Trial Outcomes & Findings for Exemestane in Combination With Fulvestrant in Postmenopausal Women With Hormone Sensitive Advanced Breast Cancer (NCT NCT00201864)

NCT ID: NCT00201864

Last Updated: 2018-07-26

Results Overview

TTP is defined as the time from first treatment to objective evidence of progression on the basis of radiological evaluation and/or physical exam (if physical examination identifies a site of measurable disease). 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

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

40 participants

Primary outcome timeframe

Every 2 cycles up to 2 years

Results posted on

2018-07-26

Participant Flow

Patients were enrolled between November 2005 and December 2009

Participant milestones

Participant milestones
Measure	Exemestane and Fulvestrant Combination of daily exemestane 25 mg with monthly 250 mg Fulvestrant injection Exemestane: 25 mg orally per day Fulvestrant: 250 mg IM starting on Day 8 and then every 28 days.
Overall Study STARTED	40
Overall Study COMPLETED	40
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Exemestane in Combination With Fulvestrant in Postmenopausal Women With Hormone Sensitive Advanced Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Exemestane and Fulvestrant n=40 Participants Combination of daily exemestane 25 mg with monthly 250 mg Fulvestrant injection Exemestane: 25 mg orally per day Fulvestrant: 250 mg IM starting on Day 8 and then every 28 days.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	29 Participants n=5 Participants
Age, Categorical >=65 years	11 Participants n=5 Participants
Age, Continuous	58 years n=5 Participants
Sex: Female, Male Female	40 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	40 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	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	4 Participants n=5 Participants
Race (NIH/OMB) White	36 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	40 participants n=5 Participants
Time From Primary Diagnosis to Metastatic Disease	5 years n=5 Participants
Relapse and/or Progression During adjuvant endocrine therapy	14 participants n=5 Participants
Relapse and/or Progression >12 mo after completion adjuvant therapy	9 participants n=5 Participants
Relapse and/or Progression Presenting with de novo metastatic disease	8 participants n=5 Participants
Relapse and/or Progression Never on adjuvant hormonal therapy	9 participants n=5 Participants

PRIMARY outcome

Timeframe: Every 2 cycles up to 2 years

Outcome measures

Outcome measures
Measure	Exemestane and Fulvestrant n=40 Participants Combination of daily exemestane 25 mg with monthly 250 mg Fulvestrant injection Exemestane: 25 mg orally per day Fulvestrant: 250 mg IM starting on Day 8 and then every 28 days.	IGFBP-3 IGFBP-3-insulin-like growth factor-binding
Time to Progression (TTP) in Women With Hormone Responsive Advanced Breast Cancer Treated With Combination of Exemestane and Fulvestrant.	6.9 months Interval 3.9 to 13.5	—

SECONDARY outcome

Timeframe: Every 2 cycles, up to 1 year

Response and progression was evaluated after every 2 cycles by physical examination and imaging studies using the international RECIST criteria. Complete Response (CR), Partial Response (PR), Overall Response Rate (ORR), Stable Disease (SD), Progressive Disease (PD). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI and/or CT: Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progressive Disease (PD); PD, 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; Complete Response (CR), Disappearance of all target lesions; Overall Response Rate (ORR), CR+PR

Outcome measures

Outcome measures
Measure	Exemestane and Fulvestrant n=40 Participants Combination of daily exemestane 25 mg with monthly 250 mg Fulvestrant injection Exemestane: 25 mg orally per day Fulvestrant: 250 mg IM starting on Day 8 and then every 28 days.	IGFBP-3 IGFBP-3-insulin-like growth factor-binding
Overall Clinical Benefit (Complete Response Rate, Partial Response and Stable Disease) CR	0 patients	—
Overall Clinical Benefit (Complete Response Rate, Partial Response and Stable Disease) PR	3 patients	—
Overall Clinical Benefit (Complete Response Rate, Partial Response and Stable Disease) Overall Clinical Benefit	20 patients	—
Overall Clinical Benefit (Complete Response Rate, Partial Response and Stable Disease) PD	12 patients	—
Overall Clinical Benefit (Complete Response Rate, Partial Response and Stable Disease) ORR	3 patients	—
Overall Clinical Benefit (Complete Response Rate, Partial Response and Stable Disease) SD ≥ 6 Mo	17 patients	—
Overall Clinical Benefit (Complete Response Rate, Partial Response and Stable Disease) SD< 6 Mo	8 patients	—

SECONDARY outcome

Timeframe: Day 7 and Day 120

Population: Only 9 patients had evaluable PK data collected and analyzed

5 mL of venous whole blood was obtained before dosing and then at 1, 2, 4, 6, 8, and 24 hours after exemestane ingestion on each of the 2 time points.

Outcome measures

Outcome measures
Measure	Exemestane and Fulvestrant n=9 Participants Combination of daily exemestane 25 mg with monthly 250 mg Fulvestrant injection Exemestane: 25 mg orally per day Fulvestrant: 250 mg IM starting on Day 8 and then every 28 days.	IGFBP-3 IGFBP-3-insulin-like growth factor-binding
Maximum Plasma Concentration (Cmax) of Exemestane When Administered Alone and With Fulvestrant Exemestane Alone (Day 7)	20.1 ng/ml Standard Deviation 7.7	—
Maximum Plasma Concentration (Cmax) of Exemestane When Administered Alone and With Fulvestrant Exemestane + Fulvestrant (Day 120)	21.2 ng/ml Standard Deviation 11.1	—

SECONDARY outcome

Timeframe: Prestudy, Day 7 and Day 120

Population: Increase in mean levels from baseline to day 120. Not all patients had the IGF-1 and IGFBP-3 levels present.

Outcome measures

Outcome measures
Measure	Exemestane and Fulvestrant n=23 Participants Combination of daily exemestane 25 mg with monthly 250 mg Fulvestrant injection Exemestane: 25 mg orally per day Fulvestrant: 250 mg IM starting on Day 8 and then every 28 days.	IGFBP-3 n=22 Participants IGFBP-3-insulin-like growth factor-binding
Examine the Effect of Exemestane + Fulvestrant on Serum IGF-1 and IGFPB-3 Levels Baseline	119 ng/mL Standard Deviation 41.1	4946 ng/mL Standard Deviation 1188
Examine the Effect of Exemestane + Fulvestrant on Serum IGF-1 and IGFPB-3 Levels Day 7	141 ng/mL Standard Deviation 55.1	5273 ng/mL Standard Deviation 1372
Examine the Effect of Exemestane + Fulvestrant on Serum IGF-1 and IGFPB-3 Levels Day 120	161 ng/mL Standard Deviation 61.2	5537 ng/mL Standard Deviation 1166

Adverse Events

Single-arm Study

Serious events: 6 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Single-arm Study n=40 participants at risk Combination of daily exemestane 25 mg with monthly 250 mg Fulvestrant injection Exemestane: 25 mg orally per day Fulvestrant: 250 mg IM starting on Day 8 and then every 28 days.
General disorders Chest pain	2.5% 1/40 • Number of events 1 The NCI Common Terminology Criteria for Adverse Events (CTCAE) v3.0 was used to assess adverse events for patients on this trial. The CTCAE using is a descriptive terminology that utilizes Adverse Event (AE) reporting.
Vascular disorders Thromboembolism	5.0% 2/40 • Number of events 2 The NCI Common Terminology Criteria for Adverse Events (CTCAE) v3.0 was used to assess adverse events for patients on this trial. The CTCAE using is a descriptive terminology that utilizes Adverse Event (AE) reporting.
Gastrointestinal disorders Nausea	2.5% 1/40 • Number of events 1 The NCI Common Terminology Criteria for Adverse Events (CTCAE) v3.0 was used to assess adverse events for patients on this trial. The CTCAE using is a descriptive terminology that utilizes Adverse Event (AE) reporting.
Gastrointestinal disorders Vomiting	2.5% 1/40 • Number of events 1 The NCI Common Terminology Criteria for Adverse Events (CTCAE) v3.0 was used to assess adverse events for patients on this trial. The CTCAE using is a descriptive terminology that utilizes Adverse Event (AE) reporting.
Metabolism and nutrition disorders Hypercalcemia	2.5% 1/40 • Number of events 1 The NCI Common Terminology Criteria for Adverse Events (CTCAE) v3.0 was used to assess adverse events for patients on this trial. The CTCAE using is a descriptive terminology that utilizes Adverse Event (AE) reporting.

Other adverse events

Other adverse events
Measure	Single-arm Study n=40 participants at risk Combination of daily exemestane 25 mg with monthly 250 mg Fulvestrant injection Exemestane: 25 mg orally per day Fulvestrant: 250 mg IM starting on Day 8 and then every 28 days.
Blood and lymphatic system disorders Neutropenia	2.5% 1/40 • Number of events 1 The NCI Common Terminology Criteria for Adverse Events (CTCAE) v3.0 was used to assess adverse events for patients on this trial. The CTCAE using is a descriptive terminology that utilizes Adverse Event (AE) reporting.
Blood and lymphatic system disorders Anemia	10.0% 4/40 • Number of events 4 The NCI Common Terminology Criteria for Adverse Events (CTCAE) v3.0 was used to assess adverse events for patients on this trial. The CTCAE using is a descriptive terminology that utilizes Adverse Event (AE) reporting.
Injury, poisoning and procedural complications Thrombocytopenia	5.0% 2/40 • Number of events 2 The NCI Common Terminology Criteria for Adverse Events (CTCAE) v3.0 was used to assess adverse events for patients on this trial. The CTCAE using is a descriptive terminology that utilizes Adverse Event (AE) reporting.
General disorders Fatigue	35.0% 14/40 • Number of events 14 The NCI Common Terminology Criteria for Adverse Events (CTCAE) v3.0 was used to assess adverse events for patients on this trial. The CTCAE using is a descriptive terminology that utilizes Adverse Event (AE) reporting.
Musculoskeletal and connective tissue disorders Arthralgia	15.0% 6/40 • Number of events 6 The NCI Common Terminology Criteria for Adverse Events (CTCAE) v3.0 was used to assess adverse events for patients on this trial. The CTCAE using is a descriptive terminology that utilizes Adverse Event (AE) reporting.
Gastrointestinal disorders Nausea	10.0% 4/40 • Number of events 4 The NCI Common Terminology Criteria for Adverse Events (CTCAE) v3.0 was used to assess adverse events for patients on this trial. The CTCAE using is a descriptive terminology that utilizes Adverse Event (AE) reporting.
Gastrointestinal disorders Vomiting	10.0% 4/40 • Number of events 4 The NCI Common Terminology Criteria for Adverse Events (CTCAE) v3.0 was used to assess adverse events for patients on this trial. The CTCAE using is a descriptive terminology that utilizes Adverse Event (AE) reporting.
Metabolism and nutrition disorders Anorexia	15.0% 6/40 • Number of events 6 The NCI Common Terminology Criteria for Adverse Events (CTCAE) v3.0 was used to assess adverse events for patients on this trial. The CTCAE using is a descriptive terminology that utilizes Adverse Event (AE) reporting.
Respiratory, thoracic and mediastinal disorders Dyspnea	5.0% 2/40 • Number of events 2 The NCI Common Terminology Criteria for Adverse Events (CTCAE) v3.0 was used to assess adverse events for patients on this trial. The CTCAE using is a descriptive terminology that utilizes Adverse Event (AE) reporting.
Musculoskeletal and connective tissue disorders Bone pain	25.0% 10/40 • Number of events 10 The NCI Common Terminology Criteria for Adverse Events (CTCAE) v3.0 was used to assess adverse events for patients on this trial. The CTCAE using is a descriptive terminology that utilizes Adverse Event (AE) reporting.

Additional Information

Ewa Mrozek

The Ohio State University

Phone: 614-293-7956

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place