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

April 12, 2023 updated by: Swiss Group for Clinical Cancer Research

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.

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

175

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Milan, Italy, 20141
        • European Institute of Oncology
      • Varese, Italy, 21100
        • Ospedale di Circolo e Fondazione Macchi
  • Switzerland
      • Aarau, Switzerland, CH-5001
        • Kantonsspital Aarau
      • Baden, Switzerland, CH-5404
        • Kantonsspital Baden
      • Basel, Switzerland, CH-4031
        • Universitaetsspital-Basel
      • Bellinzona, Switzerland, 6500
        • Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli
      • Bern, Switzerland, CH-3010
        • Inselspital Bern
      • Chur, Switzerland, 7000
        • Kantonsspital Graubuenden
      • Geneva, Switzerland, CH-1211
        • Hôpital Cantonal Universitaire de Genève
      • Lausanne, Switzerland, CH-1011
        • Centre Hospitalier Universitaire Vaudois
      • Lugano, Switzerland, 6900
        • Ospedale Regionale di Lugano
      • Rheinfelden, Switzerland, CH-4310
        • Praxis Dr. Beretta
      • St. Gallen, Switzerland, CH-9007
        • Kantonsspital - St. Gallen
      • Thun, Switzerland, 3600
        • Regionalspital
      • Zurich, Switzerland, 8038
        • Onkozentrum
      • Zurich, Switzerland, CH-8091
        • UniversitaetsSpital Zuerich
      • Zurich, Switzerland, 8063
        • City Hospital Triemli

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 66 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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
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
Active Comparator: Herceptin™+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
Drug: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Time to progression on combined HerChemo (TTPHerChemo)
Time Frame: 8 weeks
8 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Adverse events
Time Frame: 8 weeks
8 weeks
Response rate
Time Frame: 8 weeks
8 weeks
Time to first progression
Time Frame: 8 weeks
8 weeks
Time to treatment failure
Time Frame: 8 weeks
8 weeks
Overall survival
Time Frame: 8 weeks
8 weeks
Predictive value of serum HER2/neu ECD levels on clinical outcome
Time Frame: 8 weeks
8 weeks
Conversion rate of estrogen receptor status
Time Frame: 8 weeks
8 weeks
Association of immunoprofiles of erbB-1, erbB-2, erbB-3 and erbB-4 with clinical outcome
Time Frame: 8 weeks
8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Swiss Group for Clinical Cancer Research

Investigators

  • Study Chair: Pagani Olivia, MD, Istituto Oncologico della Svizzera Italiana IOSI

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 30, 1999

Primary Completion (Actual)

November 6, 2014

Study Completion (Actual)

March 31, 2022

Study Registration Dates

First Submitted

March 7, 2000

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Actual)

April 18, 2023

Last Update Submitted That Met QC Criteria

April 12, 2023

Last Verified

March 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SAKK 22/99
  • SWS-SAKK-22/99 (Other Identifier: SAKK)
  • EU-99028 (Other Identifier: SAKK)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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