Trial Outcomes & Findings for Aromatase Inhibitor Therapy With or Without Fulvestrant for the Treatment of HR Positive Metastatic Breast Cancer With an ERS1 Activating Mutation, the INTERACT Study (NCT NCT04256941)

NCT ID: NCT04256941

Last Updated: 2024-12-27

Results Overview

Survival curves for PFS will be analyzed using the Kaplan-Meier method and survival difference across groups will be examined by log rank test. Will estimate the treatment comparison with 95% confidence intervals and p-value using Cox proportional hazards regression and we will assess the proportional hazard assumption using graphs of rescaled Schoenfeld residuals and related tests.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

4 participants

Primary outcome timeframe

Up to 30 days

Results posted on

2024-12-27

Participant Flow

Study was opened to accrual on 5/31/2019. The study was intended for patients with ESR1 mutations. Despite modifications, accrual was poor and the closed to accrual on 8/24/2023

Of the 49 patients screened, 6 patients harbored ESR1 mutation. 4 patients were randomized to the study. 1 patient withdrew consent due to frequent travel/visits after randomization (AI arm). 1 patient was a screen fail due to elevated LFTs, and 1 patient passed away prior to study intervention)

Participant milestones

Participant milestones
Measure
Fulvestrant
Fulvestrant (Faslodex), a selective estrogen receptor antagonist, was initially indicated for treatment of HR positive MBC in post-menopausal women with disease progression following prior anti-estrogen therapy.
Continuing AI After Randomization
CDK inhibitors e.g. palbociclib (Ibrance), ribociclib (Kisqali), and abemaciclib (verzenio) are approved for the first line treatment of HR positive advanced breast cancers in combination with aromatase inhibitors as well as in combination with fulvestrant with disease progression following prior endocrine therapy.
Overall Study
STARTED
1
3
Overall Study
COMPLETED
0
0
Overall Study
NOT COMPLETED
1
3

Reasons for withdrawal

Reasons for withdrawal
Measure
Fulvestrant
Fulvestrant (Faslodex), a selective estrogen receptor antagonist, was initially indicated for treatment of HR positive MBC in post-menopausal women with disease progression following prior anti-estrogen therapy.
Continuing AI After Randomization
CDK inhibitors e.g. palbociclib (Ibrance), ribociclib (Kisqali), and abemaciclib (verzenio) are approved for the first line treatment of HR positive advanced breast cancers in combination with aromatase inhibitors as well as in combination with fulvestrant with disease progression following prior endocrine therapy.
Overall Study
Withdrawal by Subject
0
1
Overall Study
Death
1
0
Overall Study
Disease Progession
0
2

Baseline Characteristics

Aromatase Inhibitor Therapy With or Without Fulvestrant for the Treatment of HR Positive Metastatic Breast Cancer With an ERS1 Activating Mutation, the INTERACT Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Fulvestrant
n=1 Participants
Fulvestrant (Faslodex), a selective estrogen receptor antagonist, was initially indicated for treatment of HR positive MBC in post-menopausal women with disease progression following prior anti-estrogen therapy.
Continuing AI After Randomization
n=3 Participants
CDK inhibitors e.g. palbociclib (Ibrance), ribociclib (Kisqali), and abemaciclib (verzenio) are approved for the first line treatment of HR positive advanced breast cancers in combination with aromatase inhibitors as well as in combination with fulvestrant with disease progression following prior endocrine therapy.
Total
n=4 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
0 Participants
n=5 Participants
2 Participants
n=7 Participants
2 Participants
n=5 Participants
Age, Categorical
>=65 years
1 Participants
n=5 Participants
1 Participants
n=7 Participants
2 Participants
n=5 Participants
Sex: Female, Male
Female
1 Participants
n=5 Participants
3 Participants
n=7 Participants
4 Participants
n=5 Participants
Sex: Female, Male
Male
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants
n=5 Participants
1 Participants
n=7 Participants
1 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
1 Participants
n=5 Participants
2 Participants
n=7 Participants
3 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
White
1 Participants
n=5 Participants
3 Participants
n=7 Participants
4 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Up to 30 days

Population: No data was collected since despite modifications, accrual was poor and the closed. Outcome Measure has zero total analyzed at the protocol specified timepoint.

Survival curves for PFS will be analyzed using the Kaplan-Meier method and survival difference across groups will be examined by log rank test. Will estimate the treatment comparison with 95% confidence intervals and p-value using Cox proportional hazards regression and we will assess the proportional hazard assumption using graphs of rescaled Schoenfeld residuals and related tests.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 30 days

Population: No data was collected since despite modifications, accrual was poor and the closed. Outcome Measure has zero total analyzed at the protocol specified timepoint.

Graphical analysis, such as scatter plots with Lowess smoothers, will be used to assess the correlative structure of outcomes and compare MAF between fulvestrant and aromatase inhibitor-treated groups. The Pearson correlation, or its non-parametric analogue, the Spearman correlation, will be used to estimate the linear correlation among variables.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 30 days

Population: No data was collected since despite modifications, accrual was poor and the closed. Outcome Measure has zero total analyzed at the protocol specified timepoint.

Will be assessed by the secondary resistance of endocrine therapy.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 30 days

Population: No data was collected since despite modifications, accrual was poor and the closed. Outcome Measure has zero total analyzed at the protocol specified timepoint.

Will correlate ctDNA with CA 15-3 tumor marker changes.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 30 days

Population: No data was collected since despite modifications, accrual was poor and the closed. Outcome Measure has zero total analyzed at the protocol specified timepoint.

Survival curves for OS will be analyzed using the Kaplan-Meier method and survival difference across groups will be examined by log rank test. Will estimate the treatment comparison with 95% confidence intervals and p-value using Cox proportional hazards regression and we will assess the proportional hazard assumption using graphs of rescaled Schoenfeld residuals and related tests.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 30 days

Population: No data was collected since despite modifications, accrual was poor and the closed. Outcome Measure has zero total analyzed at the protocol specified timepoint.

Will be assessed on next line of therapy after progression.

Outcome measures

Outcome data not reported

Adverse Events

Fulvestrant

Serious events: 0 serious events
Other events: 1 other events
Deaths: 1 deaths

Continuing AI After Randomization

Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Fulvestrant
n=1 participants at risk
CDK inhibitors e.g. palbociclib (Ibrance), ribociclib (Kisqali), and abemaciclib (verzenio) are approved for the first line treatment of HR positive advanced breast cancers in combination with aromatase inhibitors as well as in combination with fulvestrant with disease progression following prior endocrine therapy.
Continuing AI After Randomization
n=3 participants at risk
CDK inhibitors e.g. palbociclib (Ibrance), ribociclib (Kisqali), and abemaciclib (verzenio) are approved for the first line treatment of HR positive advanced breast cancers in combination with aromatase inhibitors as well as in combination with fulvestrant with disease progression following prior endocrine therapy.
Blood and lymphatic system disorders
Anemia
100.0%
1/1 • 50 months and 3 weeks
33.3%
1/3 • 50 months and 3 weeks
Musculoskeletal and connective tissue disorders
Back Pain
100.0%
1/1 • 50 months and 3 weeks
0.00%
0/3 • 50 months and 3 weeks
General disorders
Blurred Vision
100.0%
1/1 • 50 months and 3 weeks
0.00%
0/3 • 50 months and 3 weeks
Gastrointestinal disorders
Constipation
100.0%
1/1 • 50 months and 3 weeks
0.00%
0/3 • 50 months and 3 weeks
General disorders
Cough
100.0%
1/1 • 50 months and 3 weeks
0.00%
0/3 • 50 months and 3 weeks
Musculoskeletal and connective tissue disorders
Fall
100.0%
1/1 • 50 months and 3 weeks
0.00%
0/3 • 50 months and 3 weeks
Metabolism and nutrition disorders
Hyperglycemia
100.0%
1/1 • 50 months and 3 weeks
33.3%
1/3 • 50 months and 3 weeks
Blood and lymphatic system disorders
ALT increased
0.00%
0/1 • 50 months and 3 weeks
66.7%
2/3 • 50 months and 3 weeks
Blood and lymphatic system disorders
Alkaline Phosphatase increased
0.00%
0/1 • 50 months and 3 weeks
33.3%
1/3 • 50 months and 3 weeks
General disorders
Allergic Rhinitis
0.00%
0/1 • 50 months and 3 weeks
33.3%
1/3 • 50 months and 3 weeks
Blood and lymphatic system disorders
AST increased
0.00%
0/1 • 50 months and 3 weeks
66.7%
2/3 • 50 months and 3 weeks
Blood and lymphatic system disorders
Hypercalcemia
0.00%
0/1 • 50 months and 3 weeks
33.3%
1/3 • 50 months and 3 weeks
Blood and lymphatic system disorders
Hyponatremia
100.0%
1/1 • 50 months and 3 weeks
33.3%
1/3 • 50 months and 3 weeks
Musculoskeletal and connective tissue disorders
Joint Effusion
0.00%
0/1 • 50 months and 3 weeks
33.3%
1/3 • 50 months and 3 weeks
Blood and lymphatic system disorders
Neutrophil count decreased
100.0%
1/1 • 50 months and 3 weeks
66.7%
2/3 • 50 months and 3 weeks
Blood and lymphatic system disorders
White blood cell decreased
100.0%
1/1 • 50 months and 3 weeks
33.3%
1/3 • 50 months and 3 weeks
General disorders
Vomiting
100.0%
1/1 • 50 months and 3 weeks
0.00%
0/3 • 50 months and 3 weeks
Blood and lymphatic system disorders
Lymphocyte count decreased
100.0%
1/1 • 50 months and 3 weeks
0.00%
0/3 • 50 months and 3 weeks
Blood and lymphatic system disorders
Creatinine increased
100.0%
1/1 • 50 months and 3 weeks
33.3%
1/3 • 50 months and 3 weeks

Additional Information

Dr. Senthil Damodaran

University of Texas M D Anderson Cancer Center

Phone: 713-792-2817

Results disclosure agreements

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