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Prospective Study of UDP-gluconoryltransferase (UGT) 2B17 Genotype as a Predictive Marker of Exemestane Pharmacokinetics and Pharmacodynamics in Asian Women With Hormone Receptor-positive Advanced Breast Cancer

21 Years
Open (Enrolling)
Breast Carcinoma

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Trial Information

Prospective Study of UDP-gluconoryltransferase (UGT) 2B17 Genotype as a Predictive Marker of Exemestane Pharmacokinetics and Pharmacodynamics in Asian Women With Hormone Receptor-positive Advanced Breast Cancer

This is a prospective non-randomised open-label study of exemestane in post-menopausal,
hormone receptor positive advanced breast cancer patients, with pre-specified analysis of
exemestane pharmacokinetics and pharmacodynamics according to UGT2B17 genotype (UGT2B17*2/*2
versus those with at least one wild-type allele). A total of 110 patients will be enrolled
over a period of 30 months. Eligible patients will receive exemestane 25mg daily orally (as
part of standard care) until progression of disease or intolerable toxicities. At the time
of study entry, blood samples will be drawn for genotyping studies (for research purposes)
but investigators will be blinded to the results. Pharmacokinetic sampling for exemestane
and its metabolites will be performed at baseline and on day 29 (+/- 3 days) before dosing
and 0.5, 1, 2, 4, 6, 8 and 24 hours after exemestane ingestion. Patients will be evaluated
on an 8-weekly basis for toxicities and efficacy assessments during the first 6 months of
treatment, followed by 12-weekly thereafter until disease progression, unacceptable
toxicities, or patient withdrawal.

Inclusion Criteria:

- Female, Age ≥ 21 years

- Histologically-proven hormone-receptor positive metastatic breast carcinoma

- A minimum of one prior line of endocrine therapy in the metastatic setting.
First-line therapy is permitted if the patient relapses while on or within 6 months
of adjuvant endocrine therapy.

- Patients with both measurable and non-measurable disease as per the Response
Evaluation Criteria In Solid Tumours (RECIST) v1.1 may be enrolled.

- Eastern co-operative group (ECOG) performance status of < 2 and estimated life
expectancy of at least 12 weeks

- Post-menopausal women* or pre-menopausal women on ovarian suppression with FSH and
plasma oestradiol levels in menopausal range within 21 days of study enrollment

- Adequate organ function including the following:

Bone marrow:

- Absolute neutrophil (segmented and bands) count (ANC) ≥ 1.5 x 109/L

- Platelets ≥ 100 x 109/L


- Bilirubin ≤ 1.5 x upper limit of normal (ULN),

- ALT and AST ≤ 2.5x ULN


o Calculated creatinine clearance >35ml/minute

- Signed informed consent from patient or legal representative

- Pre-menopausal females must have a negative serum pregnancy test within 21 days of
study enrollment

Exclusion Criteria:

- Concurrent administration of other anti-tumor therapies, including cytotoxic
chemotherapy, hormonal therapy, and immunotherapy are prohibited. Concomitant
bisphosphonates and gonadotropin-releasing hormone therapy are allowed.

- Patients must have recovered from the toxicities of the previous anti-cancer therapy.

- Second primary malignancy that is clinically detectable at the time of consideration
for study enrollment.

- Prior use of exemestane in the metastatic setting or relapse while on adjuvant
exemestane or within 6 months of completing adjuvant exemestane.

- Major surgery within 28 days of study drug administration.

- Concomitant use of potent CYP3A4 inducers (Table 1, section 3.5.3); a washout period
of 14 days is required for patients discontinuing these medications prior to study

- Active infection that in the opinion of the investigator would compromise the
patient's ability to tolerate therapy.

- Pregnancy.

- Breast feeding.

- Serious concomitant disorders that would compromise the safety of the patient or
compromise the patient's ability to complete the study, at the discretion of the

- Symptomatic brain metastasis.

Type of Study:


Study Design:

Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Correlation of UGT2B17*2 deletion genotype with clinical benefit rate (CBR)

Outcome Description:

The correlation of genotype (UGT2B17 *2/*2 versus those with at least one wild-type allele) with clinical benefit rate (CBR), defined as the percentage achieving CR, PR and SD in patients with measurable disease or the absence of disease progression in patients with non-measurable disease, lasting at least 24 weeks.

Outcome Time Frame:

24 weeks

Safety Issue:


Principal Investigator

Andrea LA Wong, MBBS

Investigator Role:

Principal Investigator

Investigator Affiliation:

National University Hospital, Singapore


Singapore: Domain Specific Review Boards

Study ID:




Start Date:

August 2012

Completion Date:

August 2016

Related Keywords:

  • Breast Carcinoma
  • hormone receptor positive
  • breast cancer
  • Breast Neoplasms
  • Carcinoma