Letrozole and Metronomic Capecitabine in ER-positive HER2 Negative Advanced Breast Cancer (B-001 Study) (B-001)

Letrozole With or Without Metronomic Capecitabine in First Line Treatment of Patients With ER-positive HER2 Negative Advanced Breast Cancer: A Randomized Phase II Study.

A phase II clinical trial designed to test the effect of combining endocrinal therapy (Letrozole) with chemotherapy (Capecitabine) in first line treatment of advanced cases of female breast cancer with ER positive disease.

Study Overview

• Status: Unknown
• Conditions: Breast Cancer; Metastatic Breast Cancer; Estrogen Receptor-positive Breast Cancer
• Intervention / Treatment: Drug: Capecitabine; Drug: Letrozole 2.5mg

Detailed Description

This is a randomized clinical trial that assigns patients with female breast cancer in the metastatic entity or advanced -beyond local disease treatment - entity into two arms. Arm A contains Letrozole with metronomic Capecitabine versus arm B that contains Letrozole alone. This is to be applied on ER positive HER2 negative tumours.

• Study Type: Interventional
• Enrollment (Anticipated): 204
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Mariam Saleh, M.D; Phone Number: +201003677227; Email: mariamsaleh309@gmail.com
• Study Contact Backup: Name: Loay Kassem, M.D; Phone Number: +201003022907; Email: loay.kassem@cairocure.com

Study Locations

• Egypt
  • Cairo, Egypt
    • Recruiting
    • Faculty of Medicine, Cairo University
    • Contact: Loay Kassem, M.D; Phone Number: +201003022907; Email: loay.kassem@cairocure.com
    • Contact: Mariam A Saleh, M.D; Phone Number: +201003677227; Email: mariamsaleh309@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Female sex
• Age 18-70
• ECOG-PS 0-II.
• Histopathological proof of breast cancer
• ER positive (Allred score of ≥3 out of 8), and HER2 negative by IHC (or ISH if HER2 +2).
• Metastatic/recurrent disease as proven by CT scan, bone scan or clinical examination (for skin lesions). Biopsy of the recurrent lesions is encouraged but not mandatory.
• Either hormone sensitive setting (Denovo metastatic disease or disease progression after more than 1 year of ending adjuvant endocrine therapy) or secondary resistance to tamoxifen therapy (disease relapse after more than 2 years of starting and less than 1 year of ending adjuvant endocrine therapy, or DP of metastatic disease after more than 6 months of first line tamoxifen).
• Adequate organ function.
• Signed informed consent

Exclusion criteria:

• Inadequate organ functions.
• Disease progression while on prior aromatase inhibitor therapy.
• Primary endocrine resistance.
• Double primary cancer (history of other malignancy apart from a non melanoma skin cancer).
• Refusal to sign consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Chemo endocrine treatment (A); Letrozole 2.5mg PO daily + Capecitabine 500mg/m2 bid PO continously	Drug: Capecitabine; Capecitabine metronomic combined with Letrozole; Other Names: Xeloda; Drug: Letrozole 2.5mg; Letrozole daily alone; Other Names: Femara
ACTIVE_COMPARATOR: Endocrine treatment only (B); Letrozole 2.5mg PO daily	Drug: Letrozole 2.5mg; Letrozole daily alone; Other Names: Femara

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6 months Progression free survival rate	Percentage of patients alive and progression-free at 6 months	6 months from the start of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate	Rate of CR+PR as assessed by the investigator using RECIST 1.1 criteria	6 months from the start of treatment
Adverse events rates in both groups	Rates of all grade (grade 1-4) and high grade (grade 3+4) adverse events as assessed by NCI-CTAE v4.0	6 months from the start of treatment
Quality of life assessment using FACIT-B questionnare	FACIT-B questionnare will be completed by each patient at baseline and 6 months after randomization	6 months
Median progression free survival	comparison of estimated median PFS between both groups	18 months
Time to treatment failure	Time from start treatment to progression, death or treatment discontinuation from any cause	18 months
Clinical benefit rate	Complete response + partial response + stable disease for 6 months	After 6 months of treatment
Overall survival	Percentage of patients alive at 24 months	24 months
Time to chemotherapy adminstration	Time from randomization to the first chemotherapy administration	18 months

Collaborators and Investigators

• Sponsor: Cairo University
• Investigators: Principal Investigator: Mariam Saleh, M.D, Cairo University

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 1, 2020
• Primary Completion (ANTICIPATED): October 31, 2021
• Study Completion (ANTICIPATED): April 30, 2022

Study Registration Dates

• First Submitted: September 25, 2020
• First Submitted That Met QC Criteria: September 25, 2020
• First Posted (ACTUAL): October 1, 2020

Study Record Updates

• Last Update Posted (ACTUAL): October 1, 2020
• Last Update Submitted That Met QC Criteria: September 25, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: metronomic capecitabine; Advanced breast cancer; chemo-hormonal; hormone positive
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Capecitabine; Letrozole
• Other Study ID Numbers: MD-127-2019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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