Palbociclib Plus Letrozole For Postmenopausal Women With HR(+) HER2(-) Advanced Breast Cancer For Whom Letrozole Is Deemed Appropriate

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02600923
• Collaborator: (none)
• Enrollment: 131
• Locations: 24
• Arm: 1
• Actual Duration (Months): 37.4
• Patients Per Site: 5.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to provide access to palbociclib in Mexico and in selected Latin American countries before it becomes commercially available to patients with HR positive/HER2-negative ABC who are appropriate candidates for letrozole therapy.

Condition or Disease	Intervention/Treatment	Phase
Advanced Breast Cancer Female	Drug: Palbociclib; Drug: Letrozole	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 131 participants
• Allocation: N/A
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: STUDY OF PALBOCICLIB IN COMBINATION WITH LETROZOLE AS TREATMENT OF POSTMENOPAUSAL WOMEN WITH HORMONE RECEPTOR POSITIVE, HER2-NEGATIVE ADVANCED BREAST CANCER FOR WHOM LETROZOLE THERAPY IS DEEMED APPROPRIATE
• Actual Study Start Date: Apr 15, 2016
• Actual Primary Completion Date: May 28, 2019
• Actual Study Completion Date: May 28, 2019

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Palbociclib + Letrozole palbociclib and letrozole combination

Drug: Palbociclib; Palbociclib will be administered orally once a day at 125 mg/day for 21 days followed by 7 days off treatment for each 28-day cycle (Schedule 3/1).; Other Names: Ibrance ; Drug: Letrozole; Letrozole will be administered orally at 2.5 mg once daily as continuous daily dosing schedule according to product labeling and in compliance with its local prescribing information.; Other Names: Femara

Outcome Measures

Primary Outcome Measures

1. Number of Participants With All-causality Treatment-emergent Adverse Events (TEAEs) [3 years]

   An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. All AEs reported after initiation of study drug treatment were considered as TEAE. AE severity was graded according to Common Terminology Criteria for AEs (CTCAE) version 4.03. Grade 1 AEs are mild AEs; Grade 2 AEs are moderate AEs; Grade 3 AEs are severe AEs, Grade 4 AEs are life-threatening consequences and Grade 5 AEs are deaths related to AEs. Each AE was counted once for the participant in the most severe severity.

2. Number of Participants With Palbociclib-related TEAEs [3 years]

   An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. All AEs reported after initiation of study drug treatment were considered as TEAE. AE severity was graded according to CTCAE version 4.03. Grade 1 AEs are mild AEs; Grade 2 AEs are moderate AEs; Grade 3 AEs are severe AEs, Grade 4 AEs are life-threatening consequences and Grade 5 AEs are deaths related to AEs. Palbociclib-related TEAEs were determined by the investigator.

3. Number of Participants With Serious Adverse Events (SAEs) [3 years]

   An SAE was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. AEs included both SAEs and AEs. Palbociclib-related SAEs were determined by the investigator.

Secondary Outcome Measures

1. Number of Participants With Death [3 years]

   Death from any cause while on treatment and within 28 days of palbociclib discontinuation was only counted below.

2. The Objective Response Rate (ORR) [3 years]

   The tumor response was based on the response reported by investigator per local practice. No response confirmation was applied. ORR was defined as the percentage of participants with complete response or partial response relative to all as-treated population.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Adult women with proven diagnosis of advanced adenocarcinoma of the breast (locoregional recurrent or metastatic disease).

• Women who are not of childbearing potential.

• ER-positive and/or Progesterone receptor (PgR)-positive tumor based on local laboratory results (test as per local practice).

• HER2-negative breast cancer based on local laboratory results (test as per local practice or local guidelines).

• Patients must be appropriate candidates for letrozole therapy.

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

• Adequate bone marrow function.

• Adequate liver function

• Adequate renal function.

Exclusion Criteria:

• Known hypersensitivity to letrozole, or any of its excipients, or to any palbociclib excipients.

• Current use of food or drugs known to be potent inhibitors or inducers of CYP3A4 isoenzymes within 7 days prior to study entry.

• Prior treatment with any CDK inhibitor.

• Previous participation in a palbociclib clinical study.

• Participation in other studies involving investigational drug(s) within 2 weeks prior to study entry and/or during study participation.

• QTc >480 msec; history of QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes.

• High cardiovascular risk, including, but not limited to recent myocardial infarction, severe/unstable angina and severe cardiac dysrhythmias in the past 6 months prior to enrollment.

• Diagnosis of any second invasive malignancy within the last 3 years prior to enrollment. Note: patients with adequately treated basal cell or squamous cell skin cancer, a history of intraepithelial neoplasia or in situ disease (eg, carcinoma in situ of the cervix or melanoma in situ) may enter.

• Active uncontrolled or symptomatic brain metastases. Previously treated and clinically stable, brain metastases are permitted.

• Other severe acute or chronic medical or psychiatric conditions.

• Patients who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or patients who are Pfizer employees directly involved in the conduct of the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Instituto de Oncologia de Rosario	Rosario	Santa FE	Argentina	S2000KZE
2	Sanatorio Guemes	Caba		Argentina	C1180AAX
3	Hospital Italiano de Buenos Aires	Caba		Argentina	C1181ACH
4	Hospital Britanico de Buenos Aires	Caba		Argentina	C1280AEB
5	Instituto Medico Especializado Alexander Fleming	Caba		Argentina	C1426ANZ
6	Instituto de Cardiologia y Cirugia Cardiovascular	Santa Fe		Argentina	S3000EPV
7	ISIS Centro Especializado	Santa Fe		Argentina	S3000FFU
8	Hospital Da Cidade De Passo Fundo	Passo Fundo	RIO Grande DO SUL	Brazil	99010-260
9	Hospital Sao Lucas da PUCRS / Uniao Brasileira de Educacao e Assistencia	Porto Alegre	RIO Grande DO SUL	Brazil	90610-000
10	Oncologia Rede D'Or S.A.	Rio de Janeiro		Brazil	22271-110
11	IDOR - Instituto D'Or em Pesquisa e Ensino	Rio de Janeiro		Brazil	22281-100
12	Sociedade Beneficente de Senhoras Hospital Sirio Libanes	Sao Paulo		Brazil	01308-050
13	Clínica de Pesquisa e Centro de Estudos em Oncologia Ginecológica e Mamária Ltda	São Paulo		Brazil	01317-000
14	Instituto de Cancerologia S.A.	Medellin	Antioquia	Colombia	050034
15	Oncomedica S.A.	Monteria	Cordoba	Colombia	230003
16	Administradora Country	Bogota	Distrito Capital	Colombia	11001000
17	Oncology Center	Bogota	Distrito Capital	Colombia	110221162
18	Imagenes Diagnosticas	Pereira	Risaralda	Colombia	660001
19	ONCOLOGOS DEL OCCIDENTE S.A.S Sede Pereira Clinica de Alta Tecnologia Maraya	Pereira	Risaralda	Colombia	660001
20	Fucam A.C.	Coyoacan	D.f.	Mexico	04890
21	Instituto Nacional de Cancerologia	Tlalpan	D.f.	Mexico	14080
22	Hospital Maria Auxiliadora	Guadalajara	Jalisco	Mexico	44540
23	Clinica de Especialidades Medicas Intepro, ONCE Oncologia Especializada	Zapopan	Jalisco	Mexico	45030
24	Hospital Universitario Dr. Jose Eleuterio Gonzalez	Monterrey	Nuevo LEON	Mexico	64460

Sponsors and Collaborators

• Pfizer

Investigators

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

Study Documents (Full-Text)

• Study Protocol - Jul 23, 2015
• Statistical Analysis Plan - Feb 4, 2016

More Information

Additional Information:

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

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT02600923
• Other Study ID Numbers: A5481053
• First Posted: Nov 9, 2015
• Last Update Posted: Jan 20, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Pfizer: palbociclib, ibrance, breast cancer
• Additional relevant MeSH terms: Breast Neoplasms; Letrozole; Palbociclib

Study Results

Participant Flow

Pre-assignment Detail	A total of 131 participants were enrolled and assigned to study treatment, and 130 participants were treated in the study.

Arm/Group Title	Palbociclib+Letrozole
Arm/Group Description	Participants received palbociclib orally once daily at 125 mg for 21 days followed by 7 days off treatment for each 28-day cycle, and letrozole orally at 2.5 mg QD as a continuous daily dosing schedule. Participants continued to receive treatments with palbociclib+letrozole until disease progression, symptomatic deterioration, unacceptable toxicity, death, withdrawal of consent, or time of commercial availability of palbociclib, whichever occurred first.
Period Title: Overall Study
STARTED	131
Treated	130
COMPLETED	0
NOT COMPLETED	131

Baseline Characteristics

Arm/Group Title	Palbociclib+Letrozole
Arm/Group Description	Participants received palbociclib orally once daily at 125 mg for 21 days followed by 7 days off treatment for each 28-day cycle, and letrozole orally at 2.5 mg QD as a continuous daily dosing schedule. Participants continued to receive treatments with palbociclib+letrozole until disease progression, symptomatic deterioration, unacceptable toxicity, death, withdrawal of consent, or time of commercial availability of palbociclib, whichever occurred first.
Overall Participants	130
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	89 68.5%
>=65 years	41 31.5%
Sex: Female, Male (Count of Participants)
Female	130 100%
Male	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	130 100%
Not Hispanic or Latino	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With All-causality Treatment-emergent Adverse Events (TEAEs)
Description	An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. All AEs reported after initiation of study drug treatment were considered as TEAE. AE severity was graded according to Common Terminology Criteria for AEs (CTCAE) version 4.03. Grade 1 AEs are mild AEs; Grade 2 AEs are moderate AEs; Grade 3 AEs are severe AEs, Grade 4 AEs are life-threatening consequences and Grade 5 AEs are deaths related to AEs. Each AE was counted once for the participant in the most severe severity.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who received at least 1 dose of palbociclib treatment.

Arm/Group Title	Palbociclib+Letrozole
Arm/Group Description	Participants received palbociclib orally once daily at 125 mg for 21 days followed by 7 days off treatment for each 28-day cycle, and letrozole orally at 2.5 mg QD as a continuous daily dosing schedule. Participants continued to receive treatments with palbociclib+letrozole until disease progression, symptomatic deterioration, unacceptable toxicity, death, withdrawal of consent, or time of commercial availability of palbociclib, whichever occurred first.
Measure Participants	130
Grade 1	0 0%
Grade 2	17 13.1%
Grade 3	82 63.1%
Grade 4	23 17.7%
Grade 5	7 5.4%

2. Primary Outcome

Title	Number of Participants With Palbociclib-related TEAEs
Description	An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. All AEs reported after initiation of study drug treatment were considered as TEAE. AE severity was graded according to CTCAE version 4.03. Grade 1 AEs are mild AEs; Grade 2 AEs are moderate AEs; Grade 3 AEs are severe AEs, Grade 4 AEs are life-threatening consequences and Grade 5 AEs are deaths related to AEs. Palbociclib-related TEAEs were determined by the investigator.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who received at least 1 dose of palbociclib treatment.

Arm/Group Title	Palbociclib+Letrozole
Arm/Group Description	Participants received palbociclib orally once daily at 125 mg for 21 days followed by 7 days off treatment for each 28-day cycle, and letrozole orally at 2.5 mg QD as a continuous daily dosing schedule. Participants continued to receive treatments with palbociclib+letrozole until disease progression, symptomatic deterioration, unacceptable toxicity, death, withdrawal of consent, or time of commercial availability of palbociclib, whichever occurred first.
Measure Participants	130
Grade 1	2 1.5%
Grade 2	25 19.2%
Grade 3	81 62.3%
Grade 4	20 15.4%
Grade 5	0 0%

3. Primary Outcome

Title	Number of Participants With Serious Adverse Events (SAEs)
Description	An SAE was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. AEs included both SAEs and AEs. Palbociclib-related SAEs were determined by the investigator.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who received at least 1 dose of palbociclib treatment.

Arm/Group Title	Palbociclib+Letrozole
Arm/Group Description	Participants received palbociclib orally once daily at 125 mg for 21 days followed by 7 days off treatment for each 28-day cycle, and letrozole orally at 2.5 mg QD as a continuous daily dosing schedule. Participants continued to receive treatments with palbociclib+letrozole until disease progression, symptomatic deterioration, unacceptable toxicity, death, withdrawal of consent, or time of commercial availability of palbociclib, whichever occurred first.
Measure Participants	130
All-causality	32 24.6%
Palbociclib-related	6 4.6%

4. Secondary Outcome

Title	Number of Participants With Death
Description	Death from any cause while on treatment and within 28 days of palbociclib discontinuation was only counted below.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who received at least 1 dose of palbociclib treatment.

Arm/Group Title	Palbociclib+Letrozole
Arm/Group Description	Participants received palbociclib orally once daily at 125 mg for 21 days followed by 7 days off treatment for each 28-day cycle, and letrozole orally at 2.5 mg QD as a continuous daily dosing schedule. Participants continued to receive treatments with palbociclib+letrozole until disease progression, symptomatic deterioration, unacceptable toxicity, death, withdrawal of consent, or time of commercial availability of palbociclib, whichever occurred first.
Measure Participants	130
Count of Participants [Participants]	5 3.8%

5. Secondary Outcome

Title	The Objective Response Rate (ORR)
Description	The tumor response was based on the response reported by investigator per local practice. No response confirmation was applied. ORR was defined as the percentage of participants with complete response or partial response relative to all as-treated population.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

The analysis population included participants with efficacy data contributing to the analysis.

Arm/Group Title	Palbociclib+Letrozole
Arm/Group Description	Participants received palbociclib orally once daily at 125 mg for 21 days followed by 7 days off treatment for each 28-day cycle, and letrozole orally at 2.5 mg QD as a continuous daily dosing schedule. Participants continued to receive treatments with palbociclib+letrozole until disease progression, symptomatic deterioration, unacceptable toxicity, death, withdrawal of consent, or time of commercial availability of palbociclib, whichever occurred first.
Measure Participants	129
Number (95% Confidence Interval) [percentage of evaluable participants]	24.8 19.1%

Adverse Events

Time Frame	3 years
Adverse Event Reporting Description	The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another participant, or 1 participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Arm/Group Title	Palbociclib+Letrozole
Arm/Group Description	Participants received palbociclib orally once daily at 125 mg for 21 days followed by 7 days off treatment for each 28-day cycle, and letrozole orally at 2.5 mg QD as a continuous daily dosing schedule. Participants continued to receive treatments with palbociclib+letrozole until disease progression, symptomatic deterioration, unacceptable toxicity, death, withdrawal of consent, or time of commercial availability of palbociclib, whichever occurred first.
All Cause Mortality
	Palbociclib+Letrozole
	Affected / at Risk (%)	# Events
Total	10/130 (7.7%)
Serious Adverse Events
	Palbociclib+Letrozole
	Affected / at Risk (%)	# Events
Total	32/130 (24.6%)
Blood and lymphatic system disorders
Anaemia	1/130 (0.8%)	1
Febrile neutropenia	1/130 (0.8%)	1
Neutropenia	1/130 (0.8%)	2
Pancytopenia	1/130 (0.8%)	1
Cardiac disorders
Arteriosclerosis coronary artery	1/130 (0.8%)	1
Gastrointestinal disorders
Ascites	1/130 (0.8%)	1
General disorders
Chest pain	1/130 (0.8%)	1
Disease progression	2/130 (1.5%)	2
General physical health deterioration	1/130 (0.8%)	1
Infections and infestations
Cellulitis	1/130 (0.8%)	1
Device related infection	1/130 (0.8%)	1
Herpes virus infection	1/130 (0.8%)	1
Pneumonia	3/130 (2.3%)	3
Tuberculosis	2/130 (1.5%)	2
Urinary tract infection	1/130 (0.8%)	1
Injury, poisoning and procedural complications
Femur fracture	2/130 (1.5%)	2
Fractured ischium	1/130 (0.8%)	1
Road traffic accident	1/130 (0.8%)	1
Investigations
Platelet count decreased	1/130 (0.8%)	1
Metabolism and nutrition disorders
Hypoglycaemia	1/130 (0.8%)	1
Musculoskeletal and connective tissue disorders
Back pain	2/130 (1.5%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression	1/130 (0.8%)	1
Malignant pleural effusion	1/130 (0.8%)	1
Neoplasm progression	1/130 (0.8%)	1
Tumour flare	1/130 (0.8%)	1
Nervous system disorders
Cerebrovascular accident	1/130 (0.8%)	1
Haemorrhagic stroke	1/130 (0.8%)	1
Hypertensive hydrocephalus	1/130 (0.8%)	1
Ischaemic stroke	1/130 (0.8%)	1
Spinal cord compression	1/130 (0.8%)	1
Respiratory, thoracic and mediastinal disorders
Pleural effusion	1/130 (0.8%)	1
Pulmonary embolism	1/130 (0.8%)	1
Respiratory failure	1/130 (0.8%)	1
Skin and subcutaneous tissue disorders
Skin ulcer	1/130 (0.8%)	1
Vascular disorders
Deep vein thrombosis	2/130 (1.5%)	3
Vena cava thrombosis	1/130 (0.8%)	1
Other (Not Including Serious) Adverse Events
	Palbociclib+Letrozole
	Affected / at Risk (%)	# Events
Total	129/130 (99.2%)
Blood and lymphatic system disorders
Anaemia	44/130 (33.8%)	111
Leukopenia	45/130 (34.6%)	173
Lymphopenia	11/130 (8.5%)	19
Neutropenia	91/130 (70%)	709
Thrombocytopenia	32/130 (24.6%)	89
Gastrointestinal disorders
Abdominal distension	14/130 (10.8%)	21
Abdominal pain	12/130 (9.2%)	17
Abdominal pain upper	8/130 (6.2%)	8
Constipation	21/130 (16.2%)	24
Diarrhoea	30/130 (23.1%)	50
Dyspepsia	9/130 (6.9%)	10
Nausea	25/130 (19.2%)	34
Stomatitis	8/130 (6.2%)	15
Vomiting	17/130 (13.1%)	40
General disorders
Asthenia	22/130 (16.9%)	33
Fatigue	20/130 (15.4%)	26
Mucosal inflammation	11/130 (8.5%)	26
Oedema peripheral	9/130 (6.9%)	12
Pyrexia	8/130 (6.2%)	9
Infections and infestations
Influenza	10/130 (7.7%)	11
Nasopharyngitis	7/130 (5.4%)	14
Upper respiratory tract infection	15/130 (11.5%)	21
Urinary tract infection	7/130 (5.4%)	8
Investigations
Lymphocyte count decreased	16/130 (12.3%)	62
Neutrophil count decreased	36/130 (27.7%)	259
Platelet count decreased	19/130 (14.6%)	50
White blood cell count decreased	23/130 (17.7%)	129
Metabolism and nutrition disorders
Decreased appetite	10/130 (7.7%)	10
Musculoskeletal and connective tissue disorders
Arthralgia	26/130 (20%)	31
Back pain	21/130 (16.2%)	33
Myalgia	8/130 (6.2%)	10
Pain in extremity	15/130 (11.5%)	23
Nervous system disorders
Dizziness	12/130 (9.2%)	14
Headache	25/130 (19.2%)	37
Psychiatric disorders
Insomnia	9/130 (6.9%)	9
Respiratory, thoracic and mediastinal disorders
Cough	21/130 (16.2%)	25
Dyspnoea	8/130 (6.2%)	10
Skin and subcutaneous tissue disorders
Alopecia	18/130 (13.8%)	22
Dry skin	10/130 (7.7%)	10
Pruritus	7/130 (5.4%)	7
Rash	10/130 (7.7%)	13

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.