Untreated Operable Early Breast CancerPhase 2POPNCT02008734
Randomized Phase II Study to Assess PD 0332991 in Breast Cancer
A Phase 2 study testing PD0332991 in people with Untreated Operable Early Breast Cancer, run by Gustave Roussy, Cancer Campus, Grand Paris at 1 site in France.
Trial summary
This is a Phase II study trying to identify whether short term treatment with PD0332991 yields anti-proliferative response -defined by a low level of Ki67 expression (IHC) at surgery- or induces senescence as determined by SABG expression (IHC) in tumors from patients with early breast cancer non-candidates for… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Untreated Operable Early Breast Cancer
- What is being tested?
- PD0332991
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 132 participants
- Where
- 1 siteFrance
- Study dates
- Jan 2014to Jan 2016
- Phase
- Phase 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
- Signed written informed consent
- Female patients aged 18 years or older.
- Histologically or cytologically confirmed untreated invasive carcinoma of the breast irrespective of HER2 and ER status
- No personal history of breast cancer within the last 5 years
- Candidates for initial breast surgery, with a minimum size of 15 mm measured by breast US. Bilateral and multifocal tumors are allowed, assuming tumor evaluations and pre- and post-treatment biopsies are performed in the same target lesion.
- 7. High proliferative tumor as defined by either Grade 3 or Ki67 ≥20% 8. No evidence of metastatic disease. 9. Eastern Cooperative Oncology Group (ECOG) performance status 0/1. 10. Left ventricular ejection fraction (LVEF) of at least 50% 11. Negative pregnancy test in women of childbearing potential within 14 days prior to treatment initiation (premenopausal or less than 12 months of amenorrhea post-menopause, and who have not undergone surgical sterilization).
- 12. For women of childbearing potential who are sexually active, agreement to use a highly effective, non-hormonal form of contraception or two effective forms of non-hormonal contraception during and for at least 6 months post-treatment.
- 13. Patients must be affiliated to a social security system
Who cannot join
- Patients non-candidate for upfront breast surgery or candidate for neoadjuvant chemotherapy or hormonotherapy.
- Patients with previously treated breast cancer during the last 5 years or receiving another concomitant anticancer treatment like chemotherapy, immunotherapy, endocrine
- 4. Known hypersensibility to PD0332991 or any of its components. 5. Difficulty to swallow oral medication 6. Serious uncontrolled concomitant disease that would put the patient at high risk for treatment-related complications.
- 7. Patient whose general clinical condition does not consider postponing surgery 8. Inadequate organ function, evidenced by the following laboratory results:
- Absolute neutrophil count <1,500 cells/mm3
- Platelet count <100,000 cells/mm3
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- Hemoglobin <9 g/dL
- Total bilirubin greater than 1,5 times the upper limit of normal (ULN) (unless the patient has documented Gilbert's syndrome)
- Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT]) >2.5 x ULN
- Serum creatinine >2.0 mg/dL and/or 177 μmol/L clearance creatinine <50mL/min (calculated by Cockcroft-Gault method)
- International normalized ratio (INR) and activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) >1.5 x ULN (unless on therapeutic coagulation) 9. Uncontrolled hypertension (systolic >150 mmHg and/or diastolic > 100 mmHg) or clinically significant (i.e. active) cardiovascular disease: cerebrovascular accident/stroke or myocardial infarction within 6 months prior to first study medication; unstable angina; CHF of New York Heart Association (NYHA) Grade II or higher; or serious cardiac arrhythmia requiring medication.
- 10. Patients with a history of long-QT syndrome or documented family history of long-QT syndrome.
- 11. QTc >470 12. serum potassium level < LLN 13. Uncontrolled intercurrent illness including but not limited to, known active infection with human immunodeficiency virus (HIV), hepatitis B or C virus or psychiatric illness/social situations that would limit compliance with study requirements.
- 14. Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.
- 15. Pregnant or breastfeeding patients
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomized Short-term Pre-surgical Study to Assess the Effects of PD 0332991 in Early Breast Cancer Patients
This is a Phase II study trying to identify whether short term treatment with PD0332991 yields anti-proliferative response -defined by a low level of Ki67 expression (IHC) at surgery- or induces senescence as determined by SABG expression (IHC) in tumors from patients with early breast cancer non-candidates for neoadjuvant hormonotherapy or chemotherapy, as compared to no treatment.
- Conditions
- Untreated Operable Early Breast Cancer
- Being tested
- PD0332991
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PD0332991Drug
| Study group | Role | What they receive |
|---|---|---|
| Control | No intervention | Not described |
| PD0332991 | Experimental | Patients will be randomized 3:1 to be treated with PD0332991 125mg/day orally for a total duration of 14 days (or 100 mg/day for a total duration of 21 days depending on results of interim analysis) with last treatment taken the day previous to the surgical procedure. Receives: Drug: PD0332991 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Anti proliferative response
percentage of patients who at Day 15 have a natural logarithm of percentage positive IHC staining Ki67 of <1 for each study drug (Ki67 "absolute" antiproliferative responders).
Measured: Assessed at Day 15 after randomization
Secondary outcomes (2)
Dose Limiting Toxicity
Using NCI CTCAE 4.0
Measured: Assessed at Day 8 and 15 after randomization
Ki67
Relative change from baseline to surgery in Ki67 IHC expression ("relative" antripoliferative responders)
Measured: Assessed at Day15 after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2013 (estimated)
- Study startJan 2014
- Primary completionJan 2016
- Study completionJan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Untreated Operable Early 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 132 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gustave Roussy, Cancer Campus, Grand Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Monica Arnedos, MD, Principal investigator, Gustave Roussy, Cancer Campus, Grand Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02008734
- Sponsor's protocol ID
- 2013-002967-24
- Other IDs
- 2013/2016
- Acronym
- POP
- Status last verified
- Jun 2016
- First submitted
- 2 Dec 2013
- Last updated
- 9 Jun 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Turner NC, Liu Y, Zhu Z, Loi S, Colleoni M, Loibl S, DeMichele A, Harbeck N, Andre F, Bayar MA, Michiels S, Zhang Z, Giorgetti C, Arnedos M, Huang Bartlett C, Cristofanilli M. Cyclin E1 Expression and Palbociclib Efficacy in Previously Treated Hormone Receptor-Positive Metastatic Breast Cancer. J Clin Oncol. 2019 May 10;37(14):1169-1178. doi: 10.1200/JCO.18.00925. Epub 2019 Feb 26.
PubMed 30807234Arnedos M, Bayar MA, Cheaib B, Scott V, Bouakka I, Valent A, Adam J, Leroux-Kozal V, Marty V, Rapinat A, Mazouni C, Sarfati B, Bieche I, Balleyguier C, Gentien D, Delaloge S, Lacroix-Triki M, Michiels S, Andre F. Modulation of Rb phosphorylation and antiproliferative response to palbociclib: the preoperative-palbociclib (POP) randomized clinical trial. Ann Oncol. 2018 Aug 1;29(8):1755-1762. doi: 10.1093/annonc/mdy202.
PubMed 29893769
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Short-term Pre-surgical Study to Assess the Effects of PD 0332991 in Early Breast Cancer Patients
- ClinicalTrials.gov ID
- NCT02008734
- Acronym / sponsor ID
- POP / 2013-002967-24
- Conditions
- Untreated Operable Early Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 132 participants (actual)
- Lead sponsor
- Gustave Roussy, Cancer Campus, Grand ParisUniversity, hospital or other
- Study start
- Jan 2014
- Primary completion
- Jan 2016 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 11 Dec 2013 (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 Phase II study trying to identify whether short term treatment with PD0332991 yields anti-proliferative response -defined by a low level of Ki67 expression (IHC) at surgery- or induces senescence as determined by SABG expression (IHC) in tumors from patients with early breast cancer non-candidates for neoadjuvant hormonotherapy or chemotherapy, as compared to no treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control | No intervention | – |
| PD0332991 | Experimental | Drug: PD0332991Patients will be randomized 3:1 to be treated with PD0332991 125mg/day orally for a total duration of 14 days (or 100 mg/day for a total duration of 21 days depending on results of interim analysis) with last treatment taken the day previous to the surgical procedure. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Signed written informed consent
- Female patients aged 18 years or older.
- Histologically or cytologically confirmed untreated invasive carcinoma of the breast irrespective of HER2 and ER status
- No personal history of breast cancer within the last 5 years
- Candidates for initial breast surgery, with a minimum size of 15 mm measured by breast US. Bilateral and multifocal tumors are allowed, assuming tumor evaluations and pre- and post-treatment biopsies are performed in the same target lesion.
Key exclusion criteria (15 listed)
- Patients non-candidate for upfront breast surgery or candidate for neoadjuvant chemotherapy or hormonotherapy.
- Patients with previously treated breast cancer during the last 5 years or receiving another concomitant anticancer treatment like chemotherapy, immunotherapy, endocrine
- 4. Known hypersensibility to PD0332991 or any of its components. 5. Difficulty to swallow oral medication 6. Serious uncontrolled concomitant disease that would put the patient at high risk for treatment-related complications.
- 7. Patient whose general clinical condition does not consider postponing surgery 8. Inadequate organ function, evidenced by the following laboratory results:
- Absolute neutrophil count <1,500 cells/mm3
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 |
|---|---|---|
| PD0332991 | Drug | PD0332991 |
Primary outcome
Anti proliferative response
Time frame: Assessed at Day 15 after randomization
percentage of patients who at Day 15 have a natural logarithm of percentage positive IHC staining Ki67 of <1 for each study drug (Ki67 "absolute" antiproliferative responders).
2 secondary outcomes
Dose Limiting Toxicity
Time frame: Assessed at Day 8 and 15 after randomization
Ki67
Time frame: Assessed at Day15 after randomization
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 Jun 2016.
- Derived from this study: PubMed 30807234Turner NC, Liu Y, Zhu Z, Loi S, Colleoni M, Loibl S, DeMichele A, Harbeck N, Andre F, Bayar MA, Michiels S, Zhang Z, Giorgetti C, Arnedos M, Huang Bartlett C, Cristofanilli M. Cyclin E1 Expression and Palbociclib Efficacy in Previously Treated Hormone Receptor-Positive Metastatic Breast Cancer. J Clin Oncol. 2019 May 10;37(14):1169-1178. doi: 10.1200/JCO.18.00925. Epub 2019 Feb 26.
- Derived from this study: PubMed 29893769Arnedos M, Bayar MA, Cheaib B, Scott V, Bouakka I, Valent A, Adam J, Leroux-Kozal V, Marty V, Rapinat A, Mazouni C, Sarfati B, Bieche I, Balleyguier C, Gentien D, Delaloge S, Lacroix-Triki M, Michiels S, Andre F. Modulation of Rb phosphorylation and antiproliferative response to palbociclib: the preoperative-palbociclib (POP) randomized clinical trial. Ann Oncol. 2018 Aug 1;29(8):1755-1762. doi: 10.1093/annonc/mdy202.
- Related InfoLink provided by the sponsor.
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.
Monica Arnedos, MD principal investigator
Gustave Roussy, Cancer Campus, Grand Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PD0332991 in people with Untreated Operable Early Breast Cancer, run by Gustave Roussy, Cancer Campus, Grand Paris at 1 site in France.
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 8 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 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 1 site in 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 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?
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?
Anti proliferative response (time frame: Assessed at Day 15 after randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02008734, which also lists 2 linked publications.
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 Jun 2016.