Palbociclib Plus Letrozole in Hormone Receptor Positive Residual Disease After Neoadjuvant Chemotherapy
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|ClinicalTrials.gov Identifier: NCT04130152|
Recruitment Status : Recruiting
First Posted : October 17, 2019
Last Update Posted : July 29, 2020
|Condition or disease||Intervention/treatment||Phase|
|Breast Cancer||Drug: Palbociclib Drug: Letrozole||Early Phase 1|
This is a single-arm window of opportunity trial to evaluate biologic and anti-proliferative effects of palbociclib and letrozole in HR+/HER2-negative operable BC patients with residual disease after NAC and help to identify biomarkers for better patient selection.
The primary endpoint will be the Complete Cell Cycle Arrest (CCCA) determined by Ki67<2.7%, centrally assessed at surgery after 4 weeks of palbociclib and letrozole.
Tumor measurement will be performed by ultrasound (US) for disease evaluation and confirmation of residual disease will be performed at screening at the end of NAC. The biopsy after chemotherapy will only be done after confirmation of residual disease by US. Ki67% ≥ 5% after NAC by local determination will be necessary to be included in the study.
Patients will be administered palbociclib at a dose of 125 mg once daily, day 1 to day 21 followed by 7 days off treatment in a 28-day cycle and letrozole: oral, 2.5 mg per day continuously, one cycle of treatment.
After the finalization of the neoadjuvant treatment, patients will undergo surgery. Surgery specimens will be collected for histological examination and biomarker analysis
The end of the study is defined as the date of post-surgery visit and will take place 4 weeks (+/- 7days) after the surgery in order to monitor the patient's safety and collect the surgery information.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Palbociclib in Combination With Letrozole in Patients With Hormone Receptor (HR) Positive/Human Epidermal Growth Factor Receptor 2 (HER2) Negative Residual Disease After Standard Neoadjuvant Chemotherapy (PROMETEO II)|
|Actual Study Start Date :||November 21, 2019|
|Estimated Primary Completion Date :||December 2020|
|Estimated Study Completion Date :||March 2022|
Experimental: Palbociclib + Letrozole
Palbociclib 125 mg once daily, day 1 to day 21, followed by 7 days off treatment in a 28-day cycle Letrozole: oral, 2.5 mg per day continuously. during the 28-day cycle.
If the patient is pre-menopausal, ovarian suppression with luteinizing hormone-releasing hormone (LHRH) analogues (ie, triptorelin 3.75 mg intra-muscular (IM) or Goserelin 3,6 mg SC) must be initiated at least 2 weeks before palbociclib plus letrozole administration.
Palbociclib 125 mg once daily, day 1 to day 21, followed by 7 days off treatment in a 28-day cycle
Other Name: Ibrance
Letrozole: oral, 2.5 mg per day continuously. during the 28-day cycle.
- Complete Cell Cycle Arrest (CCCA) [ Time Frame: Ki67 will be determined at surgery by central laboratory ]Complete Cell Cycle Arrest (CCCA) determined by Ki67< 2.7% at surgery following treatment with palbociclib plus letrozole, by central laboratory
- Residual Cancer Burden (RCB) [ Time Frame: Pretreated sample before NAC, after NAC and at surgery 4 weeks after palbociclib and letrozole treatment ]Changes in Ki67 between baseline samples (before NAC), residual disease samples after NAC and surgical samples following palbociclib with letrozole.
- Residual Cancer Burden (RCB) [ Time Frame: At surgery, 4 weeks after palbociclib and letrozole treatment ]Rate of RCB score 0 or 1 (RCB 0/1) after neoadjuvant treatment, according to the MD Anderson Cancer Center procedures, as per local assessment
- Pathological complete response (pCR) [ Time Frame: At surgery, 4 weeks after palbociclib and letrozole treatment ]Rate of pCR (ypT0/TisypN0) defined as the complete absence of invasive carcinoma in the breast and axillary lymph nodes on histological examination at the time of definitive surgery, irrespective of in situ carcinoma in the breast and in the breast and axilla by local evaluation.
- Incidence, duration and severity of Adverse Events (AEs) [ Time Frame: Up to 4 weeks ]Incidence and severity of treatment-emergent and treatment-related adverse events assessed by the NCI Common Terminology for Classification of Adverse Events (CTCAE) version 5.0, including dose reductions, delays and treatment discontinuations.
- Change in gene expression of 752 genes [ Time Frame: Gene expression will be analyzed in pretreated sample and at surgery 4 weeks after palbociclib and letrozole treatment ]Gene expression changes of 752 genes in all the patients, between posttreatment and pretreatment samples following therapy with palbociclib and letrozole.
- Changes of the PAM50 intrinsic subtypes [ Time Frame: Intrinsic subtype will be evaluated in pretreated sample, after NAC, and at surgery following therapy with palbociclib and letrozole. ]To evaluate the changes of the PAM50 intrinsic subtypes between samples
- Rate of cell cycle suppression according to breast cancer subtype. [ Time Frame: At surgery, 4 weeks after palbociclib and letrozole treatment ]To determine the association between PAM50 intrinsic subtypes and biological response following neoadjuvant treatment
- Correlation of rate of cell cycle suppression with gene expression changes of 752 genes. [ Time Frame: Cell cycle suppression and gene expression will be evaluated pretreatment and at surgery 4 weeks after palbociclib and letrozole treatment. ]To determine the association between gene expression from pre-treatment samples with biological response after neoadjuvant treatment.
- Correlation of pCR and RCB with gene expression changes of 752 genes. [ Time Frame: At surgery, 4 weeks after palbociclib and letrozole treatment ]To determine the association between gene expression from pre-treatment samples with pathological response after letrozole and palbociclib treatment.
- Changes in tumor-infiltrating lymphocytes (TILs) [ Time Frame: At surgery, 4 weeks after palbociclib and letrozole treatment ]Changes in TILs by immunohistochemistry (eg, percentages (%) of stromal TILs) in lesions before and after treatment.
- Changes in Programmed death-ligand 1 (PDL1) expression [ Time Frame: At surgery, 4 weeks after palbociclib and letrozole treatment ]Changes in PDL1 expression immuno-histochemistry (IHC) in lesions before and after treatment.
- Increase in CelTIL score [ Time Frame: At surgery, 4 weeks after palbociclib and letrozole treatment ]
CelTIL score is a metric for quantifying broad changes to the tumor microenvironment and is calculated by the following equation:
CelTIL score = -0.8 × tumor cellularity (in percent) + 1.3 × TILs (in percent). The minimum and maximum unscaled CelTIL scores will be -80 and 130. This unscaled CelTIL score will then be scaled to reflect the reported values ranging from 0 to 100 points where an increase in CelTIL scores represent favorable changes to the tumor microenvironment.
- Changes in ctDNA [ Time Frame: ctDNA evaluation will be performed post-NAC and at surgery, 4 weeks after palbociclib and letrozole treatment. ]Determination of changes in ctDNA in plasma samples
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04130152
|Contact: Pamela Celiz, MD, PhDemail@example.com|
|Contact: Amparo Buenestado, PhDfirstname.lastname@example.org|
|Hospital General de Catalunya||Recruiting|
|Hospital 12 de octubre||Recruiting|
|Hospital Universitario Infanta Sofía||Recruiting|
|Hospital Virgen de la Victoria||Recruiting|
|Hospital Son Espases||Recruiting|
|Palma De Mallorca, Spain|
|Complejo Hospitalario Santiago de Compostela (CHUS)||Recruiting|
|Santiago De Compostela, Spain|
|Hospital Virgen del Rocío||Recruiting|