- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00508586
PTC299 and Hormonal Agent for Treatment of Metastatic Breast Cancer
March 1, 2016 updated by: PTC Therapeutics
A Phase 1b Study to Assess the Safety, Feasibility, Pharmacokinetics, and Activity of PTC299 Monotherapy or Combination Therapy With Hormonal Agents in Patients With Metastatic Breast Cancer
Formation of new blood vessels (angiogenesis) is important for tumor growth in metastatic breast cancer.
It is known that tumors make a protein called vascular endothelial growth factor (VEGF) and there are higher levels of VEGF in the tumors and blood of many women with metastatic breast cancer.
VEGF stimulates the formation of blood vessels that supply the tumor with nutrients and oxygen.
PTC299 is an oral drug that has been shown to decrease production of VEGF in animal models of human cancer.
In these animal models, oral PTC299 administration decreases VEGF levels in the tumor and in the bloodstream, decreases blood vessel numbers in the tumor, and significantly slows or halts tumor growth.
Safety studies in research animals indicate good tolerability at doses and drug levels that are higher than those planned for the clinical studies.
Results from Phase 1a studies in healthy volunteers indicate that PTC299 achieves levels of PTC299 in the bloodstream that are known to be active in animal models of human cancer.
This Phase 1b study is designed to test the hypothesis that PTC299 will be tolerable and will show evidence of VEGF reduction and antitumor activity when administered orally in combination with anastrozole (Arimidex®), letrozole (Femara®), or exemestane (Aromasin®) to women with metastatic breast cancer.
Study Overview
Detailed Description
The study will be conducted in 2 stages.
In Stage 1 of the study, successive groups of 3 to 6 patients will receive progressively higher PTC299 dose levels; in this stage, treatment will be given in repeated 6-week cycles consisting of 4 weeks of oral PTC299 twice per day followed by a 2-week, no-drug period.
During Stage 2, study candidates must be women with natural or induced suppression of ovarian function to post-menopausal levels who are receiving or are candidates for hormonal therapy.
These subjects will receive continuous administration of PTC299, 100 mg/dose BID, in repeated 6-week cycles in combination with continuous administration of one of 3 hormonal agents.
All planned PTC299 dose levels in all stages are expected to achieve circulating blood levels of PTC299 known to be active in animal models of human cancer.
Treatment for each patient can continue as long as the therapy appears to be safely offering tumor control to that patient.
Up to 36 evaluable patients will be accrued across both stages.
Study Type
Interventional
Enrollment (Actual)
33
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Indiana
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Indianapolis, Indiana, United States, 46202
- Indiana University Simon Cancer Center
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New York
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New York, New York, United States, 10065
- Memorial Sloan-Kettering Cancer Center
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New York, New York, United States, 10016
- New York University Clinical Cancer Center
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
Female
Description
Major Eligibility Criteria:
- Female sex.
- Age ≥18 years.
- Body weight 40-100 kg.
- ECOG performance status of 0 or 1.
- Histologically or cytologically confirmed adenocarcinoma of the breast.
- Presence of metastatic disease not amenable to surgery, radiation therapy, or chemoradiotherapy with curative intent.
- No active second metastatic malignancy other than breast cancer.
- No unstable brain or leptomeningeal disease.
- Discontinuation of other therapies (except for anastrozole, letrozole, or exemestane) for the treatment of breast cancer and resolution of any acute toxic effects of prior therapies.
- Adequate bone marrow, liver, and kidney function.
- No uncontrolled hypertension, major bleeding, HIV infection or recent acute cardiovascular event.
- If sexually active and not postmenopausal or surgically sterile, willingness to abstain from sexual intercourse or employ an effective barrier method of contraception during the study drug administration and follow-up periods.
- No pregnancy or breast-feeding.
- Willingness and ability to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions.
- Willingness to provide informed consent. In addition to the criteria noted above, Stage 2 subjects must also have natural or induced suppression of ovarian function to post-menopausal levels and be receiving or be a candidate for hormonal therapy.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 1
PTC299 with an aromatase inhibitor
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PTC299 orally administered twice per day given in combination with anastrozole (Arimidex®), letrazole (Femara®), or exemestane (Aromasin®)
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Maximum Tolerated Dose (MTD) within the tested dose range.
Time Frame: 6 Weeks
|
6 Weeks
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Overall safety profile
Time Frame: 6 Weeks
|
6 Weeks
|
Study drug compliance
Time Frame: 6 Weeks
|
6 Weeks
|
Pharmacokinetics
Time Frame: 6 Weeks
|
6 Weeks
|
Circulating angiogenic markers
Time Frame: 6 Weeks
|
6 Weeks
|
Tumor perfusion as assessed by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)
Time Frame: 6 Weeks
|
6 Weeks
|
Tumor metabolism as assessed by fluorodeoxyglucose positron emission tomography (FDG-PET)
Time Frame: 6 Weeks
|
6 Weeks
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Antitumor activity as assessed by computed tomography (CT) scans and tumor markers
Time Frame: 6 Weeks
|
6 Weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Study Director: Jay Barth, MD, PTC Therapeutics, Inc.
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
November 1, 2007
Primary Completion (Actual)
March 1, 2012
Study Completion (Actual)
March 1, 2012
Study Registration Dates
First Submitted
July 26, 2007
First Submitted That Met QC Criteria
July 26, 2007
First Posted (Estimate)
July 30, 2007
Study Record Updates
Last Update Posted (Estimate)
March 3, 2016
Last Update Submitted That Met QC Criteria
March 1, 2016
Last Verified
April 1, 2012
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- PTC299-ONC-003-BRC
- BC050203
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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