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Breast NeoplasmsPhase 2NCT00263198

PTK and Letrozole in Post-menopausal Women With Advanced Breast Cancer

A Phase 2 study testing PTK787/ZK222584 and Letrozole in people with Breast Neoplasms, run by Washington University School of Medicine at 1 site in United States.

Terminated

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

Official record
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Trial summary

The purpose of this study is to test the safety of PTK787/ZK222584 and Letrozole when given in combination, and to see what effects they have on breast cancer that has metastasized. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Neoplasms
What is being tested?
PTK787/ZK222584 and Letrozole
Could I receive a placebo?
No, everyone receives an active treatment
How many people
4 participants
Where
1 siteUnited States
Study dates
Mar 2006to Nov 2006
Phase
Phase 2
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 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Postmenopausal women with metastatic breast cancer, or loco-regional disease recurrence not amenable to treatment by surgery or radiotherapy.
  • Postmenopausal status will be defined by any of the following criteria:
  • no spontaneous menses for at least 5 years
  • spontaneous menses within the past 5 years but amenorrheic for at least 12 months and estradiol and/or FSH values in the postmenopausal range (while off aromatase inhibitor therapy; levels can have been taken while on tamoxifen but in this case estradiol should be the parameter assessed)
  • bilateral oophorectomy
  • radiation castration and amenorrheic for at least 3 months
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  • the use of an LHRH agonist throughout the duration of the trial (for example goserelin 3.6 mg s.c. monthly)
  • Age ≥ 18 years old
  • Patients whose tumors are either estrogen-receptor (ER) and/or progesterone-receptor (PgR) positive (10% or more infiltrating cancer cells exhibiting nuclear staining). Patients will be regarded as ER or PgR positive as long as at least one of the tissues assessed was positive. A positive biochemical test is also acceptable.
  • Patients must have a WHO Performance Status Grade 0-2
  • Newly diagnosed patients who are initiating first line treatment or those patients with known disease who have shown resistance to anti- estrogen therapy (tamoxifen or toremifine).
  • Patients currently receiving letrozole or alternative aromatase inhibitors as initial therapy who are without evidence of progressive disease are eligible.
  • Patients with bone-only metastasis are eligible.
  • Laboratory values ≤ 2 weeks prior to randomization:
  • Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L (≥ 1500/mm3)
  • Platelets (PLT) ≥ 100 x 109/L (≥ 100,000/mm3)
  • Hemoglobin (Hgb) ≥ 9 g/dL
  • Serum creatinine ≤ 1.5 ULN
  • Serum bilirubin ≤ 1.5 ULN
  • Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤ 3.0 x ULN (≤ 5 x ULN if liver metastases present)
  • Negative for proteinuria based on dip stick reading OR, if documentation of +1 result for protein on dip stick reading, then total urinary protein
  • 500 mg and measured creatinine clearance (CrCl) ≥ 50 mL/min from a 24- hour urine collection
  • Life expectancy ≥ 12 weeks
  • Written informed consent obtained according to local guidelines

Who cannot join

  • Patients with tumors which are both estrogen and progesterone receptor negative, or estrogen receptor negative and progesterone receptor unknown or estrogen receptor unknown and progesterone receptor negative
  • Patients with a history of adrenalectomy or hypophysectomy
  • Patients who developed progressive disease while being treated with an aromatase inhibitor.
  • Patients with any of the following:
  • Absolute Neutrophil Count < 1.5 x 109/L
  • Hemoglobin < 9 g/dl
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  • Platelet count < 100 x 109/L
  • AST and ALT > 3 times the upper limit of normal or > 5 times the upper limit of normal if liver metastasis are present
  • Bilirubin > 1.5 upper limit of normal
  • Creatinine > 1.5 x upper limit of normal
  • Calcium > 11.6 mg/dL
  • History or presence of central nervous system (CNS) disease (i.e., primary brain tumor, malignant seizures, CNS metastases or carcinomatous meningitis)
  • Patients with a history of another primary malignancy ≤ 5 years that has not been treated for curative intent or that the chance of long term remission is judged to be less than 50%.
  • Prior chemotherapy <3 weeks prior to registration and/or randomization. Patients must have recovered from all therapy-related toxicities
  • Prior biologic or immunotherapy ≤ 2 weeks prior to registration and/or randomization. Patients must have recovered from all therapy-related toxicities
  • Patients with a history of treatment with Fulvestrant or Trastuzumab < 6 months prior to registration. Patients must have recovered from all therapy- related toxicities in order to be enrolled.
  • Prior full field radiotherapy ≤ 4 weeks or limited field radiotherapy ≤ 2 weeks prior to randomization. Patients must have recovered from all therapy-related toxicities. The site of previous radiotherapy should have evidence of progressive disease if this is the only site of disease
  • Major surgery (e.g., laparotomy) ≤ 4 weeks prior to randomization. Minor surgery ≤ 2 weeks prior to randomization. Insertion of a vascular access device is not considered major or minor surgery in this regard. Patients must have recovered from all surgery-related toxicities
  • Patients who have received investigational drugs ≤ 4 weeks prior to registration and/or randomization
  • Prior therapy with anti-VEGF agents
  • Peripheral neuropathy with functional impairment ≥ CTC grade 2 neuropathy, regardless of causality
  • Pleural effusion or ascites that causes respiratory compromise (≥ CTC grade 2 dyspnea)
  • Any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study:
  • Uncontrolled high blood pressure (systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 95 mmHg), history of labile hypertension, or history of poor compliance with an antihypertensive regimen
  • Unstable angina pectoris
  • Symptomatic congestive heart failure
  • Myocardial infarction ≤ 6 months prior to registration and/or randomization
  • Serious uncontrolled cardiac arrhythmia
  • Uncontrolled diabetes (fasting blood sugar > 300 mg/dl)
  • Active or uncontrolled infection
  • Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung
  • Patients with prolonged QTc > 470 msec on EKG. All patients with a history of congenital or acquired long QTc syndrome.
  • Chronic renal disease
  • Acute or chronic liver disease (e.g., hepatitis, cirrhosis)
  • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of PTK787/ZK 222584 (i.e., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, bowel obstruction, or inability to swallow the tablets)
  • Patients with confirmed diagnosis of human immunodeficiency virus (HIV) infection are excluded at the investigator's discretion if it is felt that:
  • 1) a potential drug interaction between PTK787/ZK 222584 and any of the patient's anti-HIV medications could influence the efficacy of the anti-HIV medication, or 2) it may place the patient at risk due to the pharmacologic activity of PTK787/ZK 222584. Please refer to appendix for a list of examples of substrates of human liver microsomal P450 enzymes
  • Patients who are taking therapeutic warfarin sodium (Coumadin) or similar oral anticoagulants that are metabolized by the cytochrome P450 system. Heparin in any formulation is allowed. Please refer to appendix for a list of examples of substrates of human liver microsomal P450 enzymes
  • Patients on P450 enzyme inducing anti-epileptics
  • Patients who are unwilling or unable to comply with protocol requirements.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: Phase II Study of the Combination of PTK787/ZK222584 and Letrozole in Postmenopausal Women With Advanced Hormone Receptor Positive Breast Cancer

The purpose of this study is to test the safety of PTK787/ZK222584 and Letrozole when given in combination, and to see what effects they have on breast cancer that has metastasized.

Being tested
PTK787/ZK222584, Letrozole
Medical subject headings
Breast Neoplasms

What participants receive

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

Study groups in NCT00263198
Study groupRoleWhat they receive
Letrozole + PTK787/ZK222584ExperimentalLetrozole 2.5 mg PO daily for 28 days (patients who have already been treated with letrozole for at least 28 days can skip this part) Start cycle 1 with: * Letrozole 2.5 mg PO once daily * PTK787/ZK222584 250 mg BID PO for 1 week, then 500 mg BID PO for the 2nd week followed by 500 mg qAM and 750 mg QPM PO for the subsequent 2 weeks. Subsequent cycles: * PTK787/ZK222584 500 mg qAM and 750 mg qPM PO daily * Letrozole 2.5 mg PO once daily
Receives: Drug: PTK787/ZK222584; Drug: Letrozole

What is being measured

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

  1. Assess the effect of the combination of letrozole & PTK787/ZK222584 on disease progression.

    Measured: 24 weeks after starting PTK787/ZK222584

Secondary outcomes (9)

  1. Evaluate the response rate (CR and PR)

    Measured: Completion of treatment

  2. Evaluate the safety and tolerability of the combination of drugs

    Measured: 30 days after completion of study treatment

  3. Evaluate the pharmacokinetic profiles of the combination of drugs

    Measured: Cycle 3 Day 1

  4. Evaluate the modulation of tumor blood flow and blood vessel permeability in response to PTK787/ZK222584 when administered in combination with letrozole using Dynamic Contrast-Enhanced Magnetic Resonance Imaging

    Measured: Cycle 1 Day 28

  5. Evaluate the effect on circulating tumor cells

    Determined by the commerical Immunocon cell search assay

    Measured: Completion of treatment

  6. Compare outcome of patients receiving letrozole and PTK787/ZK222584 (cases) with control patients from pivotal trials of letrozole in the first and second line setting.

    Matching the cases and controls for line of therapy, sites of disease and duration of prior aromatase inhibitor therapy before the study patient initiates PTK787/ZK222584 treatment.

    Measured: 30 days after completion of study treatment

  7. Evaluate polymorphisms in relevant drug metabolism genes to determine the molecular basis for interactions between letrozole and PTK787/ZK222584 should they occur.

    Measured: Completion of treatment

  8. Correlate serum LDH level with clinical response

    Measured: Completion of treatment

  9. With additional patient consent, collect peripheral blood cells, serum, plasma, and representative tumor tissue specimens for future correlative science studies

    Measured: Baseline visit

Timeline

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

  1. First posted7 Dec 2005 (estimated)
  2. Study startMar 2006
  3. Primary completionOct 2006
  4. Study completionNov 2006

Why it stopped: unacceptable toxicity

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
4 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00263198
Sponsor's protocol ID
05-0970
Status last verified
May 2013
First submitted
6 Dec 2005
Last updated
7 May 2013
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing PTK787/ZK222584 and Letrozole in people with Breast Neoplasms, run by Washington University School of Medicine 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?

The sponsor lists 24 inclusion and 40 exclusion criteria. 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 7 May 2013. 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 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?

The study was stopped early (reason given: unacceptable toxicity). 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?

Assess the effect of the combination of letrozole & PTK787/ZK222584 on disease progression. (time frame: 24 weeks after starting PTK787/ZK222584). 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 NCT00263198.

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 7 May 2013; AzTrials last refreshed its copy on 7 Nov 2026.

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