Genetic Testing for Aromatase Inhibitor-Related Musculoskeletal Disorders

Recruiting at 1 trial location

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: ECOG-ACRIN Cancer Research Group

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

1046 Participants Needed

Trial Summary

What is the purpose of this trial?

E1Z11 is a study to determine whether certain genetic information can predict which breast cancer patients will discontinue treatment with aromatase inhibitors (AIs) due to the development of musculoskeletal symptoms (MSS). Women with stage I-III breast cancer who are prescribed the aromatase inhibitor anastrozole as treatment may join.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently taking daily pain medications for chronic conditions. Low dose aspirin is allowed.

Is Anastrozole (Arimidex) generally safe for humans?

Aromatase inhibitors like Anastrozole can cause musculoskeletal side effects (joint and muscle pain) and vasomotor symptoms (hot flashes) in some patients, especially those with certain genetic variations. These side effects have been observed in breast cancer patients, and genetic testing may help identify individuals at higher risk. ^{1 2 3 4 5}

How is the drug Anastrozole unique in treating musculoskeletal disorders related to aromatase inhibitors?

Anastrozole is unique because it is an aromatase inhibitor that reduces estrogen levels, which can lead to musculoskeletal symptoms. The clinical trial focuses on genetic testing to predict these side effects, potentially allowing for personalized treatment plans to minimize adverse effects. ^{1 2 4 6 7}

Research Team

Vered Stearns

Principal Investigator

Eastern Cooperative Oncology Group

Eligibility Criteria

This trial is for post-menopausal women with stage I-III breast cancer that's estrogen/progesterone receptor positive. They should be planning to take anastrozole for at least a year, have pain rated less than 4 out of 10, and not have had certain prior treatments or chronic conditions needing daily pain medication.

Inclusion Criteria

I haven't had a blood clot in my legs or lungs in the last 5 years.

My breast cancer is positive for estrogen or progesterone receptors.

My liver, blood, and kidney functions are good enough for anastrozole treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive anastrozole orally once daily for 12 months

12 months

Monthly visits for monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Quarterly visits

Treatment Details

Interventions

• Anastrozole

Trial Overview The study aims to find genetic markers predicting if patients will stop using aromatase inhibitors due to musculoskeletal symptoms. It involves taking anastrozole, answering questionnaires, lab biomarker analysis, and pharmacogenomic studies.

Participant Groups

Group I: Supportive care (anastrozole) Experimental Treatment 1 Intervention

Patients receive anastrozole PO QD for 12 months.

Anastrozole is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Arimidex for:

• Breast cancer
• Early breast cancer in postmenopausal women

Approved in United States as Arimidex for:

• Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
• First-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer

Approved in Canada as Arimidex for:

• Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
• Treatment of postmenopausal women with hormone receptor-positive advanced breast cancer

Approved in Japan as Arimidex for:

• Breast cancer

Who Is Running the Clinical Trial?

ECOG-ACRIN Cancer Research Group

Lead Sponsor

Trials

122

Recruited

160,000+

Eastern Cooperative Oncology Group

Lead Sponsor

Trials

272

Recruited

153,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Germline variants in the CYP19A1 gene are related to specific adverse events in aromatase inhibitor users: a substudy of Dutch patients in the TEAM trial. [2014]

2. United States pubmed.ncbi.nlm.nih.gov

Indications of clinical and genetic predictors for aromatase inhibitors related musculoskeletal adverse events in Chinese Han women with breast cancer. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Genome-wide associations and functional genomic studies of musculoskeletal adverse events in women receiving aromatase inhibitors. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Attempted replication of SNPs in RANKL and OPG with musculoskeletal adverse events during aromatase inhibitor treatment for breast cancer. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Polymorphisms of T- cell leukemia 1A gene loci are not related to the development of adjuvant letrozole-induced adverse events in breast cancer. [2021]

6. Iran pubmed.ncbi.nlm.nih.gov

Genotype, allele and haplotype frequencies of four TCL1A gene polymorphisms associated with musculoskeletal toxicity in the South Indian descent. [2021]

7. Netherlands pubmed.ncbi.nlm.nih.gov

CYP19A1 polymorphisms and clinical outcomes in postmenopausal women with hormone receptor-positive breast cancer in the BIG 1-98 trial. [2018]