Metastatic Breast CancerPhase 1NCT00508586
PTC299 and Hormonal Agent for Treatment of Metastatic Breast Cancer
A Phase 1 study testing PTC299 in people with Metastatic Breast Cancer, run by PTC Therapeutics at 3 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Metastatic Breast Cancer
- What is being tested?
- PTC299
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 3 sitesUnited States
- Study dates
- Nov 2007to Mar 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 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
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.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Indiana University Simon Cancer Center
Indianapolis, Indiana, 46202
New York University Clinical Cancer Center
New York, New York, 10016
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
About this study
Official title: 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.
Read the 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.
- Conditions
- Metastatic Breast Cancer
- Being tested
- PTC299
- Keywords
- Breast cancer, PTC299, VEGF, Angiogenesis, Post-transcriptional control, Aromatase inhibitors
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PTC299Drug
PTC299 orally administered twice per day given in combination with anastrozole (Arimidex®), letrazole (Femara®), or exemestane (Aromasin®)
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | PTC299 with an aromatase inhibitor Receives: Drug: PTC299 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) within the tested dose range.
Measured: 6 Weeks
Secondary outcomes (7)
Overall safety profile
Measured: 6 Weeks
Study drug compliance
Measured: 6 Weeks
Pharmacokinetics
Measured: 6 Weeks
Circulating angiogenic markers
Measured: 6 Weeks
Tumor perfusion as assessed by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)
Measured: 6 Weeks
Tumor metabolism as assessed by fluorodeoxyglucose positron emission tomography (FDG-PET)
Measured: 6 Weeks
Antitumor activity as assessed by computed tomography (CT) scans and tumor markers
Measured: 6 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2007 (estimated)
- Study startNov 2007
- Primary completionMar 2012
- Study completionMar 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- PTC Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- United States Department of Defense
- Responsible party
- Sponsor
- Investigators
- Jay Barth, MD, Study director, PTC Therapeutics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00508586
- Sponsor's protocol ID
- PTC299-ONC-003-BRC
- Other IDs
- BC050203
- Status last verified
- Apr 2012
- First submitted
- 26 Jul 2007
- Last updated
- 3 Mar 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT00508586
- Acronym / sponsor ID
- PTC299-ONC-003-BRC
- Conditions
- Metastatic Breast Cancer
- Keywords
- Breast cancer, PTC299, VEGF, Angiogenesis, Post-transcriptional control, Aromatase inhibitors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- PTC TherapeuticsIndustry (pharma, biotech, devices)
- Collaborators
- United States Department of Defense
- Study start
- Nov 2007
- Primary completion
- Mar 2012 (actual)
- Study completion
- Mar 2012 (actual)
- First posted
- 30 Jul 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: PTC299PTC299 with an aromatase inhibitor |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PTC299PTC299 orally administered twice per day given in combination with anastrozole (Arimidex®), letrazole (Femara®), or exemestane (Aromasin®) | Drug | 1 |
Primary outcome
Maximum Tolerated Dose (MTD) within the tested dose range.
Time frame: 6 Weeks
7 secondary outcomes
Overall safety profile
Time frame: 6 Weeks
Study drug compliance
Time frame: 6 Weeks
Pharmacokinetics
Time frame: 6 Weeks
Circulating angiogenic markers
Time frame: 6 Weeks
Tumor perfusion as assessed by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)
Time frame: 6 Weeks
Tumor metabolism as assessed by fluorodeoxyglucose positron emission tomography (FDG-PET)
Time frame: 6 Weeks
Antitumor activity as assessed by computed tomography (CT) scans and tumor markers
Time frame: 6 Weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2016.
- PTC Therapeutics, Inc. web siteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jay Barth, MD study director
PTC Therapeutics, Inc.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PTC299 in people with Metastatic Breast Cancer, run by PTC Therapeutics at 3 sites 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 3 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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?
Maximum Tolerated Dose (MTD) within the tested dose range. (time frame: 6 Weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 3 Mar 2016.