Study Of Letrozole With Or Without Palbociclib (PD-0332991) For The First-Line Treatment Of Hormone-Receptor Positive Advanced Breast Cancer

• ClinicalTrials.gov Identifier: NCT00721409
• Recruitment Status: Completed
• First Posted: July 24, 2008
• Results First Posted: March 19, 2015
• Last Update Posted: November 4, 2019
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Study Description

Brief Summary:

The study is aimed to confirm that letrozole + PD 0332991 is safe and tolerable and to assess the effect of the combination on advanced breast cancer

Condition or disease	Intervention/treatment	Phase
Breast Cancer	Drug: PD 0332991; Drug: letrozole	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 177 participants
• Allocation: Randomized
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: PHASE 1/2, OPEN-LABEL, RANDOMIZED STUDY OF THE SAFETY, EFFICACY, AND PHARMACOKINETICS OF LETROZOLE PLUS PD 0332991 (ORAL CDK 4/6 INHIBITOR) AND LETROZOLE SINGLE AGENT FOR THE FIRST-LINE TREATMENT OF ER POSITIVE, HER2 NEGATIVE ADVANCED BREAST CANCER IN POSTMENOPAUSAL WOMEN
• Actual Study Start Date: September 15, 2008
• Actual Primary Completion Date: November 29, 2013
• Actual Study Completion Date: December 20, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: Arm A; letrozole + PD 0332991	Drug: PD 0332991; 125 mg/d capsules orally for 3 out of 4 weeks in repeated cycles; Drug: letrozole; 2.5 mg/d tablets orally on a continuous regimen
Active Comparator: Arm B; letrozole	Drug: letrozole; 2.5 mg/d tablets orally on a continuous regimen

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Treatment-Emergent Adverse Events (TEAEs; All Causalities) at Phase 1 [ Time Frame: Maximum treatment duration (approximately 55 months) ]
   An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was 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.
2. Number of Participants With Treatment-Related Adverse Events at Phase 1 [ Time Frame: Maximum treatment duration (approximately 55 months) ]
   An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was 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.
3. Number of Participants With Dose Limiting Toxicities at Phase 1 [ Time Frame: Cycle 2 (4 weeks) ]
   Dose limiting toxicity was defined as any of the following TEAEs occurring during the second cycle of treatment and possibly attributable to the combination of letrozole plus Palbociclib: 1. Grade 4 hematologic toxicity (including platelets <25,000/μL, ANC <500/μL). 2. Grade 3 neutropenia associated with a documented infection or fever ≥38.5°C. 3. Grade ≥3 non-hematologic toxicities, except those that have not been maximally treated (eg, nausea, vomiting, diarrhea, hypertension). 4. Delay by ≥1 week in receiving the next scheduled dose of either study treatment due to persisting treatment-related toxicities (platelet count <50,000/μL; ANC <1,000/μL; nonhematologic toxicities of Grade ≥3 severity). 5. Inability to deliver at least 80% of the planned Palbociclib or letrozole doses during Cycle 2 due to toxicity possibly attributable to the study treatment.
4. Progression-Free Survival (PFS) at Phase 2 - Investigator Assessment [ Time Frame: From randomization date to date of first documentation of progression or death (assessed up to 41 months) ]
   PFS was defined as the time from randomization (or the first dose of study treatment for non-randomized studies) to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first. PFS calculated as (Weeks or Months) = (first event date minus randomization or the first dose date plus 1) divided by 7 (or 30.44 if in months). PFS is usually characterized by the median, 25% percentile,75% percentile and their 95% Confidence Intervals (CIs).

Secondary Outcome Measures :

1. Objective Response Rate - Percentage of Participants With Confirmed Objective Tumor Response at Phase 1 [ Time Frame: From Baseline up to end of study (assessed up to 55 months) ]
   Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. Per RECIST v1.0: CR defined as disappearance of all target lesions and non-target lesions. PR defined as ≥30% decrease in sum of the longest diameters (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST associated to non-progressive disease response for non target lesions.
2. Percentage of Participants With Clinical Benefit Response (CBR) at Phase 1 [ Time Frame: From Baseline up to end of study (assessed up to 55 months) ]
   CBR is defined as a confirmed CR, confirmed PR, or stable disease (SD) for at least 24 weeks on study according to RECIST. Confirmed responses are those that persisted on repeat imaging >= 4 weeks after initial response.
3. Summary of Plasma Palbociclib Steady-state Pharmacokinetic Parameter Following Palbociclib Alone and in Combination With Letrozole: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC24) at Phase 1 [ Time Frame: Cycle 1 Day 14, and Cycle 2 Day 14 ]
   On Cycle 1 Day 14, plasma pharmacokinetic samples were collected prior to and 1, 2, 4, 8, 12, 24, 48, 96 and 120 hours after Palbociclib dosing. On Cycle 2 Day 14, plasma pharmacokinetic samples for Palbociclib and letrozole were collected prior to and 1, 2, 4, 8, 12 and 24 hours after Palbociclib and letrozole dosing.
4. Summary of Plasma Palbociclib Steady-state Pharmacokinetic Parameter Following Palbociclib Alone and in Combination With Letrozole: Maximum Observed Plasma Concentration (Cmax) at Phase 1 [ Time Frame: Cycle 1 Day 14, and Cycle 2 Day 14 ]
   On Cycle 1 Day 14, plasma pharmacokinetic samples were collected prior to and 1, 2, 4, 8, 12, 24, 48, 96 and 120 hours after Palbociclib dosing. On Cycle 2 Day 14, plasma pharmacokinetic samples for Palbociclib and letrozole were collected prior to and 1, 2, 4, 8, 12 and 24 hours after Palbociclib and letrozole dosing.
5. Summary of Plasma Palbociclib Steady-state Pharmacokinetic Parameter Following Palbociclib Alone and in Combination With Letrozole: Time to Maximum Plasma Concentration (Tmax) at Phase 1 [ Time Frame: Cycle 1 Day 14, and Cycle 2 Day 14 ]
   On Cycle 1 Day 14, plasma pharmacokinetic samples were collected prior to and 1, 2, 4, 8, 12, 24, 48, 96 and 120 hours after Palbociclib dosing. On Cycle 2 Day 14, plasma pharmacokinetic samples for Palbociclib and letrozole were collected prior to and 1, 2, 4, 8, 12 and 24 hours after Palbociclib and letrozole dosing.
6. Summary of Plasma Palbociclib Steady-state Pharmacokinetic Parameter Following Palbociclib Alone and in Combination With Letrozole: Terminal Plasma Half-life (t1/2) at Phase 1 [ Time Frame: Cycle 1 Day 14, and Cycle 2 Day 14 ]
   On Cycle 1 Day 14, plasma pharmacokinetic samples were collected prior to and 1, 2, 4, 8, 12, 24, 48, 96 and 120 hours after Palbociclib dosing. On Cycle 2 Day 14, plasma pharmacokinetic samples for Palbociclib and letrozole were collected prior to and 1, 2, 4, 8, 12 and 24 hours after Palbociclib and letrozole dosing.
7. Summary of Plasma Palbociclib Steady-state Pharmacokinetic Parameter Following Palbociclib Alone and in Combination With Letrozole: Apparent Clearance (CL/F) at Phase 1 [ Time Frame: Cycle 1 Day 14, and Cycle 2 Day 14 ]
   On Cycle 1 Day 14, plasma pharmacokinetic samples were collected prior to and 1, 2, 4, 8, 12, 24, 48, 96 and 120 hours after Palbociclib dosing. On Cycle 2 Day 14, plasma pharmacokinetic samples for Palbociclib and letrozole were collected prior to and 1, 2, 4, 8, 12 and 24 hours after Palbociclib and letrozole dosing.
8. Summary of Plasma Palbociclib Steady-state Pharmacokinetic Parameter Following Palbociclib Alone and in Combination With Letrozole: Apparent Volume of Distribution (Vz/F) at Phase 1 [ Time Frame: Cycle 1 Day 14, and Cycle 2 Day 14 ]
   On Cycle 1 Day 14, plasma pharmacokinetic samples were collected prior to and 1, 2, 4, 8, 12, 24, 48, 96 and 120 hours after Palbociclib dosing. On Cycle 2 Day 14, plasma pharmacokinetic samples for Palbociclib and letrozole were collected prior to and 1, 2, 4, 8, 12 and 24 hours after Palbociclib and letrozole dosing.
9. Summary of Plasma Letrozole Pharmacokinetic Parameter Following Letrozole Alone and in Combination With Palbociclib: AUC24 at Phase 1 [ Time Frame: Cycle 2 Day 14, Cycle 2 Day 28 ]
   On Cycle 2 Day 14, plasma pharmacokinetic samples for Palbociclib and letrozole were collected prior to and 1, 2, 4, 8, 12 and 24 hours after Palbociclib and letrozole dosing. On Cycle 2 Day 28, plasma pharmacokinetic samples were collected prior to and 1, 2, 4, 8, 12, and 24 hours after letrozole dosing.
10. Summary of Plasma Letrozole Pharmacokinetic Parameter Following Letrozole Alone and in Combination With Palbociclib: Cmax at Phase 1 [ Time Frame: Cycle 2 Day 14, and Cycle 2 Day 28 ]
    On Cycle 2 Day 14, plasma pharmacokinetic samples for Palbociclib and letrozole were collected prior to and 1, 2, 4, 8, 12 and 24 hours after Palbociclib and letrozole dosing. On Cycle 2 Day 28, plasma pharmacokinetic samples were collected prior to and 1, 2, 4, 8, 12, and 24 hours after letrozole dosing.
11. Summary of Plasma Letrozole Pharmacokinetic Parameter Following Letrozole Alone and in Combination With Palbociclib: Tmax at Phase 1 [ Time Frame: Cycle 2 Day 14, and Cycle 2 Day 28 ]
    On Cycle 2 Day 14, plasma pharmacokinetic samples for Palbociclib and letrozole were collected prior to and 1, 2, 4, 8, 12 and 24 hours after Palbociclib and letrozole dosing. On Cycle 2 Day 28, plasma pharmacokinetic samples were collected prior to and 1, 2, 4, 8, 12, and 24 hours after letrozole dosing.
12. Number of Participants With Increase From Baseline in Corrected QT (QTc) Interval at Phase 1 [ Time Frame: Cycle 1 Day 1 prior to dosing, Cycle 1 Day 14 (2, 4 [prior to meal], 8, 24, 48, and 96 hours after dosing of Palbociclib), Cycle 2 Day 1 and Day 14 (prior to and 4 hours after dosing of letrozole) ]
    Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR), by Bazette's formula (QTcB = QT divided by square root of RR) and corrected QT interval according to study-specific criteria (QTcS). Participants with maximum increase from baseline of 30 to less than (<) 60 msec(borderline) and greater than or equal to (>=) 60 msec (prolonged) were summarized.
13. Overall Survival (OS) at Phase 2 [ Time Frame: From randomization until death (assessed up to 86 months) ]
    Time in weeks or months from randomization to date of death due to any cause. OS was calculated as (the death date or last known alive date (if death date unavailable) minus the date of randomization plus 1) divided by 7 or 30.44 if in months.
14. Objective Response Rate - Percentage of Participants With Confirmed Objective Response at Phase 2- Investigator Assessment [ Time Frame: From randomization up to the end of treatment (approximately 41 months) ]
    Percentage of participants with objective response based assessment of confirmed CR or confirmed PR according to RECIST. Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. Per RECIST v1.0: CR defined as disappearance of all target lesions and non-target lesions. PR defined as ≥30% decrease in sum of the longest diameters (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST associated to non-progressive disease response for non target lesions.
15. Objective Response Rate - Percentage of Participants With Confirmed Objective Response in Participants With Measurable Disease at Phase 2- Investigator Assessment [ Time Frame: From randomization up to the end of treatment (approximately 41 months) ]
    Percentage of participants with objective response based assessment of confirmed CR or PR according to RECIST. Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. Per RECIST v1.0: CR defined as disappearance of all target lesions and non-target lesions. PR defined as ≥30% decrease in sum of the LD of the target lesions taking as a reference the baseline sum LD according to RECIST associated to non-progressive disease response for non target lesions. Measurable disease referred to the lesions that was accurately measured in at least 1 dimension (longest diameter to be recorded) as ≥20 mm with conventional techniques or as ≥10-16 mm with spiral computer tomography scan (depending on reconstruction interval). Clinical lesions were only be considered measurable when they were superficial (eg, skin nodules, palpable lymph nodes).
16. Duration of Response at Phase 2 - Investigator Assessment [ Time Frame: From randomization up to the end of treatment (approximately 41 months) ]
    Time in weeks, (months or years) from randomization or (start of study treatment for non-randomized studies) to first documentation of objective tumor progression. TTP was calculated as (first event date or last known progression-free date minus the date of randomization [or first dose of study medication for non-randomized studies] plus 1) divided by 7 or 30.44 if in months. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD] per RECIST).
17. Number of Participants With CBR at Phase 2 - Investigator Assessment [ Time Frame: From randomization up to the end of treatment (approximately 41 months) ]
    CBR is defined as a confirmed complete response (CR), confirmed partial response (PR), or stable disease (SD) for at least 24 weeks on study according to RECIST.
18. Time to Tumor Progression (TTP) at Phase 2-Investigator Assessment [ Time Frame: From randomization up to the end of treatment (approximately 41 months) ]
    Time in weeks, (months or years) from randomization or (start of study treatment for non-randomized studies) to first documentation of objective tumor progression. TTP was calculated as (first event date or last known progression-free date minus the date of randomization [or first dose of study medication for non-randomized studies] plus 1) divided by 7 or 30.44 if in months. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD] per RECIST).
19. Change From Baseline in Modified Brief Pain Inventory in Pain Severity Scale (mBPI-sf) Questionnaire at Phase 2 [ Time Frame: Baseline, End of treatment (approximately 41 months) ]
    The mBPI-sf is a validated and reliable self-report questionnaire which consists of 13 questions that assess the severity and impact of pain on daily function. The 13 items of the questionnaire make up two scales and two single items. The scales include the 4-item Pain Severity Scale (worst pain, least pain, average pain, and pain right now) and the 7-item Pain Interference Scale (general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life). Each item of the pain severity and pain interference scales are based on a 11-point numeric rating scale from 0 ("no pain" or "does not interfere") to 10 ("pain as bad as you can imagine" or "completely interferes").
20. Change From Baseline in Modified Brief Pain Inventory in Pain Interference Scale (mBPI-sf) Questionnaire at Phase 2 [ Time Frame: Baseline, End of treatment (approximately 41 months) ]
    The mBPI-sf is a validated and reliable self-report questionnaire which consists of 13 questions that assess the severity and impact of pain on daily function. The 13 items of the questionnaire make up two scales and two single items. The scales include the 4-item Pain Severity Scale (worst pain, least pain, average pain, and pain right now) and the 7-item Pain Interference Scale (general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life). Each item of the pain severity and pain interference scales are based on a 11-point numeric rating scale from 0 ("no pain" or "does not interfere") to 10 ("pain as bad as you can imagine" or "completely interferes").
21. Presence or Absence of Tumor Tissue Biomarkers at Phase 2 - p16/INK4A, CCND1 [ Time Frame: Screening visit (≤ 28 Days prior to dosing) ]
    Tissue samples were used for retrospective biomarker analyses. For Phase 2 Part 2, the tissue samples were sent to a central laboratory for the assessment of participant selection biomarkers. For Phase 2 Part 1, the assessment of the biomarkers (CCND1 amplification and/or loss of p16) were performed retrospectively from the available samples.
22. Presence or Absence of Tumor Tissue Biomarkers at Phase 2 - Ki67 [ Time Frame: Screening visit (≤ 28 Days prior to dosing) ]
    Frequency of tumor tissue biomarker Ki67 was evaluated in across treatment groups.
23. Presence or Absence of Tumor Tissue Biomarkers at Phase 2 - Tumor Retinoblastoma (RB) and CyclinD1 [ Time Frame: Screening visit (≤ 28 Days prior to dosing) ]
    Presence or absence of tumor RB and CyclinD1 were evaluated. The following definitions of expression applied in the below table: Positive: any expression >0 and Negative: any expression=0.
24. Summary of Copy Number for CCND1 (CCND1/CEP11) and p16/INK4A (p16/CEP9) at Phase 2 [ Time Frame: Screening visit (≤ 28 Days prior to dosing) ]
    Gene copy number for CCND1 (CCND1/CEP11) and p16/INK4A (p16/CEP9) were evaluated. This analysis was done for Phase 2 combined group.
25. Percentage of Participants With Tumor Expression of CYP19A1 and CCND1 Genotypes at Phase 2 [ Time Frame: Screening visit (≤ 28 Days prior to dosing) ]
    One 2-mL blood specimen was collected for the analysis of germline polymorphism in CYP19A1 and CCND1 genes. A single nucleotide polymorphism (SNP) rs4646 as defined in the National Center for Biotechnology Information (NCBI) database in the aromatase gene (CYP19A1) was analyzed. A germline polymorphism G/A870 (rs9344) in the CCND1 gene was analyzed.
26. Number of Participants With TEAEs (All Causalities) at Phase 2 [ Time Frame: Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) ]
    AE:any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship.AEs included both serious and non-serious AEs.SAE:AE resulting in any of following outcomes/deemed significant and jeopardized participants or required treatment to prevent other AE outcomes 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 AEs:events occurred between first dose of study drug and up to 28 days after last dose that were absent before treatment or worsened relative to pre-treatment state.AEs were graded as per the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 and coded using Medical Dictionary for Regulatory Activities (MedDRA). Participants with AE of grade 3 or 4 and grade 5 were reported as Grade 3:Severe, Grade 4:Life threatening, Grade 5:Death related to AE.
27. Number of Participants With Treatment-Related Adverse Events at Phase 2 [ Time Frame: Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) ]
    AE: any untoward medical occurrence in a participant who received study drug. AEs included both serious and non-serious adverse events. SAE: 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 AEs: events occurred between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. Treatment related AEs: all AEs with causality related to treatment. Relatedness to drug was assessed by the investigator. AEs were graded according to the CTCAE version 3.0 and coded using the MedDRA. Number of participants with AE of grade 3 or 4 and with AE of grade 5 were reported as Grade 3: Severe, Grade 4: Life threatening, Grade 5: Death related to AE.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Inoperable estrogen receptor positive and HER2 negative breast cancer.
• Postmenopausal status.
• Tumor tissue (archived acceptable) available for biomarker studies. For Phase 2 Part 2 - CCND1 amplification and/or loss of p16 as determined by the central laboratory.
• Acceptable bone marrow, liver and kidney function.

Exclusion Criteria:

• Prior or concomitant treatment for advanced breast cancer.
• Other major cancer in the past 3 years.
• Important cardiovascular events in the past 6 months.

Contacts and Locations

Locations

United States, California

Central Hematology Oncology Medical group Inc.

Alhambra, California, United States, 91801

UCLA Hematology/Oncology - Alhambra

Alhambra, California, United States, 91801

CBCC Global Research, Inc. at Comprehensive Blood and Cancer Center

Bakersfield, California, United States, 93309

St. Joseph Heritage Healthcare

Fullerton, California, United States, 92835

UCLA West Medical Pharmacy (Drug Management Only)

Los Angeles, California, United States, 90095-1772

UCLA West Medical Pharmacy

Los Angeles, California, United States, 90095-1772

Ronald Reagan UCLA Medical Center

Los Angeles, California, United States, 90095-6984

UCLA West Medical Pharmacy

Los Angeles, California, United States, 90095-7349

Drug Management Only: UCLA West Medical Pharmacy

Los Angeles, California, United States, 90095

Drug Management Only

Los Angeles, California, United States, 90095

Regulatory Managment

Los Angeles, California, United States, 90095

Ronald Reagan UCLA Medical Center

Los Angeles, California, United States, 90095

TORI -US Central Administration (Regulatory Management)

Los Angeles, California, United States, 90095

TORI -US Central Administration

Los Angeles, California, United States, 90095

TORI Central Administration (Regulatory Management)

Los Angeles, California, United States, 90095

TORI Central Administration (Regulatory Managment Only)

Los Angeles, California, United States, 90095

TRIO-US Central Administration

Los Angeles, California, United States, 90095

UCLA Hematology/Oncology

Los Angeles, California, United States, 90095

UCLA, Hematology/Oncology

Los Angeles, California, United States, 90095

Westwood Bowyer Clinic, Peter Morton Medical Building

Los Angeles, California, United States, 90095

Central Hematology Oncology Medical Group, Inc

Pasadena, California, United States, 91107

Torrance Health Association, DBA Torrance Memorial Physician Network/Cancer Care Associates

Redondo Beach, California, United States, 90277

Sansum Santa Barbara Medical Foundation Clinic

Santa Barbara, California, United States, 93105

Central Coast Medical Oncology Corporation

Santa Maria, California, United States, 93454

Santa Monica-UCLA Medical Center and Orthopaedic Hospital

Santa Monica, California, United States, 90404

UCLA Hematology Oncology-Santa Monica

Santa Monica, California, United States, 90404

UCLA Hematology/Oncology - Santa Clarita

Valencia, California, United States, 91355

United States, Georgia

Gwinnett Hospital System Inc.-d/b/a-The Center for Cancer Care

Duluth, Georgia, United States, 30096

Gwinnett Hospital System Inc.-d/b/a-The Center for Cancer Care

Lawrenceville, Georgia, United States, 30046

Gwinnett Hospital System Inc.-d/b/a-The Center for Cancer Care

Snellville, Georgia, United States, 30078

United States, Illinois

Illinois Cancer Specialists

Chicago, Illinois, United States, 60611

Resurrection Medical Group

Chicago, Illinois, United States, 60657

North Shore Oncology-Hematology Associates

Crystal Lake, Illinois, United States, 60014

North Shore Hematology Oncology

Highland Park, Illinois, United States, 60035

North Shore Oncology-Hematology Associates

Libertyville, Illinois, United States, 60048

North Shore Hematology Oncology

Skokie, Illinois, United States, 60077

United States, Nevada

Regulatory Office: Comprehensive Cancer Centers of Nevada

Henderson, Nevada, United States, 89014

Comprehensive Cancer Centers of Nevada

Henderson, Nevada, United States, 89052

Comprehensive Cancer Centers of Nevada

Henderson, Nevada, United States, 89074

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States, 89128

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States, 89148

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States, 89169

United States, Texas

Texas Oncology-Dallas Presbyterian Hospital

Dallas, Texas, United States, 75231

Texas Oncology-Baylor Charles A. Sammons Cancer Center

Dallas, Texas, United States, 75246

Investigational Products Center (IPC)

Fort Worth, Texas, United States, 76177

US Oncology Research and Clinical Pharmacy

Fort Worth, Texas, United States, 76177

United States, Virginia

Virginia Cancer Specialists, PC

Arlington, Virginia, United States, 22205

Virginia Cancer Specialists, PC

Fairfax, Virginia, United States, 22031

Virginia Cancer Specialists, PC

Gainesville, Virginia, United States, 20155

Virginia Cancer Specialists, PC

Leesburg, Virginia, United States, 20176

Virginia Cancer Specialists, PC

Woodbridge, Virginia, United States, 22191

Canada, British Columbia

BC Cancer Agency - Vancouver Centre

Vancouver, British Columbia, Canada, V5Z 4E6

Canada, Quebec

CSSS Champlain-Charles-Le Moyne Local HS-0054

Greenfield Park, Quebec, Canada, J4V 2H1

France

Centre Paul Papin, CRLCC

ANGERS Cedex 9, France, 49933

CHD Vendee

La Roche Sur Yon, France, 85925

Germany

Gemeinschaftspraxis, Onkologischer Schwerpunkt am Oskar-Helene-Heim

Berlin, Germany, 14195

Gemeinschaftspraxis Haematologie-Onkologie

Dresden, Germany, 01307

Martin-Luther-Universitaet Halle-Wittenberg

Halle/Saale, Germany, 06097

Universitaetsklinik und Poliklinik fuer Gynaekologie, Martin-Luther-Universitaet Halle-Wittenberg

Halle/Saale, Germany, 06120

Nationales Centrum fuer Tumorerkrankungen

Heidelberg, Germany, 69120

Frauenaerzte Pruener Gang Abts & Partner

Kiel, Germany, 24103

Klinik und Poliklinik fuer Frauenheilkunde und Geburtshilfe Universitaetsklinik Mainz

Mainz, Germany, 55101

Onkolog. Gemeinschaftspraxis

Muenchen, Germany, 80335

Frauenklinik vom Roten Kreuz

Muenchen, Germany, 80637

Frauenklinik und Poliklinik Klinikum rechts der Isar, Technische Universitaet Muenchen

Muenchen, Germany, 81675

Mutterhaus der Borromaeerinnen, Innere Medizin I

Trier, Germany, 54290

Hungary

Szent Margit Korhaz, Onkologia

Budapest, Hungary, 1032

Orszagos Onkologiai Intezet, Kemoterapia B

Budapest, Hungary, 1122

Fovarosi Onkormanyzat Uzsoki Utcai Korhaz

Budapest, Hungary, 1145

Petz Aladar Megyei Oktato Korhaz, Onkoradiologia

Gyor, Hungary, 9023

Borsod-Abauj-Zemplen Megyei Korhaz és Egyetemi Oktato Korhaz, Onkologia

Miskolc, Hungary, 3526

Szabolcs-Szatmar-Bereg Megyei Korhazak es

Nyiregyhaza, Hungary, 4400

Markusovszky Egyetemi Oktatokorhaz, Onkoradiologiai Osztaly

Szombathely, Hungary, 9700

Ireland

Bon Secours Hospital

Cork, Ireland

St. James's Hospital

Dublin 8, Ireland

St. Vincent's University Hospital

Dublin, Ireland, 4

Mater Misericordiae University Hospital

Dublin, Ireland, 7

Mater Private Hospital

Dublin, Ireland, 7

Italy

Divisione Oncologia Medica Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, IRST

Meldola, FC, Italy, 47014

M.O. di Oncologia - Azienda USL di Rimini - Ospedale "Cervesi"

Cattolica, Italy, 47841

Ospedale Civile di Faenza Centro Oncologico

Faenza, RA, Italy, 48018

Unita' Operativa di Oncologia, Ospedale Civile di Lugo

Lugo, RA, Italy, 48022

Ospedale Civile di Ravenna

Ravenna, Italy, 48100

Azienda Unita Sanitaria Locale di Rimini, U.O. di Oncologia ed Oncoematologia Ospedale degli Infermi

Rimini, Italy, 47900

Ospedale Villa San Pietro

Roma, Italy, 00189

Korea, Republic of

National Cancer Center, Center for Breast Cancer

Goyang-si, Gyeonggi-do, Korea, Republic of, 10408

Seoul National University Hospital

Seoul, Korea, Republic of, 03080

Samsung Medical Center

Seoul, Korea, Republic of, 135-710

Russian Federation

Federal State Budgetary Scientific Institution

Moscow, Russian Federation, 115478

Pyatigorsk Oncology Center

Pyatigorsk, Russian Federation, 357502

State Budgetary Healthcare Institution "Samara Regional Clinical Oncology Dispensary"

Samara, Russian Federation, 443031

Republican Clinical Oncology Dispensary of the Ministry of Health of Bashkortostan Republic

Ufa, Russian Federation, 450054

South Africa

Department of Oncotherapy, National Hospital

Bloemfontein, South Africa, 9301

Eastleigh Breast Care Centre

Pretoria, South Africa, 0041

Spain

Ico-Hospitalet

Hospitalet de Llobregat, Barcelona, Spain, 08907

Hospital General Universitario Vall D'Hebron

Barcelona, Spain, 08035

Centro Oncologico de Galicia

La Coruña, Spain, 15009

Hospital Universitario 12 de Octubre

Madrid, Spain, 28041

Hospital Universitario Virgen Del Rocio

Sevilla, Spain, 41013

Ukraine

Department of Oncology and Medical Radiology, SI "DMA of MOH, Ukraine, "MI "Dnipropetrovsk City

Dnipropetrovsk, Ukraine, 49102

Municipal Treatment-and-Prophylactic Institution 'Donetsk City Oncological Dispensary' Radiology dep

Donetsk, Ukraine, 83087

Municipal clinical treatment-and-propyilactic institution "Donetsk regional oncology center',

Donetsk, Ukraine, 83092

Kyiv City Clinical Oncologic Center

Kyiv, Ukraine, 03115

Lviv State Oncologic Regional Treatment and Diagnostic Centre

Lviv, Ukraine, 79031

Sponsors and Collaborators

Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

More Information

Additional Information:

To obtain contact information for a study center near you, click here. 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Finn RS, Rugo HS, Gelmon KA, Cristofanilli M, Colleoni M, Loi S, Schnell P, Lu DR, Theall KP, Mori A, Gauthier E, Bananis E, Turner NC, Dieras V. Long-Term Pooled Safety Analysis of Palbociclib in Combination with Endocrine Therapy for Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Updated Analysis with up to 5 Years of Follow-Up. Oncologist. 2021 May;26(5):e749-e755. doi: 10.1002/onco.13684. Epub 2021 Mar 10.

Finn RS, Boer K, Bondarenko I, Patel R, Pinter T, Schmidt M, Shparyk YV, Thummala A, Voitko N, Bananis E, McRoy L, Wilner K, Huang X, Kim S, Slamon DJ, Ettl J. Overall survival results from the randomized phase 2 study of palbociclib in combination with letrozole versus letrozole alone for first-line treatment of ER+/HER2- advanced breast cancer (PALOMA-1, TRIO-18). Breast Cancer Res Treat. 2020 Sep;183(2):419-428. doi: 10.1007/s10549-020-05755-7. Epub 2020 Jul 18.

Ettl J, Im SA, Ro J, Masuda N, Colleoni M, Schnell P, Bananis E, Lu DR, Cristofanilli M, Rugo HS, Finn RS. Hematologic adverse events following palbociclib dose reduction in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: pooled analysis from randomized phase 2 and 3 studies. Breast Cancer Res. 2020 Mar 12;22(1):27. doi: 10.1186/s13058-020-01263-0.

Rugo HS, Turner NC, Finn RS, Joy AA, Verma S, Harbeck N, Masuda N, Im SA, Huang X, Kim S, Sun W, Iyer S, Schnell P, Bartlett CH, Johnston S. Palbociclib plus endocrine therapy in older women with HR+/HER2- advanced breast cancer: a pooled analysis of randomised PALOMA clinical studies. Eur J Cancer. 2018 Sep;101:123-133. doi: 10.1016/j.ejca.2018.05.017. Epub 2018 Jul 25.

Dieras V, Rugo HS, Schnell P, Gelmon K, Cristofanilli M, Loi S, Colleoni M, Lu DR, Mori A, Gauthier E, Huang Bartlett C, Slamon DJ, Turner NC, Finn RS. Long-term Pooled Safety Analysis of Palbociclib in Combination With Endocrine Therapy for HR+/HER2- Advanced Breast Cancer. J Natl Cancer Inst. 2019 Apr 1;111(4):419-430. doi: 10.1093/jnci/djy109.

Wedam SB, Beaver JA, Amiri-Kordestani L, Bloomquist E, Tang S, Goldberg KB, Sridhara R, Ibrahim A, Kim G, Kluetz P, McKee A, Pazdur R. US Food and Drug Administration Pooled Analysis to Assess the Impact of Bone-Only Metastatic Breast Cancer on Clinical Trial Outcomes and Radiographic Assessments. J Clin Oncol. 2018 Apr 20;36(12):1225-1231. doi: 10.1200/JCO.2017.74.6917. Epub 2018 Mar 9.

Bell T, Crown JP, Lang I, Bhattacharyya H, Zanotti G, Randolph S, Kim S, Huang X, Huang Bartlett C, Finn RS, Slamon D. Impact of palbociclib plus letrozole on pain severity and pain interference with daily activities in patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer as first-line treatment. Curr Med Res Opin. 2016 May;32(5):959-65. doi: 10.1185/03007995.2016.1157060. Epub 2016 Mar 2.

Finn RS, Crown JP, Lang I, Boer K, Bondarenko IM, Kulyk SO, Ettl J, Patel R, Pinter T, Schmidt M, Shparyk Y, Thummala AR, Voytko NL, Fowst C, Huang X, Kim ST, Randolph S, Slamon DJ. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol. 2015 Jan;16(1):25-35. doi: 10.1016/S1470-2045(14)71159-3. Epub 2014 Dec 16.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00721409
• Other Study ID Numbers: A5481003; 2008-002392-27 ( EudraCT Number )
• First Posted: July 24, 2008
• Results First Posted: March 19, 2015
• Last Update Posted: November 4, 2019
• Last Verified: October 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
• URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

Keywords provided by Pfizer:

hormone-receptor positive advanced breast cancer

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Letrozole; Palbociclib; Antineoplastic Agents; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Protein Kinase Inhibitors