Clinical trial NCT00004935: Herceptin Followed by Chemotherapy in Treating Women With Metastatic Breast Cancer That Overexpresses HER2
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.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Breast Cancer
Keywords: stage IV breast cancer
recurrent breast cancer
Lead sponsor: Swiss Group for Clinical Cancer Research
Sponsor class: OTHER
First posted: 2003-01-27
Enrollment: 175
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility 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

Primary outcomes:
measure: Time to progression on combined HerChemo (TTPHerChemo)
timeFrame: 8 weeks
Secondary outcomes:
measure: Response rate
timeFrame: 8 weeks
measure: Time to first progression
timeFrame: 8 weeks
measure: Time to treatment failure
timeFrame: 8 weeks
measure: Overall survival
timeFrame: 8 weeks
measure: Adverse events
timeFrame: 8 weeks
measure: Predictive value of serum HER2/neu ECD levels on clinical outcome
timeFrame: 8 weeks
measure: Conversion rate of estrogen receptor status
timeFrame: 8 weeks
measure: Association of immunoprofiles of erbB-1, erbB-2, erbB-3 and erbB-4 with clinical outcome
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Milan
country: Italy
facility: European Institute of Oncology
city: Varese
country: Italy
facility: Ospedale di Circolo e Fondazione Macchi
city: Aarau
country: Switzerland
facility: Kantonsspital Aarau
city: Baden
country: Switzerland
facility: Kantonsspital Baden
city: Basel
country: Switzerland
facility: Universitaetsspital-Basel
city: Bellinzona
country: Switzerland
facility: Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli
city: Bern
country: Switzerland
facility: Inselspital Bern
city: Chur
country: Switzerland
facility: Kantonsspital Graubuenden
city: Geneva
country: Switzerland
facility: Hopital Cantonal Universitaire de Geneve
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: Lugano
country: Switzerland
facility: Ospedale Regionale di Lugano
city: Rheinfelden
country: Switzerland
facility: Praxis Dr. Beretta
city: St. Gallen
country: Switzerland
facility: Kantonsspital - St. Gallen
city: Thun
country: Switzerland
facility: Regionalspital
city: Zurich
country: Switzerland
facility: Onkozentrum
city: Zurich
country: Switzerland
facility: City Hospital Triemli
city: Zurich
country: Switzerland
facility: UniversitaetsSpital Zuerich
Study officials:
affiliation: Istituto Oncologico della Svizzera Italiana IOSI
name: Pagani Olivia, MD
role: STUDY_CHAIR
References:
citation: Eppenberger-Castori S, Klingbiel D, Ruhstaller T, Dietrich D, Rufle DA, Rothgiesser K, Pagani O, Thurlimann B. Plasma HER2ECD a promising test for patient prognosis and prediction of response in HER2 positive breast cancer: results of a randomized study - SAKK 22/99. BMC Cancer. 2020 Feb 11;20(1):114. doi: 10.1186/s12885-020-6594-0.
citation: Schmid S, Klingbiel D, Aebi S, Goldhirsch A, Mamot C, Munzone E, Nole F, Oehlschlegel C, Pagani O, Pestalozzi B, Rochlitz C, Thurlimann B, von Moos R, Weder P, Zaman K, Ruhstaller T. Long-term responders to trastuzumab monotherapy in first-line HER-2+ advanced breast cancer: characteristics and survival data. BMC Cancer. 2019 Sep 10;19(1):902. doi: 10.1186/s12885-019-6105-3.