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CYP2D6 PolymorphismPhase 3STEPNCT03137368

A Study to Evaluate Exemestane Tablets Combined With Ovarian Function Suppression/Ablation in Treatment of Premenopausal Breast Cancer Patients With CYP2D6*10 Mutations (STEP)

A Phase 3 study testing Exemestane Tablets, ovarian function suppression/ablation and CYP2D6*10 gene test in people with CYP2D6 Polymorphism, run by Cancer Institute and Hospital, Chinese Academy of Medical Sciences at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This is a multicenter, randomized, open-label, parallel, active-controlled superiority clinical study conducted in early premenopausal estrogen-receptor positive breast cancer patients with CYP2D6*10 mutations. Read more about this study

Who is it for?
Any age, women only
Conditions the study is for
CYP2D6 Polymorphism
What is being tested?
Exemestane Tablets, ovarian function suppression/ablation and CYP2D6*10 gene test
Could I receive a placebo?
No, everyone receives an active treatment
How many people
300 participants
Where
1 siteChina
Study dates
9 Aug 2018to 30 Oct 2023
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • Women only
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Providing informed consent forms voluntarily before screening evaluation;
  • For Chinese premenopausal women, her estradiol level must be within the premenopausal level, or the patient meet the following 4 criteria in the prior 6 months: No chemotherapy, Regular menstruation, No use of hormonal, contraceptives, No use of hormone for treatment or for temporary amenorrhea caused by chemotherapy, the estradiol level tested within 8 months after the last dose of chemotherapeutics is within the premenopausal level;
  • Patients with invasive breast cancer which has been confirmed by histological examination;
  • Complete removal of tumor by surgery without local residual;
  • Neoadjuvant chemotherapy before surgery is permitted if the surgery for primary breast cancer is performed within 12 weeks without any further adjuvant chemotherapy, or adjuvant chemotherapy is completed within 8 months;
  • Estrogen receptor (ER) and/or progesterone receptor (PR) positive: If the patient has more than one breast tumor lesions, each tumor lesion should be ER and/or PR positive.
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  • Her-2 negative;
  • Genotyping test performed by the central laboratory designated by sponsor with the results confirmed as CYP2D6*10T/T gene mutation.
  • Women of childbearing age with negative serum pregnancy test result, and agreeing to adopt highly efficient non-hormonal contraception measure throughout the study;
  • Subject without major organ dysfunction, and with normal heart, liver, kidney, lung and other major organ function.

Who cannot join

  • Inflammatory breast cancer;
  • Breast cancer patients with supraclavicular lymph nodes metastasis;
  • Patients with enlarged internal mammary lymph nodes (except for patients with negative pathologic findings);
  • Ovariectomy which is not specified in the study;
  • Patients with ovary protection during the chemotherapy;
  • Concomitant use of other aromatase inhibitors (not Exemestane);
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  • Received major surgery which was unrelated to breast cancer within four weeks before randomization, or the patients had not yet fully recovered from such surgery;
  • Pregnant or lactating women;
  • Known active hepatitis B or hepatitis C or HIV;
  • Having difficulty in swallowing oral preparations and gastrointestinal dysfunction;
  • Recently had severe and uncontrolled systemic diseases (e.g.: cardiovascular disease, lung disease, or metabolic disease, venous thrombosis with clinical significance);
  • Currently or previously suffering from other malignant tumors (except for skin basal cell carcinoma or squamous cell carcinoma, carcinoma in situ of cervix which had been fully treated), unless a radical treatment had been done with the evidence of no-recurrence or metastasis in nearly five years;
  • Allergic to any study drug or any ingredients of drug;
  • Patient with poor compliance or other conditions which makes the patient unsuitable to participate in this study judged by the investigator.

Trial locations and contacts

1 site in 1 country.

China1 site
  • CancerIHCAMS

    Beijing, Beijing Municipality, 100010

Other trials in China

About this study

Official title: A Randomized Controlled Study to Evaluate Exemestane Tablets Combined With Ovarian Function Suppression/Ablation in Treatment of Premenopausal Breast Cancer Patients With CYP2D6*10 Mutations (STEP)

This is a multicenter, randomized, open-label, parallel, active-controlled superiority clinical study conducted in early premenopausal estrogen-receptor positive breast cancer patients with CYP2D6*10 mutations. The efficacy and safety of Exemestane Tablets combined with ovarian function suppression/ablation and Tamoxifen Tablets combined with ovarian function suppression/ablation in the treatment of early premenopausal estrogen-receptor positive breast cancer patients with CYP2D6*10 mutations are compared.

Read the detailed description

The target population for this study is early stage premenopausal estrogen-receptor positive breast cancer patients with CYP2D6*10 mutations. All the potential subjects must provide the informed consent. The subjects who provide the informed consent form (ICF) will enter the screening period, and will be evaluated for the eligibility.

This study expects to enroll 300 subjects, eligible subjects will be randomized at a ratio of 1:1 into treatment group (Exemestane Tablets combined with ovarian function suppression/ablation) or control group (Tamoxifen Tablets combined with ovarian function suppression/ablation).

The subjects who are assigned to treatment group will receive Exemestane Tablet combined with ovarian function suppression/ablation, Exemestane Tablets orally, once a day, one tablet each time (25 mg) and to be taken within 8 weeks from receiving ovarian function suppression treatment or after bilateral ovariectomy, and continue for 5 years or until endpoint event occurs. If the patients are not treated for 5 years because of adverse events (AE) or other reasons, the patient should be followed up until 5 years.

The subjects who are assigned to the control group will receive Tamoxifen Tablets combined with ovarian function suppression/ablation, Tamoxifen Tablets orally, twice a day, one tablet each time (10mg) and to be taken within 8 weeks from receiving ovarian function suppression treatment or after bilateral ovariectomy, and continue for 5 years or until endpoint event occurs. If the patients are not treated for 5 years because of adverse events (AE) or other reasons, the patient should be followed up until 5 years.

The treatment regimen of ovarian function suppression/ablation is as follows: Gonadotropin-releasing hormone analogue Goserelin Injection 3.6mg or Leuprorelin Injection 3.75 mg, a subcutaneous injection will be done every 28±2 days, or bilateral ovariectomy.

According to clinical practice of adjuvant endocrine therapy for Chinese patients with breast cancer, safety and effectiveness of all patients will be evaluated once every 3 months within 2 years after receiving the study treatment, every 6 months in 3 and 4 years, every 12 months in 5 years and 30 days after treatment discontinuation. After randomization, all patients should be regularly checked for signs, symptoms, and evidence of disease recurrence by collecting their medical history, physical examination, and local examination of the breast (specialized physical examination and/or imaging examination). Patients are advised to take a bone mineral density test once a year within five years from 6 months after randomization, and receive calcium or phosphate correspondingly based on the condition. Throughout the study, the adverse events need to be closely monitored, and the frequency and severity of adverse events are recorded as well.

The study results will be statistically analyzed after the study to compare the efficacy and safety variables between the two groups, thus, the superiority of Exemestane Tablets combined with ovarian function suppression/ablation to Tamoxifen Tablets combined with ovarian function suppression/ablation in disease-free survival (DFS) will be demonstrated. Stratified analyses according to lymph-node status and age.

Being tested
Exemestane Tablets, ovarian function suppression/ablation, CYP2D6*10 gene test, Tamoxifen
Keywords
ovarian function suppression/ablation, breast cancer, Exemestane, Tamoxifen, CYP2D6*10 mutations
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Exemestane TabletsDrug

    drug therapy

  • ovarian function suppression/ablationOther

    Gonadotropin-releasing hormone analogue Goserelin Injection 3.6mg or Leuprorelin Injection 3.75 mg, a subcutaneous injection should be done every 28±2 days; or Bilateral ovariectomy.

  • CYP2D6*10 gene testGenetic

    CYP2D6*10 gene test

  • TamoxifenDrug

    drug therapy

Study groups in NCT03137368
Study groupRoleWhat they receive
treatment groupExperimentalExemestane Tablets combined with ovarian function suppression/ablation
Receives: Drug: Exemestane Tablets; Other: ovarian function suppression/ablation; Genetic: CYP2D6*10 gene test
control groupActive comparatorTamoxifen Tablets combined with ovarian function suppression/ablation
Receives: Other: ovarian function suppression/ablation; Genetic: CYP2D6*10 gene test; Drug: Tamoxifen

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Disease free survival (DFS)

    It is defined as the time from randomization to the first breast cancer local/distant recurrence, the new breast cancer of the contralateral breast, second primary cancer and the death caused by any reason

    Measured: the first breast cancer local/distant recurrence, the new breast cancer of the contralateral breast, second primary cancer and the death caused by any reason in 5 years

Secondary outcomes (3)
  1. Recurrence rate (local or distant)

    Recurrence rate (local or distant) is defined as breast cancer local or distant recurrence rate in patients from two groups

    Measured: It will be conducted once every 3 months in the first 2 years during the treatment period, every 6 months in 3 and 4 years, every 12 months in 5 years

  2. Overall survival (OS)

    OS is defined as the time from randomization to death due to any reasons

    Measured: It will be conducted once every 3 months in the first 2 years during the treatment period, every 6 months in 3 and 4 years, every 12 months in 5 years

  3. Incidence of Treatment-Emergent Adverse Events

    Results of AE/serious adverse event (SAE), clinical lab tests, 12 lead ECG, vital signs and physical examination will be evaluated throughout the study to monitor the safety of subjects

    Measured: It will be conducted once every 3 months in the first 2 years during the treatment period, every 6 months in 3 and 4 years, every 12 months in 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 May 2017
  2. Study start9 Aug 2018
  3. Primary completion30 Oct 2023 (estimated)
  4. Study completion30 Oct 2023 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
randomized, open-label, parallel, active-controlled superiority clinical study
Masking
None (open label)
Enrolment
300 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03137368
Sponsor's protocol ID
CH-BC-059
Acronym
STEP
Status last verified
Oct 2018
First submitted
24 Apr 2017
Last updated
31 Oct 2018
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Schroth W, Goetz MP, Hamann U, Fasching PA, Schmidt M, Winter S, Fritz P, Simon W, Suman VJ, Ames MM, Safgren SL, Kuffel MJ, Ulmer HU, Bolander J, Strick R, Beckmann MW, Koelbl H, Weinshilboum RM, Ingle JN, Eichelbaum M, Schwab M, Brauch H. Association between CYP2D6 polymorphisms and outcomes among women with early stage breast cancer treated with tamoxifen. JAMA. 2009 Oct 7;302(13):1429-36. doi: 10.1001/jama.2009.1420.

    PubMed 19809024
  • Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015 Jan-Feb;65(1):5-29. doi: 10.3322/caac.21254. Epub 2015 Jan 5.

    PubMed 25559415
  • Williams C, Brunskill S, Altman D, Briggs A, Campbell H, Clarke M, Glanville J, Gray A, Harris A, Johnston K, Lodge M. Cost-effectiveness of using prognostic information to select women with breast cancer for adjuvant systemic therapy. Health Technol Assess. 2006 Sep;10(34):iii-iv, ix-xi, 1-204. doi: 10.3310/hta10340.

    PubMed 16959170
  • Gansler T, Ganz PA, Grant M, Greene FL, Johnstone P, Mahoney M, Newman LA, Oh WK, Thomas CR Jr, Thun MJ, Vickers AJ, Wender RC, Brawley OW. Sixty years of CA: a cancer journal for clinicians. CA Cancer J Clin. 2010 Nov-Dec;60(6):345-50. doi: 10.3322/caac.20088.

    PubMed 21075954
  • Buzdar A. The place of chemotherapy in the treatment of early breast cancer. Br J Cancer. 1998 Sep;78 Suppl 4(Suppl 4):16-20. doi: 10.1038/bjc.1998.757.

    PubMed 9741784
  • Dezentje VO, Guchelaar HJ, Nortier JW, van de Velde CJ, Gelderblom H. Clinical implications of CYP2D6 genotyping in tamoxifen treatment for breast cancer. Clin Cancer Res. 2009 Jan 1;15(1):15-21. doi: 10.1158/1078-0432.CCR-08-2006.

    PubMed 19118028
  • Blackburn HL, Ellsworth DL, Shriver CD, Ellsworth RE. Role of cytochrome P450 genes in breast cancer etiology and treatment: effects on estrogen biosynthesis, metabolism, and response to endocrine therapy. Cancer Causes Control. 2015 Mar;26(3):319-32. doi: 10.1007/s10552-014-0519-7. Epub 2015 Jan 3.

    PubMed 25554091
  • Brauch H, Schroth W, Eichelbaum M, Schwab M, Harbeck N; in cooperation with the AGO TRAFO Comission. Clinical Relevance of CYP2D6 Genetics for Tamoxifen Response in Breast Cancer. Breast Care (Basel). 2008;3(1):43-50. doi: 10.1159/000114642. Epub 2008 Feb 22.

    PubMed 20824020
  • Jin Y, Desta Z, Stearns V, Ward B, Ho H, Lee KH, Skaar T, Storniolo AM, Li L, Araba A, Blanchard R, Nguyen A, Ullmer L, Hayden J, Lemler S, Weinshilboum RM, Rae JM, Hayes DF, Flockhart DA. CYP2D6 genotype, antidepressant use, and tamoxifen metabolism during adjuvant breast cancer treatment. J Natl Cancer Inst. 2005 Jan 5;97(1):30-9. doi: 10.1093/jnci/dji005.

    PubMed 15632378
  • Goetz MP, Rae JM, Suman VJ, Safgren SL, Ames MM, Visscher DW, Reynolds C, Couch FJ, Lingle WL, Flockhart DA, Desta Z, Perez EA, Ingle JN. Pharmacogenetics of tamoxifen biotransformation is associated with clinical outcomes of efficacy and hot flashes. J Clin Oncol. 2005 Dec 20;23(36):9312-8. doi: 10.1200/JCO.2005.03.3266.

    PubMed 16361630
  • Schroth W, Antoniadou L, Fritz P, Schwab M, Muerdter T, Zanger UM, Simon W, Eichelbaum M, Brauch H. Breast cancer treatment outcome with adjuvant tamoxifen relative to patient CYP2D6 and CYP2C19 genotypes. J Clin Oncol. 2007 Nov 20;25(33):5187-93. doi: 10.1200/JCO.2007.12.2705.

    PubMed 18024866
  • Thompson AM, Johnson A, Quinlan P, Hillman G, Fontecha M, Bray SE, Purdie CA, Jordan LB, Ferraldeschi R, Latif A, Hadfield KD, Clarke RB, Ashcroft L, Evans DG, Howell A, Nikoloff M, Lawrence J, Newman WG. Comprehensive CYP2D6 genotype and adherence affect outcome in breast cancer patients treated with tamoxifen monotherapy. Breast Cancer Res Treat. 2011 Jan;125(1):279-87. doi: 10.1007/s10549-010-1139-x. Epub 2010 Sep 1.

    PubMed 20809362
  • Margolin S, Lindh JD, Thoren L, Xie H, Koukel L, Dahl ML, Eliasson E. CYP2D6 and adjuvant tamoxifen: possible differences of outcome in pre- and post-menopausal patients. Pharmacogenomics. 2013 Apr;14(6):613-22. doi: 10.2217/pgs.13.47.

    PubMed 23570465
  • Bradford LD. CYP2D6 allele frequency in European Caucasians, Asians, Africans and their descendants. Pharmacogenomics. 2002 Mar;3(2):229-43. doi: 10.1517/14622416.3.2.229.

    PubMed 11972444
  • Sistonen J, Sajantila A, Lao O, Corander J, Barbujani G, Fuselli S. CYP2D6 worldwide genetic variation shows high frequency of altered activity variants and no continental structure. Pharmacogenet Genomics. 2007 Feb;17(2):93-101. doi: 10.1097/01.fpc.0000239974.69464.f2.

    PubMed 17301689

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Exemestane Tablets, ovarian function suppression/ablation and CYP2D6*10 gene test in people with CYP2D6 Polymorphism, run by Cancer Institute and Hospital, Chinese Academy of Medical Sciences at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 31 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Disease free survival (DFS) (time frame: the first breast cancer local/distant recurrence, the new breast cancer of the contralateral breast, second primary cancer and the death caused by any reason in 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03137368, which also lists 20 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Oct 2018; AzTrials last refreshed its copy on 30 Oct 2026.

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