Herceptin Followed by Chemotherapy in Treating Women With Metastatic Breast Cancer That Overexpresses HER2

Swiss Group for Clinical Cancer Research

Status and phase: Terminated; Phase 3

Conditions: Breast Cancer

Treatments: Drug: Herceptin™ (Her) + chemo; Drug: Herceptin™ (Her)

Study type: Interventional

Funder types: Other

Identifiers

NCT00004935

SAKK 22/99

SWS-SAKK-22/99 (Other Identifier)

EU-99028 (Other Identifier)

Details and patient eligibility

About

RATIONALE: To compare efficacy, toxicity and quality of life of the sequential administration of Her alone followed, at PD, by the combination with Chemotherapy (Arm A) vs. the upfront combination of Her and Chemotherapy (Arm B) in patients with advanced/metastatic breast cancer.

PURPOSE: Trial SAKK 22/99 addresses clinically relevant and currently unresolved questions regarding the optimal use of Herceptin in the treatment of patients with advanced/metastatic breast cancer.

Full description

In advanced HER2+ breast cancer the impact of combining Trastuzumab (T) and chemotherapy (chemo) versus T alone followed by the addition of chemo at disease progression has not been properly studied.

The trial compared efficacy, toxicity and quality of life of sequential administration of T followed, at progression, by combination with chemo (T>TChemo) versus the upfront combination of T and chemo (TChemo) in patients with HER2+ advanced breast cancer.

Enrollment: 175 patients

Sex: Female

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed HER2-overexpressing metastatic breast carcinoma

• Clinically or radiologically measurable or evaluable disease

  • Bidimensionally or unidimensionally measurable lesions

• No ascitic, pleural, or pericardial effusions, osteoblastic bone metastases, or carcinomatous lymphangitis of the lung as only indicator lesion

• No known clinical brain or meningeal involvement

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Age:

• 18 to 70

Sex:

• Female

Menopausal status:

• Not specified

Performance status:

• ECOG 0-1 OR
• SAKK 0-1

Life expectancy:

• At least 12 weeks

Hematopoietic:

• Hemoglobin at least 10 g/dL
• Platelet count at least 100,000/mm^3
• Absolute neutrophil count at least 2,000/mm^3

Hepatic:

• Bilirubin normal
• SGOT and/or SGPT no greater than 2 times upper limit of normal (ULN) (3 times ULN if proven liver metastases) OR
• No SGOT and/or SGPT greater than 1.5 times ULN if alkaline phosphatase greater than 2.5 times ULN

Renal:

• Creatinine no greater than 1.25 times ULN

Cardiovascular:

• LVEF normal
• No history of atrial ventricular arrhythmia, congestive heart failure, or angina pectoris, even if medically controlled
• No history of second or third-degree heart blocks
• No uncontrolled hypertension

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No pre-existing motor or sensory neuropathy grade 2 or greater
• No psychiatric disorder that would preclude informed consent
• No other prior malignancy except curatively treated nonmelanoma skin cancer or carcinoma in situ of the cervix
• No definite contraindications for use of corticosteroids
• No other concurrent serious illness or medical condition

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• Prior adjuvant or neoadjuvant chemotherapy allowed
• No more than 2 prior chemotherapy regimens for metastatic disease
• No prior cumulative dose of doxorubicin greater than 240 mg/m^2
• No prior cumulative dose of epirubicin greater than 360 mg/m^2
• No prior taxanes

Endocrine therapy:

• Prior hormonal therapy as adjuvant treatment or for metastatic disease allowed
• No concurrent corticosteroids unless started more than 6 months prior to study and at low doses (i.e., no greater than 20 mg methylprednisolone or equivalent)

Radiotherapy:

• Not specified

Surgery:

• Not specified

Other:

• No other concurrent anticancer drugs

• No other concurrent experimental drugs

• No concurrent bisphosphonates unless initiated more than 3 months prior to study

  • Chronic use allowed provided bone metastases are not sole indicator lesions

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: None (Open label)

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175 participants in 2 patient groups

Herceptin™ (Her)

Active Comparator group

Description:

Herceptin™ (Her) loading dose 4 mg/kg iv, followed by 2 mg/kg iv weekly or loading dose 8 mg/kg iv, followed by 6 mg/kg iv every 3 weeks; at time of progression add chemotherapy

Treatment:

Drug: Herceptin™ (Her)

Herceptin™+Chemo

Active Comparator group

Description:

Herceptin™ (Her) loading dose 4 mg/kg iv, followed by 2 mg/kg iv weekly or loading dose 8 mg/kg iv, followed by 6 mg/kg iv every 3 weeks, and chemotherapy

Treatment:

Drug: Herceptin™ (Her) + chemo