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

Breast Cancer Clinical Trial

Official title:

Randomized Phase III Trial of Herceptin® Followed by Chemotherapy Plus Herceptin® Versus the Combination of Herceptin® and Chemotherapy as Palliative Treatment in Patients With HER2- Overexpressing Advanced/Metastatic Breast Cancer.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00004935
• Other study ID #: SAKK 22/99
• Secondary ID: SWS-SAKK-22/99EU
• Status: Terminated
• Phase: Phase 3
• Start date: August 30, 1999
• Est. completion date: March 31, 2022

Study information

• Verified date: March 2022
• Source: Swiss Group for Clinical Cancer Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 175
• Est. completion date: March 31, 2022
• Est. primary completion date: November 6, 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Herceptin™ (Her)
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
• Herceptin™ (Her) + chemo
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

Locations

Country	Name	City	State
Italy	European Institute of Oncology	Milan
Italy	Ospedale di Circolo e Fondazione Macchi	Varese
Switzerland	Kantonsspital Aarau	Aarau
Switzerland	Kantonsspital Baden	Baden
Switzerland	Universitaetsspital-Basel	Basel
Switzerland	Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli	Bellinzona
Switzerland	Inselspital Bern	Bern
Switzerland	Kantonsspital Graubuenden	Chur
Switzerland	Hopital Cantonal Universitaire de Geneve	Geneva
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne
Switzerland	Ospedale Regionale di Lugano	Lugano
Switzerland	Praxis Dr. Beretta	Rheinfelden
Switzerland	Kantonsspital - St. Gallen	St. Gallen
Switzerland	Regionalspital	Thun
Switzerland	City Hospital Triemli	Zurich
Switzerland	Onkozentrum	Zurich
Switzerland	UniversitaetsSpital Zuerich	Zurich

Sponsors (1)

Lead Sponsor	Collaborator
Swiss Group for Clinical Cancer Research

Countries where clinical trial is conducted

Italy,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to progression on combined HerChemo (TTPHerChemo)		8 weeks
Secondary	Response rate		8 weeks
Secondary	Time to first progression		8 weeks
Secondary	Time to treatment failure		8 weeks
Secondary	Overall survival		8 weeks
Secondary	Adverse events		8 weeks
Secondary	Predictive value of serum HER2/neu ECD levels on clinical outcome		8 weeks
Secondary	Conversion rate of estrogen receptor status		8 weeks
Secondary	Association of immunoprofiles of erbB-1, erbB-2, erbB-3 and erbB-4 with clinical outcome		8 weeks