Tamoxifen-RAD001 Versus Tamoxifen Alone in Patients With Anti-aromatase Resistant Breast Metastatic Cancer
Primary Purpose
Breast Neoplasms, mTor Protein
Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Tamoxifen
Everolimus
Sponsored by
About this trial
This is an interventional treatment trial for Breast Neoplasms focused on measuring Hormonoresistance, tamoxifen, Previously received anti-aromatase treatment, mTor inhibitor
Eligibility Criteria
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
Sites / Locations
- Hopital Hotel Dieu
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
A
B
Arm Description
Tamoxifen 20mg/d
Tamoxifen 20mg/d + RAD001 10mg/d
Outcomes
Primary Outcome Measures
Clinical benefit at 24 weeks
Secondary Outcome Measures
Partial and complete response per RECIST
Qualitative and quantitative toxicities
Overall survival
Full Information
NCT ID
NCT01298713
First Posted
February 16, 2011
Last Updated
September 5, 2023
Sponsor
ARCAGY/ GINECO GROUP
Collaborators
Novartis
1. Study Identification
Unique Protocol Identification Number
NCT01298713
Brief Title
Tamoxifen-RAD001 Versus Tamoxifen Alone in Patients With Anti-aromatase Resistant Breast Metastatic Cancer
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
March 2008 (Actual)
Primary Completion Date
June 2011 (Actual)
Study Completion Date
September 12, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ARCAGY/ GINECO GROUP
Collaborators
Novartis
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Neoplasms, mTor Protein
Keywords
Hormonoresistance, tamoxifen, Previously received anti-aromatase treatment, mTor inhibitor
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
111 (Actual)
8. Arms, Groups, and Interventions
Arm Title
A
Arm Type
Active Comparator
Arm Description
Tamoxifen 20mg/d
Arm Title
B
Arm Type
Experimental
Arm Description
Tamoxifen 20mg/d + RAD001 10mg/d
Intervention Type
Drug
Intervention Name(s)
Tamoxifen
Intervention Description
20mg daily (1 cap) until unbearable toxicity or progression
Intervention Type
Drug
Intervention Name(s)
Everolimus
Other Intervention Name(s)
RAD001
Intervention Description
10mg daily (2 caps of 5mg) until unbearable toxicity or progression
Primary Outcome Measure Information:
Title
Clinical benefit at 24 weeks
Time Frame
42 months
Secondary Outcome Measure Information:
Title
Partial and complete response per RECIST
Time Frame
42 months
Title
Qualitative and quantitative toxicities
Time Frame
24 months
Title
Overall survival
Time Frame
42 months
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Hopital Hotel Dieu
City
Paris
ZIP/Postal Code
75004
Country
France
12. IPD Sharing Statement
Citations:
PubMed Identifier
25361980
Citation
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.
Results Reference
derived
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Tamoxifen-RAD001 Versus Tamoxifen Alone in Patients With Anti-aromatase Resistant Breast Metastatic Cancer
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