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


Phase 2
18 Years
N/A
Not Enrolling
Female
Breast Neoplasms

Thank you

Trial Information

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


Inclusion Criteria:



- 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

- 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

Exclusion Criteria:

- 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

- 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.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Time Frame:

24 weeks after starting PTK787/ZK222584

Safety Issue:

No

Principal Investigator

Cynthia Ma, M.D., Ph.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Washington University School of Medicine

Authority:

United States: Food and Drug Administration

Study ID:

05-0970

NCT ID:

NCT00263198

Start Date:

March 2006

Completion Date:

November 2006

Related Keywords:

  • Breast Neoplasms
  • Breast Neoplasms
  • Neoplasms

Name

Location

Washington University School of MedicineSaint Louis, Missouri  63110