel plus weekly Herceptin.

II. To evaluate time to progression and survival of patients with HER-2 non-overexpressing
metastatic breast cancer treated with either DD or S paclitaxel alone or DD or S paclitaxel
plus weekly Herceptin.

III. To evaluate cardiac toxicity as measured by changes in LVEF from baseline to follow-up
measurements.

OUTLINE; Patients are assigned to 1 of 2 treatment groups.

GROUP I (HER2/neu non-overexpressors): Patients are randomized to 1 of 4 treatment arms.

ARM A: Patients receive paclitaxel intravenously (IV) over 3 hours every 3 weeks.

ARM B: Patients receive paclitaxel IV over 1 hour weekly.

ARM C: Patients receive paclitaxel as in Arm A. Patients also receive trastuzumab IV weekly.

ARM D: Patients receive paclitaxel as in Arm B and trastuzumab as in Arm C.

GROUP II (HER2/neu overexpression): Patients are assigned to 1 of 2 treatment arms.

ARM E: Patients receive paclitaxel and trastuzumab as in Arm C.

ARM F: Patients receive paclitaxel and trastuzumab as in Arm D.

In all arms, courses repeat every 3 weeks in the absence of disease progression or
unacceptable toxicity.

After the completion of study treatment, patients are followed up periodically for up to 5
years.


Inclusion Criteria:



- Histologically confirmed adenocarcinoma of the female breast which is inoperable,
recurrent or metastatic

- HER-2/neu status must be known at the time of protocol registration; HER-2/neu
assessment will be based on FISH analysis of either the primary tumor or a metastatic
site; a scoring of 0 or 1+ by immunohistochemistry (IHC) is considered negative; 2+
is considered negative unless confirmed by FISH positivity, in which case it should
be considered positive; 3+ by IHC is considered positive; for centers using FISH
only, a positive FISH assay by itself is sufficient to determine HER-2 positivity

- Patients with the following prior therapy are eligible:

- Patients with 0-1 prior chemotherapy regimens for metastatic or locally advanced
breast cancer, with the following exception: no prior taxane for
metastatic/locally advanced breast cancer

- Patients with 0-1 prior chemotherapy regimens in the adjuvant setting; if
adjuvant regimen included a taxane, patient must have been disease free for at
least 12 months from completion of adjuvant therapy until relapse

- Patients must be > 2 weeks from prior surgery, other than simple biopsy or
placement of venous access device; patients must be > 4 weeks from prior
chemotherapy; patients must be >6 weeks from nitrosoureas, melphalan, or
mitomycin

- Patients must be > 4 weeks from prior hormonal therapy unless tumor
measurements document clear progression while on treatment; if progression
is documented and toxicity from hormonal regimen has resolved, patients may
be placed on study > 1 week from prior hormonal therapy

- Prior Herceptin therapy is not allowed

- Patients with central nervous system metastases are eligible only if the patient has
completed cranial irradiation at least 6 months prior, is currently asymptomatic, and
is not currently receiving corticosteroids for this condition; patients with
leptomeningeal carcinoma (carcinomatous meningitis) are not eligible

- MESURABLE DISEASE: Any mass reproducibly measurable in two perpendicular dimensions,
examples include:

- Pulmonary nodules

- Hepatic lesions

- Skin nodules (if two measurements can be assigned)

- Lymph nodes

- The following lesions do not qualify as measurable:

- Central nervous system (CNS) lesions

- Bone disease only; lytic lesions should be documented and followed

- Lymphangitic pulmonary metastases (patients with lymphangitic metastases are
eligible if there are other sites of metastatic disease which can be measured)

- Lesions which have been irradiated unless there is definite documentation of
progression since radiotherapy

- A baseline assessment of left ventricular ejection fraction within 8 weeks of
registration is required (echocardiogram or resting multi gated acquisition scan
[MUGA] (radionuclide cineangiography [RNCA]) nuclear scintigraphy); patients with a
left ventricular ejection fraction (LVEF) < 45% are ineligible

- Granulocytes >= 1500/ul

- Platelet count >= 100,000/ul

- Creatinine =< 2.0 mg/dl

- Bilirubin within institutional normal limits

- Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST])

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Outcome Measure:

Response rate (complete response [CR]) and partial response [PR])

Outcome Description:

Multivariate logistic regression will be used to relate patient characteristics and pretreatment clinical variables with tumor response (complete or partial). Interim analyses will use a chi square statistic to compare response incidence by treatment arm with two-sided bounds constructed from the O'Brien-Fleming approach

Outcome Time Frame:

Up to 5 years

Safety Issue:

No

Principal Investigator

Andrew Seidman

Investigator Role:

Principal Investigator

Investigator Affiliation:

Cancer and Leukemia Group B

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-02792

NCT ID:

NCT00003440

Start Date:

July 1998

Completion Date:

Related Keywords:

  • HER2-negative Breast Cancer
  • HER2-positive Breast Cancer
  • Recurrent Breast Cancer
  • Stage IIIC Breast Cancer
  • Stage IV Breast Cancer
  • Breast Neoplasms

Name

Location

Cancer and Leukemia Group BChicago, Illinois  60606