Tamoxifen-RAD001 Versus Tamoxifen Alone in Patients With Anti-aromatase Resistant Breast Metastatic Cancer

Phase 2 Study Assessing the Tolerance and Efficacy of Tamoxifen Alone Versus the Association Tamoxifen-RAD001 (Everolimus) in Patients With Anti-aromatase Resistant Breast Metastatic Cancer

Tamoxifen is a classical treatment for breast metastatic cancer after 3rd generation anti-aromatase hormonotherapy in adjuvant or in metastatic line. The Tamoxifen efficacy is lowered by the hormonoresistance mechanisms due to the primary use of the anti-aromatases. The Pi3K-AKT-mTor pathway is frequently associated to the hormonoresistance mechanisms. This study is aimed to check if the inhibition of this signal transduction pathway by a synthetic mTor inhibitor (Everolimus) could improve the efficacy of the Tamoxifen.

Study Overview

• Status: Completed
• Conditions: Breast Neoplasms; mTor Protein
• Intervention / Treatment: Drug: Tamoxifen; Drug: Everolimus

• Study Type: Interventional
• Enrollment (Actual): 111
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Paris, France, 75004
    • Hôpital Hotel Dieu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Menopausal female patient aged > 18 years
• Histologically proven breast adenocarcinoma
• ER and/or PR positive receptors and HER2 negative
• previously received first or second line of hormonotherapy for metastatic disease
• previously treated with anti-aromatase in adjuvant and/or in metastatic line
• presence of one or several mesurable or evaluable metastatic lesion(s)
• presence of at least one target lesion not previously irradiated
• ECOG Performance status < 2
• adequate biological values
• patient who has clearly given her consent by signing on informed consent form prior to participation

Exclusion Criteria:

• patient with only local metastatic disease that can be treted by surgery
• uncotrolled brain metastases, pulmonary carcinomatosal lymphangitis, hepatic metastases
• Previous treatment by Tamoxifen unless in adjuvant and terminated more than a year before metastatic relapse
• Patient with a tumor surexpressing HER2 that should be treated by trastuzumab
• Patient that need an immediate local antalgic radiotherapy
• Thrombo-embolism disease
• serious concomitant pathology or uncontrolled that is susceptible to compromise the participation in the study
• history of another malignancy within past 5 years that could confound diagnosis or staging of breast cancer (with the exception of in situ cacinoma of the cervix or adequately treated basel cell carcinoma of the skin) and cancers cured for at least for 5 years
• patient with an history of significant cardiovascular impairment (congestive heart failure> NYHA grade II, unstable angina or myocardial infraction within the past six months or serious cardiac arrhythmia)
• patient with any medical or psychiatric condition that, in the opinion of the Principal Investigator, would preclude her from participating in this study
• patient with a known allergy to one or several of the study compounds
• patients who may not be regularly available due to geographical, social or family reasons
• history of renal, hepatic or metabolic pathology that could preclude with metabolism or elimination of the study product
• deficiencies of the upper intestinal tract, malabsorption syndrome
• patient who is pregnant, breast-feeding or using inadequate contraception
• Treatment with experimental drugs (mTor inhibitor or tyrosin kinase inhibitor)
• Patient treated with molecules that interfer with isoenzyme CYP3A

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: A; Tamoxifen 20mg/d	Drug: Tamoxifen; 20mg daily (1 cap) until unbearable toxicity or progression
Experimental: B; Tamoxifen 20mg/d + RAD001 10mg/d	Drug: Tamoxifen; 20mg daily (1 cap) until unbearable toxicity or progression; Drug: Everolimus; 10mg daily (2 caps of 5mg) until unbearable toxicity or progression; Other Names: RAD001

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Clinical benefit at 24 weeks	42 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Partial and complete response per RECIST	42 months
Qualitative and quantitative toxicities	24 months
Overall survival	42 months

Collaborators and Investigators

• Sponsor: ARCAGY/ GINECO GROUP
• Collaborators: Novartis
• Investigators: Principal Investigator: Thomas Bachelot, MD, ARCAGY-GINECO

Publications and helpful links

General Publications

• Treilleux I, Arnedos M, Cropet C, Wang Q, Ferrero JM, Abadie-Lacourtoisie S, Levy C, Legouffe E, Lortholary A, Pujade-Lauraine E, Bourcier AV, Eymard JC, Spaeth D, Bachelot T. Translational studies within the TAMRAD randomized GINECO trial: evidence for mTORC1 activation marker as a predictive factor for everolimus efficacy in advanced breast cancer. Ann Oncol. 2015 Jan;26(1):120-125. doi: 10.1093/annonc/mdu497. Epub 2014 Oct 31.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2008
• Primary Completion (Actual): June 1, 2011
• Study Completion (Actual): September 12, 2018

Study Registration Dates

• First Submitted: February 16, 2011
• First Submitted That Met QC Criteria: February 16, 2011
• First Posted (Estimated): February 18, 2011

Study Record Updates

• Last Update Posted (Actual): September 6, 2023
• Last Update Submitted That Met QC Criteria: September 5, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: tamoxifen; mTor inhibitor; Hormonoresistance; Previously received anti-aromatase treatment
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Neoplastic Processes; Breast Neoplasms; Neoplasm Metastasis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protein Kinase Inhibitors; Hormone Antagonists; Bone Density Conservation Agents; Estrogen Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; MTOR Inhibitors; Tamoxifen; Everolimus
• Other Study ID Numbers: TAMRAD; EUDRACT 2006-004332-79