Palbociclib / Letrozole or Fulvestrant in African American Women With HR+ HER2- Breast Cancer (PALINA)
7 de septiembre de 2021 actualizado por: Georgetown University
Phase II Safety Study of Palbociclib in Combination With Letrozole or Fulvestrant in African American Women With Hormone Receptor Positive HER2 Negative Advanced Breast Cancer
This study aims to evaluate the hematological safety of palbociclib with letrozole and fulvestrant in African American women with hormone receptor positive HER2 negative advanced breast cancer.
Hematological safety is a composite endpoint of episodes of febrile neutropenia and treatment discontinuation due to neutropenia according to current recommendations for management of neutropenia
Descripción general del estudio
Estado
Terminado
Intervención / Tratamiento
Descripción detallada
The study is designed to assess the rate of completion of planned oncology therapy in the absence of a hematological event defined as episodes of febrile neutropenia and treatment discontinuation due to neutropenia. A completion rate of 80% is considered of clinical relevance as to benefit breast cancer patients who are at a higher risk of having ethnic neutropenia where as a completion rate of 60% is considered poor and to justify additional safety studies. A two stage design with a total of 35 patients is used to test if the completion rate is at least 80% versus if it is below 60% with 80% power at a significance level of 5%.
An exact confidence interval of the completion rate will be calculated. Investigators estimate there will be no more than a 10% rate of febrile neutropenia. Due to the small sample size, the analysis of secondary endpoints will be descriptive and will not include specific hypothesis testing.
Tipo de estudio
Intervencionista
Inscripción (Actual)
35
Fase
- Fase 2
- Fase 3
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
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District of Columbia
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Washington, District of Columbia, Estados Unidos, 20007
- MedStar Georgetown University Hospital
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Washington, District of Columbia, Estados Unidos, 20013
- MedStar Washington Hospital Center
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Illinois
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Chicago, Illinois, Estados Unidos, 60637
- University of Chicago
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Maryland
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Baltimore, Maryland, Estados Unidos, 21218
- MedStar Union Memorial Hospital
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Baltimore, Maryland, Estados Unidos, 21239
- MedStar Good Samaritan Hospital
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Pennsylvania
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Philadelphia, Pennsylvania, Estados Unidos, 19107
- Thomas Jefferson University
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
18 años y mayores (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Femenino
Descripción
Inclusion Criteria:
- Self-identified Black, African or African American women of ≥ 18 years of age with proven diagnosis of advanced adenocarcinoma of the breast (locoregionally recurrent or metastatic disease)
- ER-positive and/or PgR-positive tumor based on local laboratory results
- HER2-negative breast cancer based on local laboratory results (test to be used as per local practice)
- Patients must be appropriate candidates for letrozole or fulvestrant therapy
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Adequate bone marrow function:
- Absolute Neutrophil Count (ANC) ≥ 1,000/mm3 (1.0 x 109/L);
- Platelets ≥100,000/mm3 (100 x 109/L);
- Hemoglobin ≥9 g/dL (90 g/L).
Exclusion Criteria:
- Current use of food or drugs known to be potent inhibitors or inducers of CYP3A4
- Active uncontrolled or symptomatic brain metastases. Previously treated and clinically stable, as per Investigator's judgment, brain metastases are permitted.
Previous CDK4/6 inhibitor
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Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Experimental: Palbociclib + Letrozole or Fulvestrant
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Palbociclib x 21 days with a 7 day rest plus 2.5 mg Letrozole QD (no break) or Fulvestrant 500mg IM every 2 weeks for 3 doses and then every 4 weeks until progression or maximum of 12 months
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Number of Patients Who Complete Planned Oncologic Therapy Without the Development of a Hematological Event
Periodo de tiempo: 12 months
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For study purpose febrile neutropenia will be defined according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0: "ANC less than 1000/mm3 with a single temperature of >38.3 degrees Celsius (101 degrees Fahrenheit) or a sustained temperature of 38 degrees Celsius (100.4 degrees Fahrenheit) for more than one hour." Planned oncology therapy is defined as completion of one year of therapy for advanced breast cancer in the absence of disease progression or cessation of study drug due to progressive disease or non-hematological toxicity. |
12 months
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Dose Delays in Palbociclib Attributed to Neutropenia
Periodo de tiempo: 12 months
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Number of patients who required dose delays in palbociclib attributed to neutropenia.
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12 months
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Dose Reductions in Palbociclib Therapy Attributed to Neutropenia
Periodo de tiempo: 12 months
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Number of patients who required dose reductions in palbociclib therapy
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12 months
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Clinical Benefit Rate
Periodo de tiempo: 24 weeks
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Clinical Benefit Rate (CBR), for those with evaluable disease, defined as the percentage of patients who achieved complete response, partial response and stable disease.
RECIST 1.1 was used as the standard way to measure response to treatment.
The mean (SD) of specific metabolites were calculated at each time point and graphically assess these measures over time with clinical response and hematological toxicity.
The mean change in these variables from baseline to each follow-up point was be calculated.
Generalized linear model was utilized for the correlative analysis of clinical response and hematologic events.
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24 weeks
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Investigadores
- Investigador principal: Claudine Isaacs, MD, MedStar Georgetown University Hospital
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Publicaciones Generales
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- Turner NC, Huang Bartlett C, Cristofanilli M. Palbociclib in Hormone-Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2015 Oct 22;373(17):1672-3. doi: 10.1056/NEJMc1510345. No abstract available.
- Finn RS, Dering J, Conklin D, Kalous O, Cohen DJ, Desai AJ, Ginther C, Atefi M, Chen I, Fowst C, Los G, Slamon DJ. PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro. Breast Cancer Res. 2009;11(5):R77. doi: 10.1186/bcr2419.
- Wood WC, Muss HB, Solin LJ, Olopade OI. Malignant Tumors of the Breast. In: DeVita VT Jr, Hellmann S, Rosenberg SA, editors. Cancer, Principle and Practice of Oncology, 7thEdition, Lippincott Williams and Wilkins; 2005; 1415-1477.
- Leung BS, Potter AH. Mode of estrogen action on cell proliferation in CAMA-1 cells: II. Sensitivity of G1 phase population. J Cell Biochem. 1987 Jul;34(3):213-25. doi: 10.1002/jcb.240340307.
- Sutherland RL, Hall RE, Taylor IW. Cell proliferation kinetics of MCF-7 human mammary carcinoma cells in culture and effects of tamoxifen on exponentially growing and plateau-phase cells. Cancer Res. 1983 Sep;43(9):3998-4006.
- Mouridsen H, Gershanovich M, Sun Y, Perez-Carrion R, Boni C, Monnier A, Apffelstaedt J, Smith R, Sleeboom HP, Jaenicke F, Pluzanska A, Dank M, Becquart D, Bapsy PP, Salminen E, Snyder R, Chaudri-Ross H, Lang R, Wyld P, Bhatnagar A. Phase III study of letrozole versus tamoxifen as first-line therapy of advanced breast cancer in postmenopausal women: analysis of survival and update of efficacy from the International Letrozole Breast Cancer Group. J Clin Oncol. 2003 Jun 1;21(11):2101-9. doi: 10.1200/JCO.2003.04.194.
- Schwartz GK, LoRusso PM, Dickson MA, Randolph SS, Shaik MN, Wilner KD, Courtney R, O'Dwyer PJ. Phase I study of PD 0332991, a cyclin-dependent kinase inhibitor, administered in 3-week cycles (Schedule 2/1). Br J Cancer. 2011 Jun 7;104(12):1862-8. doi: 10.1038/bjc.2011.177. Epub 2011 May 24.
- Flaherty KT, Lorusso PM, Demichele A, Abramson VG, Courtney R, Randolph SS, Shaik MN, Wilner KD, O'Dwyer PJ, Schwartz GK. Phase I, dose-escalation trial of the oral cyclin-dependent kinase 4/6 inhibitor PD 0332991, administered using a 21-day schedule in patients with advanced cancer. Clin Cancer Res. 2012 Jan 15;18(2):568-76. doi: 10.1158/1078-0432.CCR-11-0509. Epub 2011 Nov 16.
- DeMichele A, Clark AS, Tan KS, Heitjan DF, Gramlich K, Gallagher M, Lal P, Feldman M, Zhang P, Colameco C, Lewis D, Langer M, Goodman N, Domchek S, Gogineni K, Rosen M, Fox K, O'Dwyer P. CDK 4/6 inhibitor palbociclib (PD0332991) in Rb+ advanced breast cancer: phase II activity, safety, and predictive biomarker assessment. Clin Cancer Res. 2015 Mar 1;21(5):995-1001. doi: 10.1158/1078-0432.CCR-14-2258. Epub 2014 Dec 11.
- A study of Palbociclib (PD-0332991) + letrozole vs. letrozole for first line treatment of postmenopausal women with ER/HER2- advanced breast cancer (PALOMA-2). Available at: https://clinicaltrials.gov/ct2/show/NCT01740427. Accessed on August 9, 2015
- NIH Policy and Guidelines on The Inclusion of Women and Minorities as Subjects in Clinical Research - Amended, October, 2001
- Chen MS Jr, Lara PN, Dang JH, Paterniti DA, Kelly K. Twenty years post-NIH Revitalization Act: enhancing minority participation in clinical trials (EMPaCT): laying the groundwork for improving minority clinical trial accrual: renewing the case for enhancing minority participation in cancer clinical trials. Cancer. 2014 Apr 1;120 Suppl 7(0 7):1091-6. doi: 10.1002/cncr.28575.
- Hsieh MM, Everhart JE, Byrd-Holt DD, Tisdale JF, Rodgers GP. Prevalence of neutropenia in the U.S. population: age, sex, smoking status, and ethnic differences. Ann Intern Med. 2007 Apr 3;146(7):486-92. doi: 10.7326/0003-4819-146-7-200704030-00004.
- Reich D, Nalls MA, Kao WH, Akylbekova EL, Tandon A, Patterson N, Mullikin J, Hsueh WC, Cheng CY, Coresh J, Boerwinkle E, Li M, Waliszewska A, Neubauer J, Li R, Leak TS, Ekunwe L, Files JC, Hardy CL, Zmuda JM, Taylor HA, Ziv E, Harris TB, Wilson JG. Reduced neutrophil count in people of African descent is due to a regulatory variant in the Duffy antigen receptor for chemokines gene. PLoS Genet. 2009 Jan;5(1):e1000360. doi: 10.1371/journal.pgen.1000360. Epub 2009 Jan 30.
- Hsieh MM, Tisdale JF, Rodgers GP, Young NS, Trimble EL, Little RF. Neutrophil count in African Americans: lowering the target cutoff to initiate or resume chemotherapy? J Clin Oncol. 2010 Apr 1;28(10):1633-7. doi: 10.1200/JCO.2009.24.3881. Epub 2010 Mar 1. No abstract available.
- Hershman D, Weinberg M, Rosner Z, Alexis K, Tiersten A, Grann VR, Troxel A, Neugut AI. Ethnic neutropenia and treatment delay in African American women undergoing chemotherapy for early-stage breast cancer. J Natl Cancer Inst. 2003 Oct 15;95(20):1545-8. doi: 10.1093/jnci/djg073.
- Shajahan-Haq AN, Cheema MS, Clarke R. Application of metabolomics in drug resistant breast cancer research. Metabolites. 2015 Feb 16;5(1):100-18. doi: 10.3390/metabo5010100.
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- Asiago VM, Alvarado LZ, Shanaiah N, Gowda GA, Owusu-Sarfo K, Ballas RA, Raftery D. Early detection of recurrent breast cancer using metabolite profiling. Cancer Res. 2010 Nov 1;70(21):8309-18. doi: 10.1158/0008-5472.CAN-10-1319. Epub 2010 Oct 19.
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- Yu DD, Wu Y, Zhang XH, Lv MM, Chen WX, Chen X, Yang SJ, Shen H, Zhong SL, Tang JH, Zhao JH. Exosomes from adriamycin-resistant breast cancer cells transmit drug resistance partly by delivering miR-222. Tumour Biol. 2016 Mar;37(3):3227-35. doi: 10.1007/s13277-015-4161-0. Epub 2015 Oct 2.
- Lv MM, Zhu XY, Chen WX, Zhong SL, Hu Q, Ma TF, Zhang J, Chen L, Tang JH, Zhao JH. Exosomes mediate drug resistance transfer in MCF-7 breast cancer cells and a probable mechanism is delivery of P-glycoprotein. Tumour Biol. 2014 Nov;35(11):10773-9. doi: 10.1007/s13277-014-2377-z. Epub 2014 Jul 31.
- Kelly DL, Kreyenbuhl J, Dixon L, Love RC, Medoff D, Conley RR. Clozapine underutilization and discontinuation in African Americans due to leucopenia. Schizophr Bull. 2007 Sep;33(5):1221-4. doi: 10.1093/schbul/sbl068. Epub 2006 Dec 14.
- Xiao JF, Varghese RS, Zhou B, Nezami Ranjbar MR, Zhao Y, Tsai TH, Di Poto C, Wang J, Goerlitz D, Luo Y, Cheema AK, Sarhan N, Soliman H, Tadesse MG, Ziada DH, Ressom HW. LC-MS based serum metabolomics for identification of hepatocellular carcinoma biomarkers in Egyptian cohort. J Proteome Res. 2012 Dec 7;11(12):5914-23. doi: 10.1021/pr300673x. Epub 2012 Nov 1.
- Lynce F, Blackburn MJ, Zhuo R, Gallagher C, Hahn OM, Abu-Khalaf M, Mohebtash M, Wu T, Pohlmann PR, Dilawari A, Tiwari SR, Chitalia A, Warren R, Tan M, Shajahan-Haq AN, Isaacs C. Hematologic safety of palbociclib in combination with endocrine therapy in patients with benign ethnic neutropenia and advanced breast cancer. Cancer. 2021 Oct 1;127(19):3622-3630. doi: 10.1002/cncr.33620. Epub 2021 Jun 22.
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Actual)
1 de septiembre de 2016
Finalización primaria (Actual)
16 de diciembre de 2019
Finalización del estudio (Actual)
23 de marzo de 2021
Fechas de registro del estudio
Enviado por primera vez
23 de febrero de 2016
Primero enviado que cumplió con los criterios de control de calidad
25 de febrero de 2016
Publicado por primera vez (Estimar)
26 de febrero de 2016
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
28 de septiembre de 2021
Última actualización enviada que cumplió con los criterios de control de calidad
7 de septiembre de 2021
Última verificación
1 de agosto de 2021
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Enfermedades de la piel
- Neoplasias
- Neoplasias por sitio
- Enfermedades de los senos
- Neoplasias de mama
- Efectos fisiológicos de las drogas
- Mecanismos moleculares de acción farmacológica
- Inhibidores de enzimas
- Agentes antineoplásicos
- Hormonas, sustitutos hormonales y antagonistas hormonales
- Agentes Antineoplásicos Hormonales
- Inhibidores de la proteína quinasa
- Antagonistas de hormonas
- Inhibidores de la aromatasa
- Inhibidores de la síntesis de esteroides
- Antagonistas de estrógeno
- Antagonistas de los receptores de estrógeno
- Letrozol
- Fulvestrant
- Palbociclib
Otros números de identificación del estudio
- 2015-1396
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
NO
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .