Breast CancerPhase 1/2NCT01082068
Study of XL147 (SAR245408) or XL765 (SAR245409) in Combination With Letrozole in Subjects With Breast Cancer
A Phase 1/2 study testing XL147 (SAR245408), XL765 (SAR245409) and letrozole (Femara) in people with Breast Cancer, run by Sanofi at 17 sites in 3 countries.
Trial summary
Phase 1 of this study will evaluate the maximum tolerated dose (MTD) of XL147 when given in combination with letrozole (Femara) and of XL765 when given in combination with letrozole. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- XL147 (SAR245408), XL765 (SAR245409) and letrozole (Femara)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 17 sitesin 3 countries
- Study dates
- Jun 2010to Apr 2013
- Phase
- Phase 1/2
- 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
Who may be able to join
- The subject has histologically confirmed breast cancer that is ER+ and/or PGR+.
- The subject's breast cancer is negative for HER2.
- The subject has recurrent or metastatic breast cancer that is refractory to a nonsteroidal aromatase inhibitor and has either disease progression or disease recurrence.
- Subjects previously treated with letrozole must be able to tolerate the approved dose and schedule of letrozole.
- For subjects enrolled in Phase 2, either archival tumor samples must be available, or the subject must be willing to undergo a fresh biopsy.
- In Phase 2, at least 30 subjects in each arm must have measurable disease
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- The subject is a postmenopausal female.
- If a subject is currently receiving bisphosphonates, the subject must have received the bisphosphonates for at least 2 months before starting study treatment.
- The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1.
- The subject has adequate organ and marrow function.
- The subject has no other diagnosis of malignancy or evidence of other malignancy for 2 years before screening for this study (except non-melanoma skin cancer or in situ carcinoma of the cervix).
- The subject is capable of understanding and complying with the protocol requirements and has signed the informed consent document.
Who cannot join
- The subject has received prior treatment with a selective inhibitor of PI3K, AKT, and/or mTOR.
- Certain restrictions on prior therapies apply.
- The subject has not recovered from toxicity due to prior therapy to Grade ≤ 1 or to pre-therapy baseline.
- The subject has untreated, symptomatic, or progressive brain metastases.
- The subject has only non-measurable lesions, other than bone, skin, or chest wall metastasis
- The subject has to start cytotoxic chemotherapy due to rapid progressive disease involving major organs.
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- The subject has prothrombin time/ International Normalized Ratio (PT/ INR) or partial thromboplastin time (PTT) test results at screening that are above 1.3 x the laboratory upper limit of normal.
- The subject has uncontrolled significant intercurrent illness.
- The subject has a baseline corrected QT interval (QTc) > 470 ms.
- The subject has a diagnosis of uncontrolled diabetes mellitus.
- The subject is known to be positive for the human immunodeficiency virus (HIV).
- The subject has a previously identified allergy or hypersensitivity to components of the study treatment formulation(s).
- The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee.
Trial locations and contacts
17 sites in 3 countries.
17 sites in 3 countries
United States11 sites
Investigational Site Number 1331
Ann Arbor, Michigan, 48109
Investigational Site Number 1138
Boston, Massachusetts, 02115
Investigational Site Number 1441
Chicago, Illinois, 60611
Investigational Site Number 5201
Columbia, Missouri, 65201
Investigational Site Number 1601
Denver, Colorado, 80262
Investigational Site Number 1330
Detroit, Michigan, 48201
Investigational Site Number 1252
Durham, North Carolina, 27710
Investigational Site Number 5246
El Paso, Texas, 79915
Investigational Site Number 1238
Fort Meyers, Florida, 33901
Investigational Site Number 1537
Los Angeles, California, 90033
Investigational Site Number 1214
Nashville, Tennessee, 37203
Spain4 sites
Investigational Site Number 3415
Barcelona, 08035
Investigational Site Number 3419
Barcelona, 08036
Investigational Site Number 3413
Madrid, 28041
Investigational Site Number 3420
Madrid, 28050
France2 sites
Investigational Site Number 3321
Nantes Saint Herblain, 44805
Investigational Site Number 3324
Paris, 75231
About this study
Official title: A Phase 1/2 Dose-Escalation Study of XL147 (SAR245408) or XL765 (SAR245409) in Combination With Letrozole in Subjects With Hormone Receptor-Positive and HER2-Negative Breast Cancer Refractory to a Nonsteroidal Aromatase Inhibitor
Phase 1 of this study will evaluate the maximum tolerated dose (MTD) of XL147 when given in combination with letrozole (Femara) and of XL765 when given in combination with letrozole. After the MTD is established for each combination (Phase 2), subjects will be enrolled to evaluate the preliminary efficacy and safety of these combinations in subjects with breast cancer refractory to a non-steroidal aromatase inhibitor that is ER+/PGR+ and HER2-. Letrozole is used in the treatment of different types of breast cancer, but patients can develop resistance.
Upregulation of PI3K activity is one of the most common characteristics of human cancer cells, including breast tumor cells. Activation of PI3K results in stimulation of AKT and mTOR kinases, resulting in the promotion of tumor cell proliferation and survival. Preclinical and retrospective clinical data suggest that aberrant activation of the PI3K pathway may play a role in aromatase inhibitor resistance in patients with ER+, HER2- breast cancer. XL147 is a potent inhibitor of PI3K, and XL765 is a potent dual inhibitor of PI3K and mTOR; therefore either of these compounds in combination with letrozole warrants clinical investigation.
- Conditions
- Breast Cancer
- Being tested
- XL147 (SAR245408), XL765 (SAR245409), letrozole (Femara)
- Keywords
- HER2 negative, Hormone Receptor Positive, Breast Neoplasms
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
XL147 (SAR245408)Drug
given orally once daily as tablets
XL765 (SAR245409)Drug
given orally twice daily as capsules
letrozole (Femara)Drug
given orally once daily as tablets
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | XL147 (SAR245408) + letrozole Receives: Drug: XL147 (SAR245408); Drug: letrozole (Femara) |
| Arm 2 | Experimental | XL765 + letrozole Receives: Drug: XL765 (SAR245409); Drug: letrozole (Femara) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability of XL147 and letrozole and XL765 and letrozole
Measured: at weekly and bi-weekly study visits
In Phase 1, to determine the maximum tolerated dose of XL147 in combination with letrozole and of XL765 in combination with letrozole
Measured: assessed by weekly study visits
In Phase 2, to evaluate progression-free survival at 3 months
Measured: tumor assessments at Week 13 and every 8 weeks thereafter
Secondary outcomes (2)
In Phase 2, to assess other clinical benefit and efficacy parameters
Measured: tumor assessments at Week 13 and every 8 weeks thereafter
Pharmacokinetics and pharmacodynamics of XL147, XL765 and letrozole
Measured: assessed every 2 weeks, then every 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2010 (estimated)
- Study startJun 2010
- Primary completionApr 2013
- Study completionApr 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 SanofiThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, Study director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01082068
- Sponsor's protocol ID
- ARD11437
- Other IDs
- XL147-202
- Status last verified
- May 2016
- First submitted
- 4 Mar 2010
- Last updated
- 3 Jun 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Dose-Escalation Study of XL147 (SAR245408) or XL765 (SAR245409) in Combination With Letrozole in Subjects With Hormone Receptor-Positive and HER2-Negative Breast Cancer Refractory to a Nonsteroidal Aromatase Inhibitor
- ClinicalTrials.gov ID
- NCT01082068
- Acronym / sponsor ID
- ARD11437
- Conditions
- Breast Cancer
- Keywords
- HER2 negative, Hormone Receptor Positive, Breast Neoplasms
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Study start
- Jun 2010
- Primary completion
- Apr 2013 (actual)
- Study completion
- Apr 2013 (actual)
- First posted
- 8 Mar 2010 (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.
Phase 1 of this study will evaluate the maximum tolerated dose (MTD) of XL147 when given in combination with letrozole (Femara) and of XL765 when given in combination with letrozole. After the MTD is established for each combination (Phase 2), subjects will be enrolled to evaluate the preliminary efficacy and safety of these combinations in subjects with breast cancer refractory to a non-steroidal aromatase inhibitor that is ER+/PGR+ and HER2-. Letrozole is used in the treatment of different types of breast cancer, but patients can develop resistance.
Upregulation of PI3K activity is one of the most common characteristics of human cancer cells, including breast tumor cells. Activation of PI3K results in stimulation of AKT and mTOR kinases, resulting in the promotion of tumor cell proliferation and survival. Preclinical and retrospective clinical data suggest that aberrant activation of the PI3K pathway may play a role in aromatase inhibitor resistance in patients with ER+, HER2- breast cancer. XL147 is a potent inhibitor of PI3K, and XL765 is a potent dual inhibitor of PI3K and mTOR; therefore either of these compounds in combination with letrozole warrants clinical investigation.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: XL147 (SAR245408), Drug: letrozole (Femara)XL147 (SAR245408) + letrozole |
| Arm 2 | Experimental | Drug: XL765 (SAR245409), Drug: letrozole (Femara)XL765 + letrozole |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- The subject has histologically confirmed breast cancer that is ER+ and/or PGR+.
- The subject's breast cancer is negative for HER2.
- The subject has recurrent or metastatic breast cancer that is refractory to a nonsteroidal aromatase inhibitor and has either disease progression or disease recurrence.
- Subjects previously treated with letrozole must be able to tolerate the approved dose and schedule of letrozole.
- For subjects enrolled in Phase 2, either archival tumor samples must be available, or the subject must be willing to undergo a fresh biopsy.
Key exclusion criteria (13 listed)
- The subject has received prior treatment with a selective inhibitor of PI3K, AKT, and/or mTOR.
- Certain restrictions on prior therapies apply.
- The subject has not recovered from toxicity due to prior therapy to Grade ≤ 1 or to pre-therapy baseline.
- The subject has untreated, symptomatic, or progressive brain metastases.
- The subject has only non-measurable lesions, other than bone, skin, or chest wall metastasis
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 |
|---|---|---|
| XL147 (SAR245408)given orally once daily as tablets | Drug | Arm 1 |
| XL765 (SAR245409)given orally twice daily as capsules | Drug | Arm 2 |
| letrozole (Femara)given orally once daily as tablets | Drug | Arm 1, Arm 2 |
Primary outcome
Safety and tolerability of XL147 and letrozole and XL765 and letrozole
Time frame: at weekly and bi-weekly study visits
In Phase 1, to determine the maximum tolerated dose of XL147 in combination with letrozole and of XL765 in combination with letrozole
Time frame: assessed by weekly study visits
In Phase 2, to evaluate progression-free survival at 3 months
Time frame: tumor assessments at Week 13 and every 8 weeks thereafter
2 secondary outcomes
In Phase 2, to assess other clinical benefit and efficacy parameters
Time frame: tumor assessments at Week 13 and every 8 weeks thereafter
Pharmacokinetics and pharmacodynamics of XL147, XL765 and letrozole
Time frame: assessed every 2 weeks, then every 4 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 Jun 2016.
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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.
Clinical Sciences & Operations study director
Sanofi
17 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing XL147 (SAR245408), XL765 (SAR245409) and letrozole (Femara) in people with Breast Cancer, run by Sanofi at 17 sites in 3 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 12 inclusion and 13 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 3 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States, Spain, France. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Safety and tolerability of XL147 and letrozole and XL765 and letrozole (time frame: at weekly and bi-weekly study visits). The study lists 3 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 3 Jun 2016.