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Breast CancerPhase 3NCT00004935

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

A Phase 3 study testing Herceptin™ (Her) and Herceptin™ (Her) + chemo in people with Breast Cancer, run by Swiss Cancer Institute at 17 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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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. Read more about this study

Who is it for?
Ages 18 to 70 years, women only
Conditions the study is for
Breast Cancer
What is being tested?
Herceptin™ (Her) and Herceptin™ (Her) + chemo
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
175 participants
Where
17 sitesin 2 countries
Study dates
30 Aug 1999to 31 Mar 2022
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • Women only
  • No healthy volunteers
  • Adult, Older adult

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 locations and contacts

17 sites in 2 countries.

17 sites in 2 countries

Switzerland15 sites

  • Kantonsspital Aarau

    Aarau, CH-5001

  • Kantonsspital Baden

    Baden, CH-5404

  • Universitaetsspital-Basel

    Basel, CH-4031

  • Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli

    Bellinzona, 6500

  • Inselspital Bern

    Bern, CH-3010

  • Kantonsspital Graubuenden

    Chur, 7000

  • Hopital Cantonal Universitaire de Geneve

    Geneva, CH-1211

  • Centre Hospitalier Universitaire Vaudois

    Lausanne, CH-1011

  • Ospedale Regionale di Lugano

    Lugano, 6900

  • Praxis Dr. Beretta

    Rheinfelden, CH-4310

  • Kantonsspital - St. Gallen

    Sankt Gallen, CH-9007

  • Regionalspital

    Thun, 3600

  • Onkozentrum

    Zurich, 8038

  • City Hospital Triemli

    Zurich, 8063

  • UniversitaetsSpital Zuerich

    Zurich, CH-8091

Other trials in Switzerland

Italy2 sites

  • European Institute of Oncology

    Milan, 20141

  • Ospedale di Circolo e Fondazione Macchi

    Varese, 21100

Other trials in Italy

About this study

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.

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.

Read the 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.

Conditions
Breast Cancer
Being tested
Herceptin™ (Her), Herceptin™ (Her) + chemo
Keywords
stage IV breast cancer, recurrent breast cancer
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 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) + chemoDrug

    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

Study groups in NCT00004935
Study groupRoleWhat they receive
Herceptin™ (Her)Active comparatorHerceptin™ (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
Receives: Drug: Herceptin™ (Her)
Herceptin™+ChemoActive comparatorHerceptin™ (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
Receives: Drug: Herceptin™ (Her) + chemo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Time to progression on combined HerChemo (TTPHerChemo)

    Measured: 8 weeks

Secondary outcomes (8)

  1. Response rate

    Measured: 8 weeks

  2. Time to first progression

    Measured: 8 weeks

  3. Time to treatment failure

    Measured: 8 weeks

  4. Overall survival

    Measured: 8 weeks

  5. Adverse events

    Measured: 8 weeks

  6. Predictive value of serum HER2/neu ECD levels on clinical outcome

    Measured: 8 weeks

  7. Conversion rate of estrogen receptor status

    Measured: 8 weeks

  8. Association of immunoprofiles of erbB-1, erbB-2, erbB-3 and erbB-4 with clinical outcome

    Measured: 8 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jan 2003 (estimated)
  2. Study start30 Aug 1999
  3. Primary completion6 Nov 2014
  4. Study completion31 Mar 2022

Why it stopped: Trial is Life long follow-up: to reduce ressources and costs - trial terminated prematurely.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Factorial
Masking
None (open label)
Enrolment
175 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00004935
Sponsor's protocol ID
SAKK 22/99
Other IDs
SWS-SAKK-22/99, EU-99028
Status last verified
Mar 2022
First submitted
7 Mar 2000
Last updated
18 Apr 2023
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 32046665

  • 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.

    PubMed 31500588

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Herceptin™ (Her) and Herceptin™ (Her) + chemo in people with Breast Cancer, run by Swiss Cancer Institute at 17 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 18 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in Switzerland, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Trial is Life long follow-up: to reduce ressources and costs - trial terminated prematurely.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time to progression on combined HerChemo (TTPHerChemo) (time frame: 8 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00004935, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Apr 2023.

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