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

NCT04256941 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 2018-0287NCI-2019-08825
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well letrozole, anastrozole, or fulvestrant work when given together with ribociclib, palbociclib, and/or abemaciclib in treating patients with hormone receptor (HR) positive breast cancer that has spread to other places in the body (metastatic) and has an ERS1 activating mutation. Letrozole, anastrozole, ribociclib, palbociclib, and abemaciclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Estrogen can cause the growth of breast cancer cells. Hormone therapy using fulvestrant may fight breast cancer by blocking the use of estrogen by the tumor cells. It is not yet known if giving letrozole, anastrozole, or fulvestrant with ribociclib, palbociclib, and/or abemaciclib will work better in treating patients with breast cancer.

Conditions

Anatomic Stage IV Breast Cancer AJCC v8; Metastatic Breast Carcinoma; Prognostic Stage IV Breast Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS)

  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.

  Up to 30 days

Secondary Outcomes (5)

• Circulating Tumor Deoxyribonucleic Acid (ctDNA) ESR1 Mutant Allele Fraction (MAF) and Kinetics

  Up to 30 days

• Prevalence of Emergence of Estrogen Receptor 1 (ESR1) Mutations

  Up to 30 days

• Changes in Cancer Antigens (CA) 15-3 Tumor Marker

  Up to 30 days

• Overall Survival (OS)

  Up to 30 days

• Time to Next Treatment

  Up to 30 days

Study Arms (2)

Arm I (ribociclib, palbociclib, abemaciclib, fulvestrant)

EXPERIMENTAL

Patients receive ribociclib PO QD, palbociclib PO QD on days 1-21, and/or abemaciclib PO BID on days 1-28. Patients also receive fulvestrant IM for 2 injections over 1-2 minutes each on days 1 and 15 of cycle 1 and day 2 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Abemaciclib; Drug: Fulvestrant; Drug: Palbociclib; Drug: Ribociclib

Arm II (ribociclib, palbociclib, abemaciclib, letrozole)

ACTIVE COMPARATOR

Patients receive ribociclib orally PO QD, palbociclib PO QD on days 1-21, and/or abemaciclib PO BID on days 1-28. Patients also receive letrozole PO QD or anastrozole PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Abemaciclib; Drug: Anastrozole; Drug: Letrozole; Drug: Palbociclib; Drug: Ribociclib

Interventions

Abemaciclib DRUG

Given PO

Also known as: LY-2835219, LY2835219, Verzenio

Arm I (ribociclib, palbociclib, abemaciclib, fulvestrant); Arm II (ribociclib, palbociclib, abemaciclib, letrozole)

Anastrozole DRUG

Given PO

Also known as: Anastrazole, Arimidex, ICI D1033, ICI-D1033, ZD-1033

Arm II (ribociclib, palbociclib, abemaciclib, letrozole)

Fulvestrant DRUG

Given IM

Also known as: Faslodex, Faslodex(ICI 182,780), ICI 182,780, ICI 182780, ZD9238

Arm I (ribociclib, palbociclib, abemaciclib, fulvestrant)

Letrozole DRUG

Given PO

Also known as: CGS 20267, Femara

Arm II (ribociclib, palbociclib, abemaciclib, letrozole)

Palbociclib DRUG

Given PO

Also known as: 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-8h-pyrido(2,3-d)pyrimidin-7-one, Ibrance, PD 0332991, PD 332991, PD 991, PD-0332991

Arm I (ribociclib, palbociclib, abemaciclib, fulvestrant); Arm II (ribociclib, palbociclib, abemaciclib, letrozole)

Ribociclib DRUG

Given PO

Also known as: Kisqali, LEE-011, LEE011

Arm I (ribociclib, palbociclib, abemaciclib, fulvestrant); Arm II (ribociclib, palbociclib, abemaciclib, letrozole)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L
• Platelets \>= 50 x 10\^9/L
• Hemoglobin (Hb) \>= 9 g/dL
• Total serum bilirubin =\< 2.0 mg/dL
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 2.5 x upper limit of normal (ULN) (=\< 5 x ULN in patients with liver metastases)
• Serum creatinine =\< 1.5 x ULN
• Activating ESR1 mutation (e.g. D538G, Y537S/N, S463P) identified on ctDNA. Novel ESR1 alterations allowed as per discretion of principal investigator (PI)
• On AI with CDK4/6 inhibitor (palbociclib, ribociclib, or abemaciclib) as first line therapy for metastatic breast cancer (MBC) for at least 12 months without evidence of clinical progression
• Patients with histologically confirmed HR positive (estrogen receptor \[ER\] positive \[+\] and/or progesterone receptor \[PR\]+ \[\> 10%\]), MBC

You may not qualify if:

• Pregnant or lactating women
• Received prior therapy for MBC (except for AI use for up to 4 weeks prior to initiation of CDK4/6 inhibitor)
• Prior therapy with fulvestrant in the metastatic setting
• Corrected QT (QTc) interval \> 480 msec, Brugada syndrome or known history of QTc prolongation or Torsade de Pointes
• Psychiatric illness which would limit informed consent
• Patients with de novo metastatic disease
• Patients who have 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, or any other clinically significant cardiac disease, active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, and active and chronic hepatitis (i.e. quantifiable hepatitis B virus \[HBV\]-DNA and/or positive hepatitis B surface antigen \[HbsAg\], quantifiable hepatitis C virus \[HCV\]-ribonucleic acid \[RNA\]), severe hepatic impairment (Child-Pugh C)
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy
• Expected survival \< 6 months
• Any serious medical illness, other than that treated by this study, which would limit survival to less than 1 month
• Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable or will not be able to complete the entire study
• Patients who are currently part of or have participated in any clinical investigation with an investigational drug within 1 month prior to dosing
• Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, must use highly effective methods of contraception during the study and 8 weeks after the end of treatment. Highly effective contraception methods include combination of any two of the following: placement of an intrauterine device (IUD) or intrauterine system (IUS); barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository; total abstinence or; male/female sterilization
• Male patients whose sexual partner(s) are WOCBP who are not willing to use adequate contraception, during the study and for 8 weeks after the end of treatment

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Breast Neoplasms

Interventions

abemaciclib; Anastrozole; Fulvestrant; Letrozole; palbociclib; ribociclib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Dr. Senthil Damodaran
• Organization: University of Texas M D Anderson Cancer Center

sdamodaran@mdanderson.org

713-792-2817

Study Officials

• Senthilkumar Damodaran, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2020
• First Posted: February 5, 2020
• Study Start: May 31, 2019
• Primary Completion: September 22, 2023
• Study Completion: September 22, 2023
• Last Updated: December 27, 2024
• Results First Posted: December 27, 2024

Record last verified: 2024-12

Locations

US (1)