Early Breast Cancer (Phase 2)Phase 2NCT01430585
Pre-Operative Study of PF-4691502 With Letrozole Compared To Letrozole Alone In Patients With Early Breast Cancer
A Phase 2 study testing PF-04691502, PF-04691502 in combination with Letrozole and Letrozole in people with Early Breast Cancer (Phase 2) and Advanced Breast Cancer (Phase 1b), run by Pfizer at 5 sites in 4 countries.
Trial summary
PF-04691502 is an inhibitor of PI3K and mTOR kinase. Published data support the hypothesis that a PI3K/mTOR antagonist in combination with letrozole might mitigate the intrinsic or acquired resistance to hormonal therapy and restore hormone sensitivity in high risk (high Ki-67) patient population of hormone-sensitive… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Early Breast Cancer (Phase 2), Advanced Breast Cancer (Phase 1b)
- What is being tested?
- PF-04691502, PF-04691502 in combination with Letrozole and Letrozole
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 5 sitesin 4 countries
- Study dates
- Mar 2012to Dec 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Phase 1 - Postmenopausal women with diagnosis of breast cancer, metastatic disease or locally advanced disease / Estrogen Receptor positive and HER-2 negative / candidate to receive Letrozole
- Phase 2 - Postmenopausal women with newly diagnosed primary breast cancer / Estrogen Receptor positive and HER-2 negative / Ki-67 levels >10% positive cells
- Phase 1 \& 2 - Glucose control, adequate bone marrow, liver, renal, and cardiac function
Who cannot join
- Inflammatory carcinoma / Prior therapy with an agent active on PI3K and/or mTOR / Significant gastrointestinal abnormalities, which may impair intake, transit or absorption of the study drugs / Current or anticipated need for food or drugs that are known inhibitors or inducers of CYP3A4
Trial locations and contacts
5 sites in 4 countries.
5 sites in 4 countries
Sweden2 sites
Pfizer Investigational Site
Gothenburg, 413 45
Pfizer Investigational Site
Stockholm, 171 76
About this study
Official title: An Open-Label, Randomised Phase 1b/2 Study Of PF-04691502 In Combination With Letrozole Compared With Letrozole Alone In Patients With Estrogen Receptor Positive, Her-2 Negative Early Breast Cancer
PF-04691502 is an inhibitor of PI3K and mTOR kinase. Published data support the hypothesis that a PI3K/mTOR antagonist in combination with letrozole might mitigate the intrinsic or acquired resistance to hormonal therapy and restore hormone sensitivity in high risk (high Ki-67) patient population of hormone-sensitive breast cancers. In addition, Ki-67, a marker of cellular proliferation, could be used to select those patients who benefit from treatment with a PI3K-pathway inhibitor.
Read the detailed description
The study was prematurely discontinued on 09Oct2012 due to the tolerability findings in 2 clinical studies testing PF-04691502 that have prompted the Sponsor to re-evaluate the strategic goals of the program. In the study B1271003 an unexpected frequency of severe skin toxicity was observed and in the study B1271004 5 cases of drug induced pneumonitis were reported.
- Being tested
- PF-04691502, PF-04691502 in combination with Letrozole, Letrozole
- Keywords
- Ki-67, postmenopausal early breast cancer, ER positive/HER2 negative early breast cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PF-04691502Drug
PF-04691502 administered as single agent for 2 weeks. After this period, patients in this arm will take PF-04691502 in combination with Letrozole until Week 6. Beyond Week 6, if considered appropriate, patients can be treated with the combination for up to 10 additional weeks until breast surgery.
PF-04691502 in combination with LetrozoleDrug
PF-04691502 in combination with Letrozole will be administered for 6 weeks. Beyond Week 6, if considered appropriate, patients can be treated for up to 10 additional weeks until breast surgery.
LetrozoleDrug
Letrozole will be administered for 6 weeks. Beyond Week 6, if considered appropriate, patients can be treated for up to 10 additional weeks until breast surgery.
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | Not described Receives: Drug: PF-04691502 |
| B | Experimental | Not described Receives: Drug: PF-04691502 in combination with Letrozole |
| C | Active comparator | Not described Receives: Drug: Letrozole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs): Phase 1B
An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. SAE: an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study treatment and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
Measured: Phase 1B: Baseline up to 28 days after last administration of study treatment
Change From Baseline in Ki-67 Percent Positive Tumor Cells in Biopsied Tumor Tissue at Week 6: Phase 2
Nuclear proliferation marker Ki-67 was to be assessed by immunohistochemistry technique in all specimens.
Measured: Phase 2: Baseline, Week 6
Secondary outcomes (8)
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs): Phase 2
An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. SAE: an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study treatment and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
Measured: Phase 2: Baseline up to 28 days after last administration of study treatment
Number of Participants With Clinically Significant Laboratory Tests Abnormalities: Phase 1B and 2
Laboratory analysis planned to include blood chemistry, hematology and urinalysis.
Measured: Phase 1B: Baseline up to end of treatment (Week 34); Phase 2: Baseline up to Week 16 or early termination (ET)
Number of Participants With Clinically Significant Abnormalities in Vital Signs: Phase 1B and 2
Vital signs assessments planned to include measurement of blood pressure and heart rate.
Measured: Phase 1B: Baseline up to 28 days after last dose of study treatment (Week 34); Phase 2: Baseline up to Week 16 or ET
Number of Participants With Clinically Significant Abnormalities in Corrected QT (QTc) Interval: Phase 1B
Measured: Phase 1B: Baseline up to end of treatment (Week 34)
Number of Participants With Objective Response (OR): Phase 1B and 2
Number of participants with objective response based on assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR was defined as complete disappearance of all target lesions and non-target lesions, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than [<] 10 millimeter [mm]). No appearance of new lesions and normalization of tumor marker levels. PR was defined as greater than or equal to (>=) 30 percent (%) decrease from baseline of the sum of diameters of all target lesions, using the short diameter in the sum for target nodes and the longest diameter in the sum for all other target lesions.
Measured: Phase 1B: Baseline, Week 12, end of treatment (Week 34); Phase 2: Baseline, Week 6, 16 or ET
Pharmacokinetic (PK) Parameters of PF-04691502 and Letrozole: Phase 1B and 2
Phase 1B: Following PK parameters were planned to be calculated from the plasma concentration time data using standard non-compartmental methods. For PF-04691502: area under the curve from time zero to last quantifiable concentration (AUClast), area under the curve from time zero to end of dosing interval (AUCtau), maximum observed plasma concentration (Cmax), minimum observed plasma trough concentration (Cmin), average plasma concentration (Cavg), time to reach maximum observed plasma concentration (Tmax), observed accumulation ratio (Rac [obs]); for letrozole: AUClast, Cmax. Phase 2: Following PK parameters were planned to be calculated for PF-04691502 from the plasma concentration time data using standard non-compartmental methods- AUClast, Cmax and Tmax.
Measured: Phase 1B: 0 (pre-dose), 1, 2, 4, 6, 24 hours on Day 1 (letrozole alone), Day 2 (PF-0491502 alone), Day 12, Week 5 (PF-0491502 and letrozole in combination); Phase 2: 0 (pre-dose), 1, 2, 4, 6, 24 hours on Day 1, pre-dose on Week 2, 6
Change From Baseline in Pharmacodynamic, Cell Proliferation and Survival Biomarkers in Biopsied Tumor Tissue at Week 2 and 6: Phase 2
Change from baseline in following pharmacodynamic parameters were planned to be calculated: expression and/or phosphorylation of Phosphoinositide-3-kinase (PI3K) pathway proteins in biopsied tumor tissue and markers of cell cycle and survival.
Measured: Phase 2: Baseline, Week 2, 6
Number of Participants With Genetic Alterations: Phase 2
Following genetic alterations were planned to be analyzed: mutations in Phosphoinositide 3-kinase, catalytic, alpha (PIK3CA), amplification of PIK3CA, Phosphate and tensin homolog (PTEN) deficiency, and changes in other genes or proteins in, or impacting V-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS), Insulin-like Growth Factor 1 Receptor (IGF-1R), phosphatidylinositol 3-kinase (PI3K)/ mammalian target of rapamycin (mTOR) pathway.
Measured: Phase 2: Baseline, Week 2, 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2011 (estimated)
- Study startMar 2012
- Primary completionDec 2012
- Study completionDec 2012
Why it stopped: See termination reason in detailed description.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Early Breast Cancer (Phase 2)Studies of the same condition, open and under way.
- More trials run by PfizerThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01430585
- Sponsor's protocol ID
- B1271003
- Status last verified
- Jul 2014
- First submitted
- 18 Aug 2011
- Last updated
- 12 Aug 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Randomised Phase 1b/2 Study Of PF-04691502 In Combination With Letrozole Compared With Letrozole Alone In Patients With Estrogen Receptor Positive, Her-2 Negative Early Breast Cancer
- ClinicalTrials.gov ID
- NCT01430585
- Acronym / sponsor ID
- B1271003
- Keywords
- Ki-67, postmenopausal early breast cancer, ER positive/HER2 negative early breast cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: See termination reason in detailed description.
- Enrolment
- 14 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- Mar 2012
- Primary completion
- Dec 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 8 Sep 2011 (estimated)
- Results
- Posted 12 Aug 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
PF-04691502 is an inhibitor of PI3K and mTOR kinase. Published data support the hypothesis that a PI3K/mTOR antagonist in combination with letrozole might mitigate the intrinsic or acquired resistance to hormonal therapy and restore hormone sensitivity in high risk (high Ki-67) patient population of hormone-sensitive breast cancers. In addition, Ki-67, a marker of cellular proliferation, could be used to select those patients who benefit from treatment with a PI3K-pathway inhibitor.
Detailed description
The study was prematurely discontinued on 09Oct2012 due to the tolerability findings in 2 clinical studies testing PF-04691502 that have prompted the Sponsor to re-evaluate the strategic goals of the program. In the study B1271003 an unexpected frequency of severe skin toxicity was observed and in the study B1271004 5 cases of drug induced pneumonitis were reported.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Drug: PF-04691502 |
| B | Experimental | Drug: PF-04691502 in combination with Letrozole |
| C | Active comparator | Drug: Letrozole |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Phase 1 - Postmenopausal women with diagnosis of breast cancer, metastatic disease or locally advanced disease / Estrogen Receptor positive and HER-2 negative / candidate to receive Letrozole
- Phase 2 - Postmenopausal women with newly diagnosed primary breast cancer / Estrogen Receptor positive and HER-2 negative / Ki-67 levels >10% positive cells
- Phase 1 \& 2 - Glucose control, adequate bone marrow, liver, renal, and cardiac function
Key exclusion criteria (1 listed)
- Inflammatory carcinoma / Prior therapy with an agent active on PI3K and/or mTOR / Significant gastrointestinal abnormalities, which may impair intake, transit or absorption of the study drugs / Current or anticipated need for food or drugs that are known inhibitors or inducers of CYP3A4
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 |
|---|---|---|
| PF-04691502PF-04691502 administered as single agent for 2 weeks. After this period, patients in this arm will take PF-04691502 in combination with Letrozole until Week 6. Beyond Week 6, if considered appropriate, patients can be treated with the combination for up to 10 additional weeks until breast surgery. | Drug | A |
| PF-04691502 in combination with LetrozolePF-04691502 in combination with Letrozole will be administered for 6 weeks. Beyond Week 6, if considered appropriate, patients can be treated for up to 10 additional weeks until breast surgery. | Drug | B |
| LetrozoleLetrozole will be administered for 6 weeks. Beyond Week 6, if considered appropriate, patients can be treated for up to 10 additional weeks until breast surgery. | Drug | C |
Primary outcome
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs): Phase 1B
Time frame: Phase 1B: Baseline up to 28 days after last administration of study treatment
An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. SAE: an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study treatment and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
Change From Baseline in Ki-67 Percent Positive Tumor Cells in Biopsied Tumor Tissue at Week 6: Phase 2
Time frame: Phase 2: Baseline, Week 6
Nuclear proliferation marker Ki-67 was to be assessed by immunohistochemistry technique in all specimens.
8 secondary outcomes
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs): Phase 2
Time frame: Phase 2: Baseline up to 28 days after last administration of study treatment
Number of Participants With Clinically Significant Laboratory Tests Abnormalities: Phase 1B and 2
Time frame: Phase 1B: Baseline up to end of treatment (Week 34); Phase 2: Baseline up to Week 16 or early termination (ET)
Number of Participants With Clinically Significant Abnormalities in Vital Signs: Phase 1B and 2
Time frame: Phase 1B: Baseline up to 28 days after last dose of study treatment (Week 34); Phase 2: Baseline up to Week 16 or ET
Number of Participants With Clinically Significant Abnormalities in Corrected QT (QTc) Interval: Phase 1B
Time frame: Phase 1B: Baseline up to end of treatment (Week 34)
Number of Participants With Objective Response (OR): Phase 1B and 2
Time frame: Phase 1B: Baseline, Week 12, end of treatment (Week 34); Phase 2: Baseline, Week 6, 16 or ET
Pharmacokinetic (PK) Parameters of PF-04691502 and Letrozole: Phase 1B and 2
Time frame: Phase 1B: 0 (pre-dose), 1, 2, 4, 6, 24 hours on Day 1 (letrozole alone), Day 2 (PF-0491502 alone), Day 12, Week 5 (PF-0491502 and letrozole in combination); Phase 2: 0 (pre-dose), 1, 2, 4, 6, 24 hours on Day 1, pre-dose on Week 2, 6
Change From Baseline in Pharmacodynamic, Cell Proliferation and Survival Biomarkers in Biopsied Tumor Tissue at Week 2 and 6: Phase 2
Time frame: Phase 2: Baseline, Week 2, 6
Number of Participants With Genetic Alterations: Phase 2
Time frame: Phase 2: Baseline, Week 2, 6
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
Related trials for Early Breast Cancer (Phase 2)
RecruitingPhase 2
Study of Patritumab Deruxtecan Plus Pembrolizumab With Other Anticancer Agents in Participants With High-Risk Early-Stage Triple-Negative or Hormone Receptor-Low Positive/HER-2 Negative Breast Cancer (MK-1022-010, HERTHENA-Breast-03)
Breast Neoplasms, Breast Cancer
RecruitingPhase 2
A Study of Imlunestrant (LY3484356) in Premenopausal Women With Estrogen Receptor-Positive (ER+) Human Epidermal Growth Factor Receptor 2 Negative (HER2-) Early Breast Cancer
Breast Neoplasms
RecruitingPhase 2
FLASH-Breast: Evaluating the Efficacy of Fezolinetant in Reducing Vasomotor Symptoms in Women With Breast Cancer on Endocrine Therapy
Breast Cancer Early Stage Breast Cancer (Stage 1-3)
RecruitingPhase 2
Ph2 Study for Optimization of Adjunct Systemic Therapy in HER2+ Patients, MolecularPCR Trial
Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage II Breast Cancer AJCC v8
Not yet recruitingPhase 2
Semaglutide for Weight Management During Hormone Therapy for Early Breast Cancer
Breast Cancer (Early Breast Cancer), Obesity
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.
Pfizer CT.gov Call Center study director
Pfizer
5 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PF-04691502, PF-04691502 in combination with Letrozole and Letrozole in people with Early Breast Cancer (Phase 2) and Advanced Breast Cancer (Phase 1b), run by Pfizer at 5 sites in 4 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 1 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: stopped early, as of the sponsor's last update on 12 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Sweden, Belgium, Italy, Spain. 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 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?
Yes. Results are posted in the registry (first posted 12 Aug 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs): Phase 1B (time frame: Phase 1B: Baseline up to 28 days after last administration of study treatment). 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 12 Aug 2014.