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AzTrials

Breast CancerPhase 1NCT00379509

Lapatinib and Radiation Therapy in Treating Patients With Locally Recurrent or Chemotherapy-Refractory Locally Advanced or Metastatic Breast Cancer

A Phase 1 study testing lapatinib ditosylate, TdT-mediated dUTP nick end labeling assay and gene expression analysis in people with Breast Cancer, run by UNC Lineberger Comprehensive Cancer Center at 1 site 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: Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving lapatinib together with radiation therapy may kill more tumor cells. Read more about this study

Who is it for?
Ages 18 to 120 years
Conditions the study is for
Breast Cancer
What is being tested?
lapatinib ditosylate, TdT-mediated dUTP nick end labeling assay and gene expression analysis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteUnited States
Study dates
Apr 2006to Aug 2012
Phase
Phase 1
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 120 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

DISEASE CHARACTERISTICS:

  • Diagnosis of breast cancer meeting 1 of the following criteria:
  • Locally recurrent disease
  • Locally advanced disease AND meets the following criterion:
  • Chemotherapy-refractory disease (achieved < partial response to ≥ 3 courses of neoadjuvant chemotherapy)
  • Metastatic disease
  • Evaluable disease by exam and/or imaging studies
  • Amenable to serial biopsies by skin punch, core biopsy, or fine-needle aspiration
  • Unresectable disease after standard neoadjuvant chemotherapy
  • Resectability must be determined by a surgical oncologist prior to treatment
  • Stable CNS metastases allowed
  • Hormone receptor status not specified

PATIENT CHARACTERISTICS:

  • Male or female
  • Menopausal status not specified
  • Life expectancy > 12 weeks
  • ECOG performance status 0-2
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Able to swallow and retain oral medication
  • WBC ≥ 3,000/mm³
  • ANC ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Total bilirubin normal
  • AST and ALT ≤ 2.5 times upper limit of normal
  • Creatinine normal OR creatinine clearance ≥ 60 mL/min
  • Cardiac ejection fraction normal by ECHO or MUGA
  • No other malignancy within the past 5 years
  • No concurrent disease or condition that would preclude study participation
  • No ongoing coagulopathy
  • No active severe infection

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Recovered from prior therapy
  • At least 3 weeks since prior and no other concurrent systemic therapy for breast cancer
  • At least 14 days since prior and no concurrent herbal or alternative medicine
  • At least 14 days since prior and no concurrent dietary supplement
  • At least 14 days since prior CYP3A4 inducers
  • At least 7 days since prior CYP3A4 inhibitors
  • No antacid within 1 hour before or after study drug administration
  • Concurrent bisphosphonate allowed
  • No concurrent oral glucocorticosteroid > 1.5 mg of dexamethasone (or equivalent)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

    Chapel Hill, North Carolina, 27599-7295

Other trials in United States

About this study

Official title: Phase I Radiosensitization Study of GW572016 With Biologic Correlates in Locoregionally Recurrent Breast Cancer

RATIONALE: Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving lapatinib together with radiation therapy may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of lapatinib when given together with radiation therapy in treating patients with locally recurrent or chemotherapy-refractory locally advanced or metastatic breast cancer.

Read the detailed description

OBJECTIVES:

Primary

  • Determine the toxicity of lapatinib ditosylate and radiotherapy in patients with locally recurrent breast cancer or chemotherapy-refractory, locally advanced or metastatic breast cancer.
  • Determine the impact of this drug on inhibition of receptor and downstream signal transduction pathway activation in tumor tissue, in the context of inhibitor dose escalation with or without radiotherapy.

Secondary

  • Determine, preliminarily, the efficacy of lapatinib ditosylate and radiotherapy in these patients.
  • Correlate response in these patients with inhibition of downstream signaling.
  • Assess gene expression changes in tumor biopsy samples from patients treated with lapatinib ditosylate alone or in combination with radiotherapy.

OUTLINE: This is a multicenter, parallel group, dose-escalation study of lapatinib ditosylate. Patients are stratified according to prior radiotherapy (yes vs no).

  • Group I (prior radiotherapy): Patients receive oral lapatinib ditosylate once daily in the absence of disease progression or unacceptable toxicity. Beginning on day 8 of lapatinib ditosylate therapy, patients undergo concurrent radiotherapy 5 days a week for up to 5 weeks.
  • Group II (no prior radiotherapy): Patients receive oral lapatinib ditosylate as in group I. Beginning on day 8, patients undergo concurrent radiotherapy 5 days a week for up to 7 weeks.

In each group, cohorts of 3-6 patients receive escalating doses of lapatinib ditosylate until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity during the first course.

Patients undergo skin punch or core biopsy at baseline* and on day 8 and day 15. Tumor biopsy samples are examined by IHC for evaluation of EGFR, phospho-EGFR, HER2, phospho-HER2, phospho-Akt, and phospho-MAPK. Samples are also examined for cell proliferation by Ki-67, apoptosis by TUNEL, and angiogenesis by microvessel density. Additionally, mRNA is extracted from fresh frozen samples and examined by microarray analysis.

NOTE: *Archival tissue acceptable for baseline sample, if available

Conditions
Breast Cancer
Being tested
lapatinib ditosylate, TdT-mediated dUTP nick end labeling assay, gene expression analysis, microarray analysis, immunohistochemistry staining method
Keywords
recurrent breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, stage IV breast cancer, male 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.

  • lapatinib ditosylateDrug

    Patients will be assigned in cohorts of 3. Dose levels of GW572106 will include 500mg, 1000mg,1500 mg (additional levels at 750 mg and 1250 mg will be added if needed). Lapatinib is an oral drug. It is taken every day.

  • TdT-mediated dUTP nick end labeling assayGenetic

    Genetic analysis of tumor tissue

  • gene expression analysisGenetic

    Genetic analysis of tumor tissue.

  • microarray analysisGenetic

    Genetic analysis of tumor tissue.

  • immunohistochemistry staining methodOther

    Laboratory analysis of tumor tissue.

  • biopsyProcedure or surgery

    Serial biopsies by skin punch or core biopsy or fine needle aspiration.

  • radiation therapyRadiation

    Radiotherapy will be delivered at standard dose and fractionation. For patients who have not received previous locoregional radiotherapy, 50-56 Gy will be delivered to the regional lymph nodes and/or chest wall at a dose of 2 Gy per fraction, 5 days per week followed by a boost to the sites of gross involvement to a total dose of 60-70 Gy over a course of 6-7 weeks. For patients who have received adjuvant radiotherapy, a dose of 35-45 Gy will be delivered to sites of chest wall involvement at a dose of 1.8 Gy per fraction over 4-5 weeks. In either de novo or reirradiated settings, the total dose to the brachial plexus will not exceed 60 Gy.

Study groups in NCT00379509
Study groupRoleWhat they receive
GW572016ExperimentalNot described
Receives: Drug: lapatinib ditosylate; Genetic: TdT-mediated dUTP nick end labeling assay; Genetic: gene expression analysis; Genetic: microarray analysis; Other: immunohistochemistry staining method; Procedure: biopsy; Radiation: radiation therapy

What is being measured

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

  1. Toxicity as assessed by NCI CTCAE v3.0

    Measured: 4-5 years

  2. Inhibition of receptor and downstream signal transduction pathway activation in tumor tissue as assessed by IHC

    Measured: 4-5 years

Secondary outcomes (3)

  1. Efficacy

    Measured: 4-5 years

  2. Correlation of response with inhibition of downstream signaling

    Measured: 4-5 years

  3. Gene expression

    Measured: 4-5 years

Timeline

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

  1. First posted22 Sep 2006 (estimated)
  2. Study startApr 2006
  3. Primary completionJun 2010
  4. Study completionAug 2012

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00379509
Sponsor's protocol ID
LCCC 0411
Other IDs
P30CA016086
Status last verified
Mar 2017
First submitted
20 Sep 2006
Last updated
21 Mar 2017
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing lapatinib ditosylate, TdT-mediated dUTP nick end labeling assay and gene expression analysis in people with Breast Cancer, run by UNC Lineberger Comprehensive Cancer Center at 1 site 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 21 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 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.

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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Toxicity as assessed by NCI CTCAE v3.0 (time frame: 4-5 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 NCT00379509.

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 21 Mar 2017.

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