Maintenance Aromatase Inhibitors (AIs)+ Everolimus vs AIs in Hormone Receptor Positive Metastatic Breast Cancer Patients

Breast Cancer Metastatic Clinical Trial

— MAIN-A  

Official title:

MAINtenance Afinitor: A Randomized Trial Comparing Maintenance Aromatase Inhibitors (AIs) + Everolimus (Afinitor) vs AIs in Hormone Receptor Positive (HR+) Metastatic Breast Cancer Patients With Disease Control After First Line Chemotherapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02511639
• Other study ID #: CRAD001JIT36T
• Secondary ID: 2013-004153-24
• Status: Completed
• Phase: Phase 3
• Start date: July 30, 2014
• Est. completion date: July 31, 2020

Study information

• Verified date: December 2020
• Source: Istituto Oncologico Veneto IRCCS
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare maintenance Aromatase Inhibitors (AIs) + everolimus with Aromatase Inhibitors alone after 1st line chemotherapy in patients with HR+ metastatic breast cancer.

Description:

The purpose of this study is:

• to compare the progression free survival (PFS) of AIs/everolimus to AIs administered as maintenance therapy in HR+ advanced breast cancer patients with disease control (Complete Response (CR), Partial Response (PR) or Stable Disease (SD))after 1st line chemotherapy.

• To evaluate the overall survival

• To assess the safety profile

• To evaluate the response rate

Recruitment information / eligibility

• Status: Completed
• Enrollment: 110
• Est. completion date: July 31, 2020
• Est. primary completion date: February 28, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. >18 years old women with metastatic breast cancer

2. Histological confirmation of hormone-receptor positive (defined as at least 10% of estrogen receptor (ER) and/or progesterone receptor (PgR) positivity) and human epidermal growth factor receptor 2 (HER2) negative (score 0-1+ in immunohistochemistry or FISH negativity) breast cancer

3. Postmenopausal status

4. One line of chemotherapy for metastatic disease; patients must have received a minimum of 6 cycles of chemotherapy in order to be eligible, and must have obtained disease control (CR or PR od SD)

5. Eastern Cooperative Oncology Group (ECOG) Performance status < 2

6. Adequate bone marrow and coagulation function

7. Adequate liver function

8. Adequate renal function

9. Fasting serum cholesterol = 300 mg/dl or 7.75 mmol/L and fasting triglycerides = 2.5 × upper limit of normal (ULN). In case one or both of these thresholds are exceeded, the patient can only be included after initiation of statin therapy or other lipid lowering drugs (eg fibrates), and when the above mentioned values have been achieved

10. Fasting glucose < 1.5 × ULN

11. Written informed consent obtained before any screening procedure and according to local guidelines.

Exclusion Criteria:

1. HER2-overexpressing patients by local laboratory testing (immunohistochemistry 3+ staining or in situ hybridization positive)

2. Previous treatment with mammalian target of rapamycin (mTOR) inhibitors

3. Known hypersensitivity to mTOR inhibitors, e.g. sirolimus (rapamycin)

4. More than one chemotherapy line for metastatic disease

5. Treatment with angiogenetic compounds as maintenance therapy (eg. bevacizumab)

6. Radiotherapy within four weeks prior to enrollment except in case of localized radiotherapy for analgesic purpose or for lytic lesions at risk of fracture which can then be completed within two weeks prior to enrollment. Patients must have recovered from radiotherapy toxicities prior to enrollment

7. Symptomatic central nervous system metastases

8. Patients with a known history of HIV positivity

9. Active, bleeding diathesis, or on oral anti-vitamin K medication (except low dose warfarin and acetylsalicylic acid or equivalent, as long as the international normalized ratio (INR) is = 2.0)

10. Any severe and / or uncontrolled medical conditions such as:

• Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction =6 months prior to enrollment, serious uncontrolled cardiac arrhythmia

• Uncontrolled diabetes as defined by fasting serum glucose > 1.5 × ULN

• Acute and chronic, active infectious disorders and nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this study therapy

• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of study drugs (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome)

• Significant symptomatic deterioration of lung function. If clinically indicated, pulmonary function tests including measures of predicted lung volumes, diffusion capacity of lung for carbon monoxide (DLco) and O2 saturation at rest on room air should be considered to exclude restrictive pulmonary disease, pneumonitis or pulmonary infiltrates.

11. Patients who test positive for hepatitis B or C (patients who test negative for hepatitis B virus (HBV)-DNA, HBsAg, and HBcAb but positive for HBsAb with prior history of vaccination against Hepatitis B will be eligible)

12. Patients being treated with drugs recognized as being strong inhibitors or inducers of the isoenzyme Cytochrome P3A (Rifabutin, Rifampicin, Clarithromycin, Ketoconazole, Itraconazole, Voriconazole, Ritonavir, Telithromycin) within the last 5 days prior to enrollment

13. History of non-compliance to medical regimens

14. Patients unwilling to or unable to comply with the protocol

Related Conditions & MeSH terms

• Breast Cancer Metastatic
• Breast Neoplasms

Intervention

Drug:
• Everolimus
Everolimus is formulated as tablets of 10 mg strength for oral administration.
• Aromatase Inhibitors
Anastrozole is formulated as tablets of 1 mg strength for oral administration. Letrozole is formulated as tablets of 2.5 mg strength for oral administration. Exemestane is formulated as tablets of 25 mg strength for oral administration.

Locations

Country	Name	City	State
Italy	Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona	Ancona	AN
Italy	Ospedale Papa Giovanni XXIII	Bergamo	Bg
Italy	Policlinico Sant'Orsola Malpighi	Bologna	BO
Italy	Azienda Spedali Civili di Brescia	Brescia	BS
Italy	ASL Brindisi "Antonio Perrini"	Brindisi	BR
Italy	Azienda Ospedaliero - Universitaria "Policlinico - Vittorio Emanuele"	Catania	CT
Italy	Azienda Ospedaliero-Universitaria di Ferrara - Arcispedale Sant'Anna	Cona	FE
Italy	A.S.O. S.Croce e Carle di Cuneo	Cuneo	CN
Italy	Ospedale Misericordia di Grosseto	Grosseto	GR
Italy	Ospedale dell'Angelo	Mestre
Italy	Istituto Nazionale dei Tumori IRCCS	Milano	MI
Italy	Ospedale Sacro Cuore - Don Calabria	Negrar	VR
Italy	Azienda Ospedaliera Universitaria di Parma	Parma	PR
Italy	IRCCS - Azienda Ospedaliera S.M. Nuova	Reggio Emilia	RE
Italy	Ospedale Civile Santa Chiara	Trento	TN
Italy	Azienda Ospedaliero-Universitaria "Santa Maria della Misericordia"	Udine	UD

Sponsors (2)

Lead Sponsor	Collaborator
Istituto Oncologico Veneto IRCCS	University of Padova

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival	PFS is defined as the time from randomization to the first documentation of objective disease progression or death from any cause	Up to 2 years after randomisation
Secondary	Overall survival	Overall survival is defined as the interval between the date of randomization and the date of patient death due to any cause, or the last date the patient was known to be alive	Up to 2 years after randomisation
Secondary	Response rate	Responses will be assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria only for patients with measurable disease at the time of study entry.	Every 12 weeks during treatment, up to 2 years after randomisation
Secondary	Safety profile	Toxicity will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI -CTCAE), version 4.	Baseline and every 4 weeks during treatment, up to 2 years after randomisation