Palbociclib / Letrozole or Fulvestrant in African American Women With HR+ HER2- Breast Cancer

NCT02692755 | Completed Phase 2 Results DMC

• 1 other identifier: 2015-1396
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 6

Brief Summary

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

Conditions

Hormone Receptor Positive HER-2 Negative Breast Cancer

Keywords

African American

Outcome Measures

Primary Outcomes (1)

• Number of Patients Who Complete Planned Oncologic Therapy Without the Development of a Hematological Event

  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

Secondary Outcomes (3)

• Dose Delays in Palbociclib Attributed to Neutropenia

  12 months

• Dose Reductions in Palbociclib Therapy Attributed to Neutropenia

  12 months

• Clinical Benefit Rate

  24 weeks

Study Arms (1)

Palbociclib + Letrozole or Fulvestrant

EXPERIMENTAL

Drug: Palbociclib + Letrozole or Fulvestrant

Interventions

Palbociclib + Letrozole or Fulvestrant DRUG

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

Also known as: Ibrance, Femara, Faslodex

Palbociclib + Letrozole or Fulvestrant

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Georgetown University: lead
• University of Chicago: collaborator
• Thomas Jefferson University: collaborator

Study Sites (6)

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

MedStar Washington Hospital Center

Washington D.C., District of Columbia, 20013, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

MedStar Union Memorial Hospital

Baltimore, Maryland, 21218, United States

Location

MedStar Good Samaritan Hospital

Baltimore, Maryland, 21239, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Related Publications (31)

• Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010 Sep-Oct;60(5):277-300. doi: 10.3322/caac.20073. Epub 2010 Jul 7.

  PMID: 20610543 BACKGROUND

• Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005 May 14-20;365(9472):1687-717. doi: 10.1016/S0140-6736(05)66544-0.

  PMID: 15894097 BACKGROUND

• 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.

  BACKGROUND

• 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.

  PMID: 3611201 BACKGROUND

• 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.

  PMID: 6871841 BACKGROUND

• 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.

  PMID: 12775735 BACKGROUND

• 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.

  PMID: 19874578 BACKGROUND

• 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.

  PMID: 21610706 BACKGROUND

• 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.

  PMID: 22090362 BACKGROUND

• 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.

  PMID: 25501126 BACKGROUND

• 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.

  PMID: 25524798 BACKGROUND

• 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

  BACKGROUND

• 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.

  PMID: 26488700 BACKGROUND

• NIH Policy and Guidelines on The Inclusion of Women and Minorities as Subjects in Clinical Research - Amended, October, 2001

  BACKGROUND

• 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.

  PMID: 24643646 BACKGROUND

• 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.

  PMID: 17404350 BACKGROUND

• 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.

  PMID: 19180233 BACKGROUND

• 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.

  PMID: 20194862 BACKGROUND

• 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.

  PMID: 14559877 BACKGROUND

• 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.

  PMID: 25693144 BACKGROUND

• Nowicki S, Gottlieb E. Oncometabolites: tailoring our genes. FEBS J. 2015 Aug;282(15):2796-805. doi: 10.1111/febs.13295. Epub 2015 Apr 30.

  PMID: 25864878 BACKGROUND

• Gunther UL. Metabolomics Biomarkers for Breast Cancer. Pathobiology. 2015 Sep;82(3-4):153-65. doi: 10.1159/000430844. Epub 2015 Aug 31.

  PMID: 26330356 BACKGROUND

• Shajahan-Haq AN, Cook KL, Schwartz-Roberts JL, Eltayeb AE, Demas DM, Warri AM, Facey CO, Hilakivi-Clarke LA, Clarke R. MYC regulates the unfolded protein response and glucose and glutamine uptake in endocrine resistant breast cancer. Mol Cancer. 2014 Oct 23;13:239. doi: 10.1186/1476-4598-13-239.

  PMID: 25339305 BACKGROUND

• 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.

  PMID: 20959483 BACKGROUND

• Lowry MC, Gallagher WM, O'Driscoll L. The Role of Exosomes in Breast Cancer. Clin Chem. 2015 Dec;61(12):1457-65. doi: 10.1373/clinchem.2015.240028. Epub 2015 Oct 14.

  PMID: 26467503 BACKGROUND

• Yu S, Cao H, Shen B, Feng J. Tumor-derived exosomes in cancer progression and treatment failure. Oncotarget. 2015 Nov 10;6(35):37151-68. doi: 10.18632/oncotarget.6022.

  PMID: 26452221 BACKGROUND

• 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.

  PMID: 26432333 BACKGROUND

• 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.

  PMID: 25077924 BACKGROUND

• 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.

  PMID: 17170061 BACKGROUND

• 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.

  PMID: 23078175 BACKGROUND

• 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.

  PMID: 34157782 DERIVED

MeSH Terms

Interventions

palbociclib; Letrozole; Fulvestrant

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Nicole Swanson
• Organization: Georgetown University

ns1209@georgetown.edu

2026879194

Study Officials

• Claudine Isaacs, MD

  MedStar Georgetown University Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2016
• First Posted: February 26, 2016
• Study Start: September 1, 2016
• Primary Completion: December 16, 2019
• Study Completion: March 23, 2021
• Last Updated: September 28, 2021
• Results First Posted: August 20, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)