Neoadjuvant Operable Breast CancerPhase 2NeoPALNCT02400567
Efficacy of Letrozole + Palbociclib Combination as Neoadjuvant Treatment of Stage II-IIIA PAM 50 ROR-defined Low or Intermediate Risk Luminal Breast Cancer, in Postmenopausal Women
A Phase 2 study testing Fluorouracile, Epirubicin and Cyclophosphamide in people with Neoadjuvant Operable Breast Cancer, run by UNICANCER at 2 sites in France.
Trial summary
The investigators propose in the present study an innovative approach, combining the most recent therapeutic opportunities in high risk ER+ breast cancer with the most recent and innovative diagnostic approaches such as the PAM50 signature and the RCB tumor response evaluation method. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Neoadjuvant Operable Breast Cancer
- What is being tested?
- Fluorouracile, Epirubicin and Cyclophosphamide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 125 participants
- Where
- 2 sitesFrance
- Study dates
- Jan 2015to Sep 2020
- 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
- Aged ≥ 18 years, Post-menopausal women
- Newly diagnosed and operable unilateral invasive breast cancer, not candidate or uncertain for breast conservation - Note: Multicentric/multifocal tumors are allowed provided a maximum of 3 lesions are present, and all share the same characteristics: ER Allred 4, Her2- (PAM50 will be performed in the largest lesion)
- Stage II-IIIA
- Assessment of nodal status available (Ultrasound guided FNA or biopsy if necessary)
- Non metastatic, M0
- ER-positive by IHC (Allred Score≥4)
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- HER2-negative by IHC (score 0 or 1+) and/or Fish/Cish
- Either Luminal A AND proven nodal involvement (cytology or histology), or Luminal B through PAM50 ROR (Prosigna™) centralized evaluation
- ECOG 0-1
- No prior systemic therapy for the present tumor
- Adequate renal, hepatic, and hematopoietic functions as defined by the following criteria:
- Absolute Neutrophil Count (ANC) ≥1,500/mm3 or ≥1.5 x 109/L
- Platelets ≥100,000/mm3 or ≥100 x 109/L
- Hemoglobin ≥9 g/dL
- Serum Aspartate Transaminase (AST) and serum Alanine Aminotransferase Transaminase (ALT) ≤2.5 x upper limit of normal (ULN)
- Alkaline phosphatase ≤2.5 x ULN
- Total serum bilirubin ≤1 x ULN
- Serum creatinine ≤1.5 x ULN or estimated creatinine clearance ≥ 60 mL/min as calculated using the method standard for the institution
- Adequate cardiac functions, including:
- 12 Lead electrocardiogram (ECG) with normal tracing or non clinically significant changes that do not require medical intervention.
- QTc interval ≤480 msec
- No history of Torsades de Pointes or other symptomatic QTc abnormality.
- Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures
- Signed informed consent and health insurance coverage
Who cannot join
- Non operable, bilateral, T4 or metastatic breast cancer
- Limited T2 breast cancer immediately accessible to conservative surgery
- Previous homolateral breast cancer (including in situ carcinoma), and/or contralateral breast cancer except if treated by surgery +/- radiation therapy alone without any systemic treatment
- Previous hormone replacement therapy (HRT) stopped less than 2 weeks before beginning of treatment
- Previous use of SERMs such as raloxifene
- Any surgery (not including minor procedures such as lymph node biopsy, primary tumor core biopsy, fine needle aspiration) within 4 weeks of start of study treatment; or not fully recovered from any side effects of previous procedures.
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- Diagnosis of any previous malignancy within the last 5 years, except for adequately treated basal cell carcinoma, or squamous cell skin carcinoma, or in situ cervical carcinoma
- History of any previous anti-cancer chemotherapy and any previous treatment using AI
- Concurrent administration of herbal preparations as complementary medicine.
- Any clinically significant gastrointestinal abnormalities, which may impair intake, transit or absorption of the study drugs, such as the inability to take oral medication in tablet form and malabsorption syndrome
- Patient with any psychological, familial, social or geographical condition which could potentially hamper compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
Trial locations and contacts
2 sites in 1 country.
About this study
Official title: Open-label, Randomized, Multicenter, International, Parallel Exploratory Phase II Study, Comparing 3 FEC-3 Docetaxel Chemotherapy to Letrozole + Palbociclib Combination as Neoadjuvant Treatment of Stage II-IIIA PAM 50 ROR-defined Low or Intermediate Risk Luminal Breast Cancer, in Postmenopausal Women
The investigators propose in the present study an innovative approach, combining the most recent therapeutic opportunities in high risk ER+ breast cancer with the most recent and innovative diagnostic approaches such as the PAM50 signature and the RCB tumor response evaluation method. In line with the most recent recommendations on targeted anticancer therapies, the investigators have designed a parallel phase II randomized trial with early stopping rules 26, which will able in the meantime to build a unique prospective collection of tumor tissue, pre- and post-treatment.
- Conditions
- Neoadjuvant Operable Breast Cancer
- Being tested
- Fluorouracile, Epirubicin, Cyclophosphamide, Letrozole, Palbociclib
- Keywords
- Luminal, Post menopausal, Breast conservation, Neoadjuvant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FluorouracileDrug
EpirubicinDrug
CyclophosphamideDrug
LetrozoleDrug
PalbociclibDrug
| Study group | Role | What they receive |
|---|---|---|
| Chemotherapy | Active comparator | 3 cycles of FEC 100 followed by 3 cycles of Docetaxel Drugs: Fluorouracile, Epirubicine, Cyclophosphamide, Docetaxel Receives: Drug: Fluorouracile; Drug: Epirubicin; Drug: Cyclophosphamide |
| Letrozole Palbociclib | Experimental | Drugs: letrozole + palbociclib combination Receives: Drug: Letrozole; Drug: Palbociclib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation of the number of patients with a Residual Cancer Burden (RCB) 0-I index as a measure of efficacy
Residual cancer burden (RCB) is estimated from routine pathologic sections of the primary breast tumor site and the regional lymph nodes after the completion of neoadjuvant therapy. 6 variables are included in a calculation formula.
Measured: 21 weeks
Secondary outcomes (4)
Evaluation of the clinical response in each treatment arm as defined by clinical and ultrasound examination.
Measured: 21 weeks
Determination of the number and type of Adverse Events as a Measure of Safety and Tolerability
The toxicity will be evaluated according to the scale CTC-AE version 4.0
Measured: 21 weeks
Correlation of the PAM50 risk of recurrence (ROR) score to its ability to predict RCB as defined in outcome 1
Measured: 21 weeks
Calculation of the rates of breast conservation therapy in the two arms with regard to the initially planned surgery.
Measured: 21 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2015 (estimated)
- Study startJan 2015
- Primary completionJan 2018
- Study completionSep 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Neoadjuvant Operable Breast CancerStudies of the same condition, open and under way.
- More trials run by UNICANCERThe 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
- 125 participants (actual)
Sponsor and investigators
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02400567
- Sponsor's protocol ID
- NeoPal - UC-0140/1404
- Other IDs
- 2014-002560-33, CARMINA04, NEOPAL, 2014
- Acronym
- NeoPAL
- Status last verified
- Mar 2022
- First submitted
- 5 Aug 2014
- Last updated
- 15 Mar 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Unicancer will share de-identified individual data that underlie the results reported. A decision concerning the sharing of other study documents, including protocol and statistical analysis plan will be examined upon request.
Publications
Cottu P, D'Hondt V, Dureau S, Lerebours F, Desmoulins I, Heudel PE, Duhoux FP, Levy C, Mouret-Reynier MA, Dalenc F, Frenel JS, Jouannaud C, Venat-Bouvet L, Nguyen S, Ferrero JM, Canon JL, Grenier J, Callens C, Gentien D, Lemonnier J, Vincent-Salomon A, Delaloge S. Letrozole and palbociclib versus chemotherapy as neoadjuvant therapy of high-risk luminal breast cancer. Ann Oncol. 2018 Dec 1;29(12):2334-2340. doi: 10.1093/annonc/mdy448.
PubMed 30307466
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-label, Randomized, Multicenter, International, Parallel Exploratory Phase II Study, Comparing 3 FEC-3 Docetaxel Chemotherapy to Letrozole + Palbociclib Combination as Neoadjuvant Treatment of Stage II-IIIA PAM 50 ROR-defined Low or Intermediate Risk Luminal Breast Cancer, in Postmenopausal Women
- ClinicalTrials.gov ID
- NCT02400567
- Acronym / sponsor ID
- NeoPAL / NeoPal - UC-0140/1404
- Conditions
- Neoadjuvant Operable Breast Cancer
- Keywords
- Luminal, Post menopausal, Breast conservation, Neoadjuvant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 125 participants (actual)
- Lead sponsor
- UNICANCERUniversity, hospital or other
- Collaborators
- Pfizer, NanoString Technologies, Inc.
- Study start
- Jan 2015 (actual)
- Primary completion
- Jan 2018 (actual)
- Study completion
- Sep 2020 (actual)
- First posted
- 27 Mar 2015 (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.
The investigators propose in the present study an innovative approach, combining the most recent therapeutic opportunities in high risk ER+ breast cancer with the most recent and innovative diagnostic approaches such as the PAM50 signature and the RCB tumor response evaluation method. In line with the most recent recommendations on targeted anticancer therapies, the investigators have designed a parallel phase II randomized trial with early stopping rules 26, which will able in the meantime to build a unique prospective collection of tumor tissue, pre- and post-treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Chemotherapy | Active comparator | Drug: Fluorouracile, Drug: Epirubicin, Drug: Cyclophosphamide3 cycles of FEC 100 followed by 3 cycles of Docetaxel Drugs: Fluorouracile, Epirubicine, Cyclophosphamide, Docetaxel |
| Letrozole Palbociclib | Experimental | Drug: Letrozole, Drug: PalbociclibDrugs: letrozole + palbociclib combination |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Aged ≥ 18 years, Post-menopausal women
- Newly diagnosed and operable unilateral invasive breast cancer, not candidate or uncertain for breast conservation - Note: Multicentric/multifocal tumors are allowed provided a maximum of 3 lesions are present, and all share the same characteristics: ER Allred 4, Her2- (PAM50 will be performed in the largest lesion)
- Stage II-IIIA
- Assessment of nodal status available (Ultrasound guided FNA or biopsy if necessary)
- Non metastatic, M0
Key exclusion criteria (11 listed)
- Non operable, bilateral, T4 or metastatic breast cancer
- Limited T2 breast cancer immediately accessible to conservative surgery
- Previous homolateral breast cancer (including in situ carcinoma), and/or contralateral breast cancer except if treated by surgery +/- radiation therapy alone without any systemic treatment
- Previous hormone replacement therapy (HRT) stopped less than 2 weeks before beginning of treatment
- Previous use of SERMs such as raloxifene
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 |
|---|---|---|
| Fluorouracile | Drug | Chemotherapy |
| Epirubicin | Drug | Chemotherapy |
| Cyclophosphamide | Drug | Chemotherapy |
| Letrozole | Drug | Letrozole Palbociclib |
| Palbociclib | Drug | Letrozole Palbociclib |
Primary outcome
Evaluation of the number of patients with a Residual Cancer Burden (RCB) 0-I index as a measure of efficacy
Time frame: 21 weeks
Residual cancer burden (RCB) is estimated from routine pathologic sections of the primary breast tumor site and the regional lymph nodes after the completion of neoadjuvant therapy. 6 variables are included in a calculation formula.
4 secondary outcomes
Evaluation of the clinical response in each treatment arm as defined by clinical and ultrasound examination.
Time frame: 21 weeks
Determination of the number and type of Adverse Events as a Measure of Safety and Tolerability
Time frame: 21 weeks
Correlation of the PAM50 risk of recurrence (ROR) score to its ability to predict RCB as defined in outcome 1
Time frame: 21 weeks
Calculation of the rates of breast conservation therapy in the two arms with regard to the initially planned surgery.
Time frame: 21 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 15 Mar 2022.
- Results publication: PubMed 30307466Cottu P, D'Hondt V, Dureau S, Lerebours F, Desmoulins I, Heudel PE, Duhoux FP, Levy C, Mouret-Reynier MA, Dalenc F, Frenel JS, Jouannaud C, Venat-Bouvet L, Nguyen S, Ferrero JM, Canon JL, Grenier J, Callens C, Gentien D, Lemonnier J, Vincent-Salomon A, Delaloge S. Letrozole and palbociclib versus chemotherapy as neoadjuvant therapy of high-risk luminal breast cancer. Ann Oncol. 2018 Dec 1;29(12):2334-2340. doi: 10.1093/annonc/mdy448.
- Ann Oncol . 2018 Dec 1;29(12):2334-2340. doi: 10.1093/annonc/mdy448Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Unicancer will share de-identified individual data that underlie the results reported. A decision concerning the sharing of other study documents, including protocol and statistical analysis plan will be examined upon request.
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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.
Paul Cottu, MD principal investigator
Institut Curie Paris
Suzette Delaloge, MD principal investigator
Gustave roussy, Villejuif
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Fluorouracile, Epirubicin and Cyclophosphamide in people with Neoadjuvant Operable Breast Cancer, run by UNICANCER at 2 sites 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 24 inclusion and 11 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 15 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
Evaluation of the number of patients with a Residual Cancer Burden (RCB) 0-I index as a measure of efficacy (time frame: 21 weeks). 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 NCT02400567, which also lists 1 linked publication.
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 15 Mar 2022.