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

NCT00263198 | Terminated Phase 2

• 1 other identifier: 05-0970
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Breast Neoplasms

Outcome Measures

Primary Outcomes (1)

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

  24 weeks after starting PTK787/ZK222584

Secondary Outcomes (9)

• Evaluate the response rate (CR and PR)

  Completion of treatment

• Evaluate the safety and tolerability of the combination of drugs

  30 days after completion of study treatment

• Evaluate the pharmacokinetic profiles of the combination of drugs

  Cycle 3 Day 1

• 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

  Cycle 1 Day 28

• Evaluate the effect on circulating tumor cells

  Completion of treatment

Study Arms (1)

Letrozole + PTK787/ZK222584

EXPERIMENTAL

Letrozole 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

Drug: PTK787/ZK222584; Drug: Letrozole

Interventions

PTK787/ZK222584 DRUG

Letrozole + PTK787/ZK222584

Letrozole DRUG

Letrozole + PTK787/ZK222584

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Novartis: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Breast Neoplasms

Interventions

vatalanib; Letrozole

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Cynthia Ma, M.D., Ph.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2005
• First Posted: December 7, 2005
• Study Start: March 1, 2006
• Primary Completion: October 1, 2006
• Study Completion: November 1, 2006
• Last Updated: May 7, 2013

Record last verified: 2013-05

Locations

US (1)