Letrozole Plus Metronomic Capecitabine as First-line Treatment for Patients With Recurrent or Metastatic Breast Cancer
Primary Purpose
Metastasis Breast
Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
letrozole
Sponsored by
About this trial
This is an interventional prevention trial for Metastasis Breast focused on measuring breast cancer
Eligibility Criteria
Inclusion Criteria:
- Confirmed diagnosis of hormonal receptor-positive (HR+)/Her2-negative breast cancer
- No prior systemic anti-cancer therapy for advanced HR+ disease except tamoxifen treatment in adjuvant sitting
- If the patient is pre-/peri- menopausal, a luteinizing hormone-releasing hormone (LHRH) agonist will be given for at least 28 days before randomization or ovarian ablation or suppression by surgery or radiotherapy
- Measurable disease defined by RECIST version 1.1,
- Eastern Cooperative Oncology Group (ECOG) 0-1
- Adequate organ and marrow function.
Exclusion Criteria:
- Patients with advanced, symptomatic visceral spread (visceral crisis)
- Patients diagnosed with central nervous system metastases
- Second primary malignancy
Sites / Locations
Outcomes
Primary Outcome Measures
tumor response
tumor response in form of change tumor size
Secondary Outcome Measures
progression free survival
decrease sites of metastasis
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04942899
Brief Title
Letrozole Plus Metronomic Capecitabine as First-line Treatment for Patients With Recurrent or Metastatic Breast Cancer
Official Title
Aromatase Inhibitors Plus Metronomic Capecitabine in Treatment of Patients With Recurrent or Metastatic Hormone Receptor Positive, HER2 Negative Breast Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
August 30, 2023 (Anticipated)
Primary Completion Date
August 1, 2024 (Anticipated)
Study Completion Date
May 31, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Assiut University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
5. Study Description
Brief Summary
The study is designed to assess the treatment outcomes following treatment with letrozole plus metronomic capecitabine in patients with hormone receptor-positive, Her2-negative advanced breast cancer who have not received prior systemic anti-cancer therapies for their recurrent /metastatic disease.
Detailed Description
Breast cancer is recognized as the commonest cancer in females, and the second commonest malignant tumor, after lung cancer, in overall figures worldwide.
In 2021, an estimated 281,550 new cases of invasive breast cancer are expected to be diagnosed in women in the U.S., along with 49,290 new cases of non-invasive (in situ) breast cancer.
About 43,600 women in the U.S. are expected to die in 2021 from breast cancer. Death rates have been steady in women under 50 since 2007, but have continued to drop in women over 50. The overall death rate from breast cancer decreased by 1% per year from 2013 to 2018. These decreases are thought to be the result of treatment advances and earlier detection through screening.
According to the World Health Organization, breast cancer became the most common cancer globally as of 2021, accounting for 12% of all new annual cancer cases worldwide.
Breast cancer is increasingly recognized as a heterogeneous disease exhibiting substantial differences concerning biological behavior and requiring distinct therapeutic interventions. There has been a continuous decline in mortality over recent years due to improvements in early diagnosis and the increased availability of more effective treatments. However, despite these improvements, The treatment of hormone receptor-positive metastatic breast cancer (MBC) who developed disease progression on first-line hormonal treatment that included aromatase inhibitors (AI) represents a challenge as those patients ultimately develop resistant disease unresponsive to standard lines of estrogen receptors (ER) blockade. Capecitabine is an oral chemotherapy that mimics continuous infusion of 5-FU with known activity in MBC. It might be preferred because of its tolerability and relatively lower toxicity than other chemotherapeutic agents. Metronomic chemotherapy is defined as the frequent (daily, many times a week, or weekly) or continuous administration of low dose chemotherapeutic agents, without prolonged drug-free intervals. This way of administration improves the antiangiogenic activity of chemotherapy. Another important advantage of this approach is the significant reduction in toxicity. Capecitabine's pharmacokinetics and high safety profile make it a suitable drug for metronomic administration. Many studies reported that the overall response rate can be improved by (15.8-21.7%) when metronomic chemotherapy is combined with aromatase inhibitors. This combination can also decrease the level of both the Ki-67 index and VEGF-A significantly in the tumor tissue. It was reported that the patients who received letrozole plus metronomic chemotherapy achieved a higher overall response rate (ORR) than those who received letrozole alone (87.7% vs 71.9% respectively.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastasis Breast
Keywords
breast cancer
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
70 (Anticipated)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
letrozole
Other Intervention Name(s)
capecitabine
Intervention Description
concurrent capecitabine 500 mg three times daily in combination with letrozole 2.5 mg orally once daily.
Primary Outcome Measure Information:
Title
tumor response
Description
tumor response in form of change tumor size
Time Frame
1 year
Secondary Outcome Measure Information:
Title
progression free survival
Description
decrease sites of metastasis
Time Frame
1 year
10. Eligibility
Sex
Female
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Female patients > 18 years old with loco regionally recurrent or metastatic disease not amenable to curative therapy
Confirmed diagnosis of hormonal receptor positive (HR+)/Her2-negative breast cancer
If the patient is pre-/peri- menopausal, a luteinizing hormone releasing hormone (LHRH) agonist will be given for at least 28 days before randomization or ovarian ablation or suppression by surgery or radiotherapy
Measurable disease defined by RECIST version 1.1,
Eastern Cooperative Oncology Group (ECOG) 0-2
Adequate organ and marrow function
Exclusion Criteria:
Patients with advanced, symptomatic visceral spread (visceral crisis)
Patients diagnosed with central nervous system metastases
Second primary malignancy
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yosra Farghaly Sayed, Assistant Lecturer
Phone
+201110260531
Email
yousrafarghaly@aun.edu.eg
First Name & Middle Initial & Last Name or Official Title & Degree
Hanan Gamal El-din Mostafa, professor doctor
Phone
+201004082002
Email
mostafahanan36@yahoo.com
12. IPD Sharing Statement
Citations:
PubMed Identifier
25735384
Citation
Shankar A, Rath G, Roy S, Malik A, Bhandari R, Kishor K, Barnwal K, Upadyaya S, Srivastava V, Singh R. Level of awareness of cervical and breast cancer risk factors and safe practices among college teachers of different states in india: do awareness programmes have an impact on adoption of safe practices? Asian Pac J Cancer Prev. 2015;16(3):927-32. doi: 10.7314/apjcp.2015.16.3.927.
Results Reference
background
PubMed Identifier
15894097
Citation
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.
Results Reference
background
PubMed Identifier
19711579
Citation
Winkfield KM, Harris JR. Effective local therapy and long-term survival in breast cancer. Oncology (Williston Park). 2009 Jul;23(8):669-75.
Results Reference
background
PubMed Identifier
24268206
Citation
Schwartzberg LS, Wang G, Somer BG, Blakely LJ, Wheeler BM, Walker MS, Stepanski EJ, Houts AC. Phase II trial of fulvestrant with metronomic capecitabine for postmenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer. Clin Breast Cancer. 2014 Feb;14(1):13-9. doi: 10.1016/j.clbc.2013.09.003. Epub 2013 Sep 27.
Results Reference
background
PubMed Identifier
11689577
Citation
Van Cutsem E, Twelves C, Cassidy J, Allman D, Bajetta E, Boyer M, Bugat R, Findlay M, Frings S, Jahn M, McKendrick J, Osterwalder B, Perez-Manga G, Rosso R, Rougier P, Schmiegel WH, Seitz JF, Thompson P, Vieitez JM, Weitzel C, Harper P; Xeloda Colorectal Cancer Study Group. Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. J Clin Oncol. 2001 Nov 1;19(21):4097-106. doi: 10.1200/JCO.2001.19.21.4097.
Results Reference
background
PubMed Identifier
12454316
Citation
Seidman AD, O'Shaughnessy J, Misset JL. Single-agent capecitabine: a reference treatment for taxane-pretreated metastatic breast cancer? Oncologist. 2002;7 Suppl 6:20-8. doi: 10.1634/theoncologist.7-suppl_6-20.
Results Reference
background
PubMed Identifier
15763604
Citation
Walko CM, Lindley C. Capecitabine: a review. Clin Ther. 2005 Jan;27(1):23-44. doi: 10.1016/j.clinthera.2005.01.005.
Results Reference
background
PubMed Identifier
19884008
Citation
Munzone E, Di Pietro A, Goldhirsch A, Minchella I, Verri E, Cossu Rocca M, Marenghi C, Curigliano G, Radice D, Adamoli L, Nole F. Metronomic administration of pegylated liposomal-doxorubicin in extensively pre-treated metastatic breast cancer patients: a mono-institutional case-series report. Breast. 2010 Feb;19(1):33-7. doi: 10.1016/j.breast.2009.10.003. Epub 2009 Nov 1.
Results Reference
background
PubMed Identifier
18591566
Citation
Mehta RS. Dose-dense and/or metronomic schedules of specific chemotherapies consolidate the chemosensitivity of triple-negative breast cancer: a step toward reversing triple-negative paradox. J Clin Oncol. 2008 Jul 1;26(19):3286-8; author reply 3288. doi: 10.1200/JCO.2008.17.1116. No abstract available.
Results Reference
background
PubMed Identifier
18063872
Citation
Emmenegger U, Kerbel RS. Five years of clinical experience with metronomic chemotherapy: achievements and perspectives. Onkologie. 2007 Dec;30(12):606-8. doi: 10.1159/000111479. Epub 2007 Nov 30. No abstract available.
Results Reference
background
PubMed Identifier
16877730
Citation
Bottini A, Generali D, Brizzi MP, Fox SB, Bersiga A, Bonardi S, Allevi G, Aguggini S, Bodini G, Milani M, Dionisio R, Bernardi C, Montruccoli A, Bruzzi P, Harris AL, Dogliotti L, Berruti A. Randomized phase II trial of letrozole and letrozole plus low-dose metronomic oral cyclophosphamide as primary systemic treatment in elderly breast cancer patients. J Clin Oncol. 2006 Aug 1;24(22):3623-8. doi: 10.1200/JCO.2005.04.5773.
Results Reference
background
PubMed Identifier
10655437
Citation
Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000 Feb 2;92(3):205-16. doi: 10.1093/jnci/92.3.205.
Results Reference
background
Learn more about this trial
Letrozole Plus Metronomic Capecitabine as First-line Treatment for Patients With Recurrent or Metastatic Breast Cancer
We'll reach out to this number within 24 hrs