Breast CancerPhase 1NCT00620594
A Phase I/II Study of BEZ235 in Patients With Advanced Solid Malignancies Enriched by Patients With Advanced Breast Cancer
A Phase 1 study testing BEZ235 in people with Breast Cancer and Advanced Solid Tumors, run by Novartis Pharmaceuticals at 15 sites in 5 countries.
Trial summary
This is a first-in-human, phase I/Ib clinical research study with BEZ235, an inhibitor of phosphatidylinositol 3'-kinase (PI3K). The study consists of a dose escalation part followed by a safety dose expansion part: Dose escalation part (advanced solid tumors, including patients with breast cancer being treated with… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer, Advanced Solid Tumors, Cowden Syndrome
- What is being tested?
- BEZ235
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 183 participants
- Where
- 15 sitesin 5 countries
- Study dates
- 21 Dec 2006to 8 Jan 2013
- 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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- [Single agent dose escalation arm]: Patients with histologically-confirmed, advanced unresectable solid tumors including CS patients who have progressed on (or not been able to tolerate) standard therapy within three months before screening visit or for whom no standard anticancer therapy exists.
- [Combination part]: Patients with metastatic HER2+ Breast Cancer, after failure of trastuzumab treatment. Eligible patients will have to have tumors carrying molecular alterations of PIK3CA and/or PTEN.
- [Single agent safety expansion arm]: Patients with histologically-confirmed, advanced unresectable solid tumors including CS patients who have progressed on (or not been able to tolerate) standard therapy within three months before screening visit or for whom no standard anticancer therapy exists. Patients will be prescreened for molecular alterations affecting PIK3CA and/or PTEN. Patients with NSCLC will also be pre-screened for EGFR mutation.
Who cannot join
- Patients who have brain metastases, which are progressive and/or requiring medical intervention for symptom control
- Prior treatment with a PI3K inhibitor
- Acute or chronic liver disease or renal disease
- Acute or chronic pancreatitis
- Patients with unresolved diarrhea ≥ CTCAE grade 2
- Impaired cardiac function or clinically significant cardiac diseases
Show all 15Show fewer
- Patients with diabetes mellitus requiring insulin treatment
- Patients with known coagulopathies
- Patients with a history of photosensitivity reactions to other drugs
- Any of the following ophthalmological findings:
- Progressive eye disease that could lead to severe loss of visual acuity or visual field
- loss during the study period
- Inability to perform the ophthalmic procedures required in this protocol
- Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol.
- Other protocol-defined inclusion/exclusion criteria may apply
Trial locations and contacts
15 sites in 5 countries.
15 sites in 5 countries
United States9 sites
Dana Farber Cancer Institute Clinical Trials ProjectManager
Boston, Massachusetts, 02215
Baylor Health Care System/Sammons Cancer Center Baylor- Sammons
Dallas, Texas, 75246
Cancer Centers of the Carolinas CCC Faris
Greenville, South Carolina, 29605
University of Texas/MD Anderson Cancer Center Thoractic Head/Neck Med.Onc(2)
Houston, Texas, 77030-4009
Nevada Cancer Institute NVCC - Huntsman
Las Vegas, Nevada, 89135
University of California at Los Angeles JonssonComprehensiveCancerCtr
Los Angeles, California, 90095
Sarah Cannon Research Institute Dept.ofSarahCannonCancerCtr(2)
Nashville, Tennessee, 37203
Yale University School of Medicine YaleCancerCtr-ClinTrialsOffice
New Haven, Connecticut, 06520
Tyler Cancer Center TCC
Tyler, Texas, 75702
Spain3 sites
Novartis Investigative Site
Barcelona, Catalonia, 08035
Novartis Investigative Site
Valencia, Valencia, 46009
Novartis Investigative Site
Valencia, Valencia, 46010
About this study
Official title: A Phase I/II, Multi-center, Open-label Study of BEZ235, Administered Orally on a Continuous Daily Dosing Schedule in Adult Patients With Advanced Solid Malignancies Including Patients With Advanced Breast Cancer
This is a first-in-human, phase I/Ib clinical research study with BEZ235, an inhibitor of phosphatidylinositol 3'-kinase (PI3K). The study consists of a dose escalation part followed by a safety dose expansion part:
Dose escalation part (advanced solid tumors, including patients with breast cancer being treated with trastuzumab):
Read more
Patients receive oral BEZ235 once daily on days 1-28 of the first course. Courses will repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of at least 3 patients receive escalating doses of BEZ235, as single agent or in combination with trastuzumab, until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose expected to produce during the first course of treatment dose-limiting toxicity in 33% of patients.
Once the MTD has been defined, the safety expansion parts of the trial will be opened for enrollment.
Safety dose expansion part (advanced solid tumors, including patients with breast cancer being treated with trastuzumab):
Patients will be treated with BEZ235, as single agent or in combination with trastuzumab, given at the MTD, once daily. Treatment of patients will continue until disease progression or occurrence of unacceptable side effects.
- Conditions
- Breast Cancer, Advanced Solid Tumors, Cowden Syndrome
- Being tested
- BEZ235
- Keywords
- Neoplasms, breast neoplasms, breast diseases, solid tumors, BEZ235, breast cancer, PI3K Inhibitor, Phosphatidylinositol 3, kinase, advanced
- Medical subject headings
- Breast Neoplasms, Hamartoma Syndrome, Multiple, Neoplasms, Breast Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BEZ235Drug
| Study group | Role | What they receive |
|---|---|---|
| BEZ235 Alone, Dose Escalation | Experimental | Not described Receives: Drug: BEZ235 |
| BEZ235 + trastuzumab, Dose Escalation | Experimental | Not described Receives: Drug: BEZ235 |
| BEZ235 Alone, MTD Expansion | Experimental | Not described Receives: Drug: BEZ235 |
| BEZ235 + Trastuzumab, MTD Expansion | Experimental | Not described Receives: Drug: BEZ235 |
What is being measured
The primary outcome is the main question the study is designed to answer.
determine the maximum Tolerated Dose (MTD) of BEZ235 as single agent and in combination with trastuzumab (Dose escalation part)
Measured: at end of study
assess the safety & tolerability of BEZ235 SDS as single agent and in combination with trastuzumab administered to patients at the MTD level (Safety expansion part)
Measured: at end of study
Secondary outcomes (3)
assess the safety and tolerability of the various formulations of BEZ235
Measured: at end of study
Asses the Pharmacokinetics of BEZ235 which includes AUC, Cmax, Tmax, t1/2 as endpoints
Measured: at end of study
Preliminary anti-tumor activity (tumor response) of BEZ235 SDS as single agent and in combination with trastuzumab
Measured: end of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2008 (estimated)
- Study start21 Dec 2006
- Primary completion8 Jan 2013
- Study completion8 Jan 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 183 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00620594
- Sponsor's protocol ID
- CBEZ235A2101
- Other IDs
- 2006-004353-23
- Status last verified
- Feb 2017
- First submitted
- 8 Feb 2008
- Last updated
- 9 Dec 2020
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II, Multi-center, Open-label Study of BEZ235, Administered Orally on a Continuous Daily Dosing Schedule in Adult Patients With Advanced Solid Malignancies Including Patients With Advanced Breast Cancer
- ClinicalTrials.gov ID
- NCT00620594
- Acronym / sponsor ID
- CBEZ235A2101
- Conditions
- Breast Cancer, Advanced Solid Tumors, Cowden Syndrome
- Keywords
- Neoplasms, breast neoplasms, breast diseases, solid tumors, BEZ235, breast cancer, PI3K Inhibitor, Phosphatidylinositol 3
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 183 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 21 Dec 2006 (actual)
- Primary completion
- 8 Jan 2013 (actual)
- Study completion
- 8 Jan 2013 (actual)
- First posted
- 21 Feb 2008 (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.
This is a first-in-human, phase I/Ib clinical research study with BEZ235, an inhibitor of phosphatidylinositol 3'-kinase (PI3K). The study consists of a dose escalation part followed by a safety dose expansion part:
Dose escalation part (advanced solid tumors, including patients with breast cancer being treated with trastuzumab):
Patients receive oral BEZ235 once daily on days 1-28 of the first course. Courses will repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of at least 3 patients receive escalating doses of BEZ235, as single agent or in combination with trastuzumab, until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose expected to produce during the first course of treatment dose-limiting toxicity in 33% of patients.
Once the MTD has been defined, the safety expansion parts of the trial will be opened for enrollment.
Safety dose expansion part (advanced solid tumors, including patients with breast cancer being treated with trastuzumab):
Patients will be treated with BEZ235, as single agent or in combination with trastuzumab, given at the MTD, once daily. Treatment of patients will continue until disease progression or occurrence of unacceptable side effects.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| BEZ235 Alone, Dose Escalation | Experimental | Drug: BEZ235 |
| BEZ235 + trastuzumab, Dose Escalation | Experimental | Drug: BEZ235 |
| BEZ235 Alone, MTD Expansion | Experimental | Drug: BEZ235 |
| BEZ235 + Trastuzumab, MTD Expansion | Experimental | Drug: BEZ235 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- [Single agent dose escalation arm]: Patients with histologically-confirmed, advanced unresectable solid tumors including CS patients who have progressed on (or not been able to tolerate) standard therapy within three months before screening visit or for whom no standard anticancer therapy exists.
- [Combination part]: Patients with metastatic HER2+ Breast Cancer, after failure of trastuzumab treatment. Eligible patients will have to have tumors carrying molecular alterations of PIK3CA and/or PTEN.
- [Single agent safety expansion arm]: Patients with histologically-confirmed, advanced unresectable solid tumors including CS patients who have progressed on (or not been able to tolerate) standard therapy within three months before screening visit or for whom no standard anticancer therapy exists. Patients will be prescreened for molecular alterations affecting PIK3CA and/or PTEN. Patients with NSCLC will also be pre-screened for EGFR mutation.
Key exclusion criteria (15 listed)
- Patients who have brain metastases, which are progressive and/or requiring medical intervention for symptom control
- Prior treatment with a PI3K inhibitor
- Acute or chronic liver disease or renal disease
- Acute or chronic pancreatitis
- Patients with unresolved diarrhea ≥ CTCAE grade 2
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 |
|---|---|---|
| BEZ235 | Drug | BEZ235 + Trastuzumab, MTD Expansion, BEZ235 + trastuzumab, Dose Escalation, BEZ235 Alone, Dose Escalation, BEZ235 Alone, MTD Expansion |
Primary outcome
determine the maximum Tolerated Dose (MTD) of BEZ235 as single agent and in combination with trastuzumab (Dose escalation part)
Time frame: at end of study
assess the safety & tolerability of BEZ235 SDS as single agent and in combination with trastuzumab administered to patients at the MTD level (Safety expansion part)
Time frame: at end of study
3 secondary outcomes
assess the safety and tolerability of the various formulations of BEZ235
Time frame: at end of study
Asses the Pharmacokinetics of BEZ235 which includes AUC, Cmax, Tmax, t1/2 as endpoints
Time frame: at end of study
Preliminary anti-tumor activity (tumor response) of BEZ235 SDS as single agent and in combination with trastuzumab
Time frame: end of study
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 9 Dec 2020.
- Results for CBEZ235A2101 can be found on the Novartis Clinical Trial Results WebsiteLink 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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
15 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BEZ235 in people with Breast Cancer and Advanced Solid Tumors, run by Novartis Pharmaceuticals at 15 sites in 5 countries.
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 3 inclusion and 15 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: finished, as of the sponsor's last update on 9 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States, Spain, Germany, Netherlands, United Kingdom. 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?
determine the maximum Tolerated Dose (MTD) of BEZ235 as single agent and in combination with trastuzumab (Dose escalation part) (time frame: at end of study). The study lists 2 primary outcomes in all. 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 9 Dec 2020.