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Breast CancerPhase 1/2NCT00086957

Gefitinib, Trastuzumab, and Docetaxel in Treating Patients With Metastatic Breast Cancer

A Phase 1/2 study testing trastuzumab, docetaxel and gefitinib in people with Breast Cancer, run by City of Hope Medical Center at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

RATIONALE: Gefitinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Cancer
What is being tested?
trastuzumab, docetaxel and gefitinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
31 participants
Where
6 sitesUnited States
Study dates
Jan 2004to Aug 2015
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

DISEASE CHARACTERISTICS:

  • Histologically confirmed adenocarcinoma of the breast
  • Metastatic disease
  • HER-2/neu overexpression (3+ by immunohistochemistry OR 2+ by fluorescence in situ hybridization)
  • Measurable or evaluable disease
  • Hormone receptor status:
  • Not specified

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Sex

  • Male or female

Menopausal status

  • Not specified

Performance status

  • ECOG 0-2

Life expectancy

  • Not specified

Hematopoietic

  • Absolute granulocyte count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3

Hepatic

  • AST and ALT < 2.5 times upper limit of normal (ULN) (5.0 times ULN in the presence of liver metastases)
  • Bilirubin < 1.5 times ULN
  • No unstable or uncompensated hepatic disease

Renal

  • Creatinine < 1.6 mg/dL
  • No unstable or uncompensated renal disease

Cardiovascular

  • LVEF > 45% by echocardiogram or MUGA
  • No prior New York Heart Association class I-IV heart disease
  • No prolonged PR interval or atrioventricular block on ECG
  • No unstable or uncompensated cardiac disease

Pulmonary

  • No unstable or uncompensated respiratory disease
  • No clinically active interstitial lung disease
  • Patients who are asymptomatic and have chronic stable radiographic changes are allowed

Immunologic

  • No autoimmune disorders
  • No conditions of immunosuppression
  • No severe hypersensitivity to taxane or gefitinib or any of its excipients

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No other prior or concurrent malignancy within the past 5 years except basal cell carcinoma or carcinoma in situ of the cervix
  • No other severe or uncontrolled systemic disease
  • No other acute or chronic medical condition that would preclude study participation
  • No other significant clinical disorder or laboratory finding that would preclude study participation
  • No psychiatric illness that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Prior adjuvant trastuzumab (Herceptin®) allowed if > 6 months elapsed before disease recurrence
  • No prior trastuzumab for metastatic breast cancer
  • No prior monoclonal antibodies directed at the epidermal growth factor receptor (EGFR)

Chemotherapy

  • Prior adjuvant chemotherapy (or as first-line therapy for metastatic breast cancer) allowed
  • Prior adjuvant taxane allowed if completed > 6 months before diagnosis of metastatic breast cancer
  • No prior docetaxel for metastatic breast cancer

Endocrine therapy

  • Prior adjuvant hormonal therapy (or as first-line therapy for metastatic breast cancer) allowed
  • No concurrent hormonal therapy
  • Concurrent steroids allowed provided dose is stable

Radiotherapy

  • Not specified

Surgery

  • Fully recovered from prior oncologic or other major surgery
  • No concurrent surgery within 7 days of gefitinib administration

Other

  • Recovered from prior anticancer therapy (alopecia allowed)
  • More than 30 days since prior non-approved drug or investigational agent
  • No other prior EGFR-directed therapy (i.e., tyrosine kinase inhibitors)
  • No concurrent use of any of the following medications:
  • Phenytoin
  • Carbamazepine
  • Barbiturates
  • Rifampin
  • Hypericum perforatum (St. John's wort)
  • No other concurrent anticancer therapy
  • No concurrent cardioprotective drugs
  • No concurrent oral retinoids
  • Concurrent participation in the City of Hope indium-labeled trastuzumab imaging study allowed

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Tower Cancer Research Foundation

    Beverly Hills, California, 90211-1850

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010-3000

  • Hematology Oncology Consultants-Hemet

    Hemet, California, 92543

  • Breastlink Medical Group, Incorporated at Long Beach Memorial Medical Center

    Long Beach, California, 90806

  • USC/Norris Comprehensive Cancer Center and Hospital

    Los Angeles, California, 90089-9181

  • City of Hope Medical Group

    Pasadena, California, 91105

Other trials in United States

About this study

Official title: Phase I/II Trial of ZD1839 (Iressa®), Trastuzumab (Herceptin®), and Docetaxel (Taxotere®) in Patients With erbB-2 (HER-2) Overexpressing, Stage IV Breast Carcinoma

RATIONALE: Gefitinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining gefitinib and trastuzumab with docetaxel may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the best dose of docetaxel when given together with gefitinib and trastuzumab in treating patients with metastatic breast cancer.

Read the detailed description

OBJECTIVES:

Primary

  • Determine the safety and efficacy of gefitinib, trastuzumab (Herceptin®), and docetaxel, in terms of time to disease progression, in patients with HER2/neu-overexpressing metastatic adenocarcinoma of the breast.

Secondary

  • Determine the objective tumor response rate in patients treated with this regimen.
  • Correlate expression and/or degree of phosphorylation of epidermal growth factor receptor, HER2/neu, c-fos, Akt, ERK½, P13K, p53, p21, and p27 with outcome in patients treated with this regimen.

OUTLINE: This is a phase I, multicenter, dose-escalation study of docetaxel followed by a phase II study. Patients are stratified according to trastuzumab (Herceptin®)-naive vs trastuzumab-failure.

  • Phase I: Patients receive oral gefitinib once daily on days 2-14. Patients also receive trastuzumab* IV over 30-90 minutes and docetaxel IV over 1 hour on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

NOTE: *Trastuzumab is given at a higher dose (loading dose) in course 1 and then at a lower dose in subsequent courses.

Cohorts of 3-6 patients receive docetaxel at dose level 1. If no dose-limiting toxicity (DLT) is observed in the first cohort of 3 patients, the dose of docetaxel remains the same. If 1 DLT is observed in the first cohort of 3 patients, 3 additional patients are added (for a total of 6 patients) to dose level 1. If no further DLTs are observed at dose level 1, the dose of docetaxel remains the same. If 2 of 3 or 2 of 6 patients experience DLT at dose level 1, the dose of docetaxel is considered above the maximum tolerated dose (MTD) and is subsequently reduced. If 2 of 3 or 2 of 6 patients experience DLT at the reduced dose of docetaxel, the study is stopped.

  • Phase II: Patients receive docetaxel at the MTD and gefitinib and trastuzumab as in phase I.

Patients are followed for survival.

PROJECTED ACCRUAL: A total of 3-76 patients will be accrued for this study within 26 months.

Conditions
Breast Cancer
Keywords
stage IV breast cancer, male breast cancer, recurrent breast cancer
Medical subject headings
Breast Neoplasms, Breast Neoplasms, Male

What participants receive

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

  • trastuzumabBiological

    Cycle 1 loading dose of 8 mg/kg, followed by 6 mg/kg every 3 weeks for subsequent cycles.

  • docetaxelDrug

    75 mg/m2 every three weeks, or 60 mg/m2 every three weeks depending on study findings

  • gefitinibDrug

    250 mg daily or 250 mg daily on days 2 through 14 depending on study findings

Study groups in NCT00086957
Study groupRoleWhat they receive
ZD1839, Trastuzumab and DocetaxelExperimentalNot described
Receives: Biological: trastuzumab; Drug: docetaxel; Drug: gefitinib

What is being measured

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

  1. Number of Participants With at Least One Dose Limiting Toxicity in Phase I

    Dose Limiting Toxicity (DLT) defined as any treatment-related grade 3 or greater except for hematological toxicities which must be grade 4. Interstitial Lung Disease (ILD) related to treatment should be considered as a DLT regardless of the grade.

    Measured: 4 weeks from start of treatment, up to 2 years

  2. Recommended Phase II Dose

    The maximum tolerated dose (MTD): subjects received gefitinib 250 mg orally daily, trastuzumab 6 mg/kg intravenously every 3 weeks (after an initial dose of 8 mg/kg with cycle 1), and docetaxel 75 mg/m^2 intravenously every 3 weeks. This was to serve as the phase II dose if no dose-limiting toxicities (DLTs) occurred in the first three subjects. If one DLT occurred in the first three subjects, another three subjects where to be enrolled at this dose, whereas if two DLTs occurred in the first three subjects, the docetaxel dose was to be decreased to 60 mg/m^2. The study would then be continued only if no more than one patient had a DLT at this dose. Once the dose of docetaxel was established, all further subjects were to be treated at the phase II MTD dose.

    Measured: 4 weeks from start of treatment, up to 2 years

Secondary outcomes (3)

  1. Progression-free Survival

    Estimated using the product-limit method of Kaplan and Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as a 20% increase in the sum of the longest diameter of target lesions, or the appearance of new lesions.

    Measured: Until disease progression, up to 5 years.

  2. Objective Response Rate

    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective Response Rate defined as percentage of patients achieving a Best Response of either CR or PR.

    Measured: After 3 cycles of treatment, up to 2 years.

  3. Overall Survival

    Estimated using the product-limit method of Kaplan and Meier.

    Measured: Until death from any cause, up to 5 years.

Timeline

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

  1. First posted12 Jul 2004 (estimated)
  2. Study startJan 2004
  3. Primary completionAug 2015
  4. Study completionAug 2015

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
31 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00086957
Sponsor's protocol ID
03049
Other IDs
P30CA033572, CHNMC-03049, ZENECA-1839US/0274, ZENECA-IRUSIRES0012, CDR0000371908
Status last verified
Jan 2017
First submitted
8 Jul 2004
Last updated
27 Feb 2017
Data monitoring committee
Yes

Publications

  • Somlo G, Koczywas M, Luu T, et al.: A phase I-II study of trastuzumab, gefitinib, and docetaxel as first line chemotherapy in patients with HER-2 overexpressing stage IV breast carcinoma. [Abstract] Breast Cancer Research and Treatment 94 (Suppl 1): A-2035, 2005.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing trastuzumab, docetaxel and gefitinib in people with Breast Cancer, run by City of Hope Medical Center at 6 sites in United States.

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: finished, as of the sponsor's last update on 27 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Feb 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Participants With at Least One Dose Limiting Toxicity in Phase I (time frame: 4 weeks from start of treatment, up to 2 years). The study lists 2 primary outcomes in all. 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 NCT00086957, which also lists 1 linked publication.

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 27 Feb 2017.

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