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

NCT00004935 | Terminated Phase 3 DMC

• 3 other identifiers: SAKK 22/99SWS-SAKK-22/99EU-99028
• Study Type: interventional
• Target: 175
• Locations: 2 countries
• Sites: 17

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.

Conditions

Breast Cancer

Keywords

stage IV breast cancer; recurrent breast cancer

Outcome Measures

Primary Outcomes (1)

• Time to progression on combined HerChemo (TTPHerChemo)

  8 weeks

Secondary Outcomes (8)

• Response rate

  8 weeks

• Time to first progression

  8 weeks

• Time to treatment failure

  8 weeks

• Overall survival

  8 weeks

• Adverse events

  8 weeks

Study Arms (2)

Herceptin™ (Her)

ACTIVE COMPARATOR

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

Drug: Herceptin™ (Her)

Herceptin™+Chemo

ACTIVE COMPARATOR

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

Drug: Herceptin™ (Her) + chemo

Interventions

Herceptin™ (Her) DRUG

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)

Herceptin™ (Her) + chemo DRUG

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

Herceptin™+Chemo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (17)

European Institute of Oncology

Milan, 20141, Italy

Location

Ospedale di Circolo e Fondazione Macchi

Varese, 21100, Italy

Location

Kantonsspital Aarau

Aarau, CH-5001, Switzerland

Location

Kantonsspital Baden

Baden, CH-5404, Switzerland

Location

Universitaetsspital-Basel

Basel, CH-4031, Switzerland

Location

Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli

Bellinzona, 6500, Switzerland

Location

Inselspital Bern

Bern, CH-3010, Switzerland

Location

Kantonsspital Graubuenden

Chur, 7000, Switzerland

Location

Hopital Cantonal Universitaire de Geneve

Geneva, CH-1211, Switzerland

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, CH-1011, Switzerland

Location

Ospedale Regionale di Lugano

Lugano, 6900, Switzerland

Location

Praxis Dr. Beretta

Rheinfelden, CH-4310, Switzerland

Location

Kantonsspital - St. Gallen

Sankt Gallen, CH-9007, Switzerland

Location

Regionalspital

Thun, 3600, Switzerland

Location

Onkozentrum

Zurich, 8038, Switzerland

Location

City Hospital Triemli

Zurich, 8063, Switzerland

Location

UniversitaetsSpital Zuerich

Zurich, CH-8091, Switzerland

Location

Related Publications (2)

• 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.

  PMID: 32046665 DERIVED

• 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.

  PMID: 31500588 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Trastuzumab; Drug Therapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Therapeutics

Study Officials

• Pagani Olivia, MD

  Istituto Oncologico della Svizzera Italiana IOSI

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 7, 2000
• First Posted: January 27, 2003
• Study Start: August 30, 1999
• Primary Completion: November 6, 2014
• Study Completion: March 31, 2022
• Last Updated: April 18, 2023

Record last verified: 2022-03

Locations

CH (15); IT (2)