Trial Outcomes & Findings for Exemestane-RAD001-Metformin (NCT NCT01627067)

NCT ID: NCT01627067

Last Updated: 2020-06-19

Results Overview

The primary end point of this study was progression-free survival (PFS), defined as the time from study enrollment to disease progression or death from any cause, whichever occurred first. Data for PFS were censored at the time of a patient's removal from study. All other analyses were post-hoc and should be regarded as such.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 23 participants
• Primary outcome timeframe: From the registration until disease progression, death, unacceptable toxicity, or withdraw of study consent, whichever occurred first assessed up to 67 months
• Results posted on: 2020-06-19

Participant Flow

Patients were recruited from October 2012 to September 2013. The participating subjects must sign the consent document pertaining to the study and meet all the eligibility criteria as mentioned in the protocol, before initiating on the study treatment.

Participant milestones

Measure	Everolimus + Exemestane + Metformin Exemestane 25 mg by mouth once a day daily for 28, Everolimus 10 mg by mouth once a day daily for 28, days and Metformin upto 1000 mg by mouth twice a day daily for 28 days cycle.
Overall Study STARTED	23
Overall Study COMPLETED	22
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure	Everolimus + Exemestane + Metformin Exemestane 25 mg by mouth once a day daily for 28, Everolimus 10 mg by mouth once a day daily for 28, days and Metformin upto 1000 mg by mouth twice a day daily for 28 days cycle.
Overall Study Screen Failure	1

Baseline Characteristics

Exemestane-RAD001-Metformin

Baseline characteristics by cohort

Measure	Everolimus + Exemestane + Metformin n=22 Participants Exemestane 25 mg by mouth once a day daily for 28, Everolimus 10 mg by mouth once a day daily for 28, days and Metformin upto 1000 mg by mouth twice a day daily for 28 days cycle.
Age, Continuous	57.2 years n=5 Participants
Sex: Female, Male Female	22 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants
Race (NIH/OMB) White	20 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	22 participants n=5 Participants

PRIMARY outcome

Timeframe: From the registration until disease progression, death, unacceptable toxicity, or withdraw of study consent, whichever occurred first assessed up to 67 months

The primary end point of this study was progression-free survival (PFS), defined as the time from study enrollment to disease progression or death from any cause, whichever occurred first. Data for PFS were censored at the time of a patient's removal from study. All other analyses were post-hoc and should be regarded as such.

Outcome measures

Measure	Everolimus + Exemestane + Metformin n=22 Participants Exemestane 25 mg by mouth once a day daily for 28, Everolimus 10 mg by mouth once a day daily for 28, days and Metformin upto 1000 mg by mouth twice a day daily for 28 days cycle.
Progression-Free Survival (PFS)	6.3 months Interval 3.8 to 11.3

PRIMARY outcome

Timeframe: From the registration until disease progression, death, unacceptable toxicity, or withdraw of study consent, whichever occurred first assessed up to 67 months

The primary end point of this study was progression-free survival (PFS), defined as the time from study enrollment to disease progression or death from any cause, whichever occurred first. Data for PFS were censored at the time of a participants removal from study. Compare PFS between overweight patients (n=11; BMI </=25 kg/m2) and obese patient ( n=11; BMI >/=25 kg/m2) on univariable cox regression analysis.

Outcome measures

Measure	Everolimus + Exemestane + Metformin n=22 Participants Exemestane 25 mg by mouth once a day daily for 28, Everolimus 10 mg by mouth once a day daily for 28, days and Metformin upto 1000 mg by mouth twice a day daily for 28 days cycle.
Compare Progression Free Survival (PFS) Between the Number of Obese and Overweight Participants Obese participants	11 Participants
Compare Progression Free Survival (PFS) Between the Number of Obese and Overweight Participants Overweight participants	11 Participants

POST_HOC outcome

Timeframe: From the registration until disease progression, death, unacceptable toxicity, or withdraw of study consent, whichever occurred first assessed up to 67 months

Overall survival (OS) was defined as the time from study enrollment to death from any cause. Data on vital status were collected after study completion through May 1, 2018 and were used in the determination of OS.

Outcome measures

Measure	Everolimus + Exemestane + Metformin n=22 Participants Exemestane 25 mg by mouth once a day daily for 28, Everolimus 10 mg by mouth once a day daily for 28, days and Metformin upto 1000 mg by mouth twice a day daily for 28 days cycle.
Overall Survival (OS)	28.8 months Interval 17.5 to 59.7

POST_HOC outcome

Timeframe: From the registration until disease progression, death, unacceptable toxicity, or withdraw of study consent, whichever occurred first assessed up to 67 months

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. The clinical benefit rate (CBR) was defined as the proportion of patients with a best overall response of CR, PR or SD (non-CR/non-PD for patients without measurable disease) lasting at least 24 weeks. For patients with a best overall response of CR or PR, the duration of response (DOR) was defined as the time from first documentation of CR or PR to the time of disease progression. Data on the DOR and PFS were censored at the time of a patient's removal from the study. For patients with a best overall response of SD (non-CR/non-PD for patients without measurable disease),the duration of SD (non-CR/non-PD for patients without measurable disease) was defined as the time from study enrollment to the time of disease progression.

Outcome measures

Measure	Everolimus + Exemestane + Metformin n=22 Participants Exemestane 25 mg by mouth once a day daily for 28, Everolimus 10 mg by mouth once a day daily for 28, days and Metformin upto 1000 mg by mouth twice a day daily for 28 days cycle.
Number of Participants With Response Complete Response	0 Participants
Number of Participants With Response Partial response	5 Participants
Number of Participants With Response Stable Disease lasting >=24 wks	7 Participants
Number of Participants With Response Stable Disease lasting <24 wks	5 Participants
Number of Participants With Response Progressive disease	5 Participants
Number of Participants With Response Overall response (CR+PR)	5 Participants
Number of Participants With Response Clinical benefit (CR+PR+SD >/= 24 wks	12 Participants

POST_HOC outcome

Timeframe: From the registration until disease progression, death, unacceptable toxicity, or withdraw of study consent, whichever occurred first assessed up to 67 months

Overall survival (OS) was defined as the time from study enrollment to death from any cause. Data on vital status were collected after study completion through May 1, 2018 and were used in the determination of OS. Compare OS between obese participants ( n=11; BMI >/=25 kg/m2) and overweight participants (n=11; BMI </=25 kg/m2) on univariable cox regression analysis.

Outcome measures

Measure	Everolimus + Exemestane + Metformin n=22 Participants Exemestane 25 mg by mouth once a day daily for 28, Everolimus 10 mg by mouth once a day daily for 28, days and Metformin upto 1000 mg by mouth twice a day daily for 28 days cycle.
Compare Overall Survival (OS) Between the Number of Obese and Overweight Participants Obese participants	11 Participants
Compare Overall Survival (OS) Between the Number of Obese and Overweight Participants Overweight participants	11 Participants

Adverse Events

Everolimus + Exemestane + Metformin

Serious events: 1 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Measure	Everolimus + Exemestane + Metformin n=22 participants at risk Exemestane 25 mg by mouth once a day daily for 28, Everolimus 10 mg by mouth once a day daily for 28, days and Metformin upto 1000 mg by mouth twice a day daily for 28 days cycle.
Gastrointestinal disorders Nausea	4.5% 1/22 • Adverse events collected from the initiation of study drugs until disease progression, death, unacceptable toxicity, or withdraw of study consent, whichever occurred first assessed up to 67 months There were no deaths. All participants survived.
Gastrointestinal disorders Vomitting	4.5% 1/22 • Adverse events collected from the initiation of study drugs until disease progression, death, unacceptable toxicity, or withdraw of study consent, whichever occurred first assessed up to 67 months There were no deaths. All participants survived.
Renal and urinary disorders Acute kidney injury	4.5% 1/22 • Adverse events collected from the initiation of study drugs until disease progression, death, unacceptable toxicity, or withdraw of study consent, whichever occurred first assessed up to 67 months There were no deaths. All participants survived.

Other adverse events

Measure	Everolimus + Exemestane + Metformin n=22 participants at risk Exemestane 25 mg by mouth once a day daily for 28, Everolimus 10 mg by mouth once a day daily for 28, days and Metformin upto 1000 mg by mouth twice a day daily for 28 days cycle.
Gastrointestinal disorders Nausea (grade 2)	13.6% 3/22 • Number of events 3 • Adverse events collected from the initiation of study drugs until disease progression, death, unacceptable toxicity, or withdraw of study consent, whichever occurred first assessed up to 67 months There were no deaths. All participants survived.
Gastrointestinal disorders Vomitting (grade 2)	13.6% 3/22 • Number of events 3 • Adverse events collected from the initiation of study drugs until disease progression, death, unacceptable toxicity, or withdraw of study consent, whichever occurred first assessed up to 67 months There were no deaths. All participants survived.
Gastrointestinal disorders Diarrhea (grade 2)	13.6% 3/22 • Number of events 3 • Adverse events collected from the initiation of study drugs until disease progression, death, unacceptable toxicity, or withdraw of study consent, whichever occurred first assessed up to 67 months There were no deaths. All participants survived.
Investigations Fatigue	27.3% 6/22 • Number of events 6 • Adverse events collected from the initiation of study drugs until disease progression, death, unacceptable toxicity, or withdraw of study consent, whichever occurred first assessed up to 67 months There were no deaths. All participants survived.
Metabolism and nutrition disorders Weight loss	59.1% 13/22 • Number of events 13 • Adverse events collected from the initiation of study drugs until disease progression, death, unacceptable toxicity, or withdraw of study consent, whichever occurred first assessed up to 67 months There were no deaths. All participants survived.
Gastrointestinal disorders Mucositis	45.5% 10/22 • Number of events 10 • Adverse events collected from the initiation of study drugs until disease progression, death, unacceptable toxicity, or withdraw of study consent, whichever occurred first assessed up to 67 months There were no deaths. All participants survived.
Hepatobiliary disorders AST elevation	22.7% 5/22 • Number of events 5 • Adverse events collected from the initiation of study drugs until disease progression, death, unacceptable toxicity, or withdraw of study consent, whichever occurred first assessed up to 67 months There were no deaths. All participants survived.
Endocrine disorders Hyperglycemia	22.7% 5/22 • Number of events 5 • Adverse events collected from the initiation of study drugs until disease progression, death, unacceptable toxicity, or withdraw of study consent, whichever occurred first assessed up to 67 months There were no deaths. All participants survived.
Infections and infestations Infection	18.2% 4/22 • Number of events 4 • Adverse events collected from the initiation of study drugs until disease progression, death, unacceptable toxicity, or withdraw of study consent, whichever occurred first assessed up to 67 months There were no deaths. All participants survived.
Hepatobiliary disorders ALT elevation	13.6% 3/22 • Number of events 3 • Adverse events collected from the initiation of study drugs until disease progression, death, unacceptable toxicity, or withdraw of study consent, whichever occurred first assessed up to 67 months There were no deaths. All participants survived.
General disorders Anorexia	9.1% 2/22 • Number of events 2 • Adverse events collected from the initiation of study drugs until disease progression, death, unacceptable toxicity, or withdraw of study consent, whichever occurred first assessed up to 67 months There were no deaths. All participants survived.
General disorders Insomnia(grade 2)	9.1% 2/22 • Number of events 2 • Adverse events collected from the initiation of study drugs until disease progression, death, unacceptable toxicity, or withdraw of study consent, whichever occurred first assessed up to 67 months There were no deaths. All participants survived.
Skin and subcutaneous tissue disorders Rash (grade 2)	9.1% 2/22 • Number of events 2 • Adverse events collected from the initiation of study drugs until disease progression, death, unacceptable toxicity, or withdraw of study consent, whichever occurred first assessed up to 67 months There were no deaths. All participants survived.
Blood and lymphatic system disorders Anemia(grade 2)	4.5% 1/22 • Number of events 1 • Adverse events collected from the initiation of study drugs until disease progression, death, unacceptable toxicity, or withdraw of study consent, whichever occurred first assessed up to 67 months There were no deaths. All participants survived.
Respiratory, thoracic and mediastinal disorders Dyspnea(grade 2)	4.5% 1/22 • Number of events 1 • Adverse events collected from the initiation of study drugs until disease progression, death, unacceptable toxicity, or withdraw of study consent, whichever occurred first assessed up to 67 months There were no deaths. All participants survived.
Psychiatric disorders Depression	4.5% 1/22 • Number of events 1 • Adverse events collected from the initiation of study drugs until disease progression, death, unacceptable toxicity, or withdraw of study consent, whichever occurred first assessed up to 67 months There were no deaths. All participants survived.
General disorders Fever(grade 2)	4.5% 1/22 • Number of events 1 • Adverse events collected from the initiation of study drugs until disease progression, death, unacceptable toxicity, or withdraw of study consent, whichever occurred first assessed up to 67 months There were no deaths. All participants survived.
Musculoskeletal and connective tissue disorders Generalized muscle weakness(grade 2)	4.5% 1/22 • Number of events 1 • Adverse events collected from the initiation of study drugs until disease progression, death, unacceptable toxicity, or withdraw of study consent, whichever occurred first assessed up to 67 months There were no deaths. All participants survived.

Additional Information

Dr. Vicente Valero, MD/ Professor, Breast Medical Oncology

UT MD Anderson Cancer Center

Phone: 713- 563-0751

Email: vvalero@mdanderson.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place