Trial of Perioperative Endocrine Therapy - Individualising Care (POETIC)

• ClinicalTrials.gov Identifier: NCT02338310
• Recruitment Status: Active, not recruiting
• First Posted: January 14, 2015
• Last Update Posted: February 17, 2020
• Sponsor: Institute of Cancer Research, United Kingdom
• Information provided by (Responsible Party): Institute of Cancer Research, United Kingdom

Tracking Information

• First Submitted Date: September 16, 2014
• First Posted Date: January 14, 2015
• Last Update Posted Date: February 17, 2020
• Study Start Date: September 2008
• Estimated Primary Completion Date: April 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 9, 2015)

Time to recurrence [ Time Frame: 5 years post-randomisation ]

Time to recurrence (TTR) is defined as time from randomisation to local, regional, or distant tumour recurrence or death from breast cancer without prior notification of relapse. Second primary cancers and intercurrent deaths will be treated as censoring events. Patients who are alive and disease free will be censored at the date last seen alive.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 9, 2015)

• Relapse free survival [ Time Frame: 5 years post-randomisation ]
  Second primary cancers and deaths from non-breast cancer causes in the absence of breast cancer relapse will be treated as censoring events.
• Time to local recurrence [ Time Frame: 5 years post-randomisation ]
• Time to distant recurrence [ Time Frame: 5 years post-randomisation ]
• Overall Survival [ Time Frame: 5 years post-randomisation ]
• Breast cancer free survival [ Time Frame: 5 years post-randomisation ]
• Proliferation rate (Ki67) [ Time Frame: At time of surgery (around 2 weeks post-randomisation) ]
  Comparison of the predictive value of Ki67 at surgery in the perioperative therapy and non perioperative therapy groups will be undertaken using Cox regression, comparing the estimates of the hazard ratios obtained in each treatment group.
• Gene expression profile [ Time Frame: At time of surgery (around 2 weeks post-randomisation) ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Trial of Perioperative Endocrine Therapy - Individualising Care
• Official Title: Not Provided

Brief Summary

To determine whether perioperative endocrine therapy with an aromatase inhibitor (AI) followed by standard adjuvant therapy improves outcome compared with standard adjuvant therapy alone in postmenopausal women with hormone receptor positive breast cancer.

To determine whether the proliferation marker Ki67 as measured by immunohistochemistry (IHC) in the excised cancer around 2 weeks after starting AI therapy will predict for time to recurrence (TTR) in the individual patient more effectively than the pre-treatment Ki67 value.

To determine whether molecular profiling 2 weeks after starting endocrine therapy predicts for long-term outcome in postmenopausal women with hormone receptor positive breast cancer better than at diagnosis.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Breast Cancer

Intervention

Drug: Aromatase Inhibitors

Choice of AI is according to centre policy; any brand can be used

Other Names:

• Anastrazole
• Letrozole

Study Arms

• No Intervention: No Aromatase Inhibitor
  No aromatase inhibitor given around the time of surgery
• Experimental: Aromatase Inhibitor
  Aromatase Inhibitor given perioperatively for 4 weeks (two weeks before and two weeks after surgery) Choice of AI is according to centre policy and may be either anastrozole (1mg/day) or letrozole (2.5mg/day)
  Intervention: Drug: Aromatase Inhibitors

• Publications *: Smith I, Robertson J, Kilburn L, Wilcox M, Evans A, Holcombe C, Horgan K, Kirwan C, Mallon E, Sibbering M, Skene A, Vidya R, Cheang M, Banerji J, Morden J, Sidhu K, Dodson A, Bliss JM, Dowsett M. Long-term outcome and prognostic value of Ki67 after perioperative endocrine therapy in postmenopausal women with hormone-sensitive early breast cancer (POETIC): an open-label, multicentre, parallel-group, randomised, phase 3 trial. Lancet Oncol. 2020 Nov;21(11):1443-1454. doi: 10.1016/S1470-2045(20)30458-7. Erratum In: Lancet Oncol. 2020 Dec;21(12):e553.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: January 9, 2015): 4486
• Original Actual Enrollment: Same as current
• Estimated Study Completion Date: April 2034
• Estimated Primary Completion Date: April 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Post menopausal women with core biopsy-proven hormone receptor positive invasive breast cancer. Postmenopausal is defined as a woman aged ≥50 years fulfilling any one of the following criteria:

   i) with amenorrhoea >12 months and an intact uterus; ii) has undergone a bilateral oophorectomy; iii) in women who have undergone a hysterectomy, then FSH levels within the postmenopausal range (utilising ranges from the testing laboratory facility) are required if the patient is aged <55 years; or iv) in women who have been on HRT within the last 12 months and therefore not amenorrhoeic, FSH levels within the postmenopausal range (utilising ranges from the testing laboratory facility) are required if the patient is aged <55 years.

2. No evidence of metastatic spread by standard assessment according to local guidelines
3. Standard adjuvant endocrine therapy indicated
4. A palpable tumour of any size , or a tumour with an ultrasound size of at least 1.5cm
5. WHO performance status of 0 or 1
6. Written informed consent to participate in the trial and to donation of tissue (fresh tissue and surplus tissue from diagnostic procedures) and blood samples.

Exclusion Criteria:

1. Locally advanced/inoperable breast cancer
2. Evidence of metastatic disease
3. Previous invasive breast cancer (surgically treated DCIS or LCIS allowed)
4. Current bilateral breast cancer
5. Multiple unilateral tumours with different ER/PgR/HER2 status, grade or type (e.g. ductal vs lobular) i.e. anything that suggests two or more different cancers. Multifocal disease with homogenous ER/PgR/HER2 status, grade and type is allowed if at least one lesion is palpable or at least 1.5cm on ultrasound; the largest lesion should be used for sample collection and CRF completion.
6. Concurrent use (defined as use within 4 weeks prior to diagnostic tissue sample being taken) of HRT or any other oestrogen-containing medication (including vaginal oestrogens)
7. Previous use of oestrogen implants at ANY time
8. Prior endocrine therapy or chemotherapy for breast cancer
9. Any invasive malignancy diagnosed within previous 5 years (other than basal cell carcinoma or cervical carcinoma in situ)
10. Any severe co-incident medical disease, inability to give informed consent or unavailability for follow-up
11. Treatment with an unlicensed or investigational drug within 4 weeks before randomisation
12. Current, continuous, long term systemic steroid usage

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 50 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT02338310
• Other Study ID Numbers: ICR-CTSU/2007/10015; 2007-003877-21 ( EudraCT Number ); CRUK/07/015 ( Other Grant/Funding Number: Cancer Research UK ); 08/H1102/37 ( Other Identifier: Main Research Ethics Committee Number ); 63882543 ( Registry Identifier: ISRCTN ); CCR 2973 ( Other Identifier: Sponsor )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Institute of Cancer Research, United Kingdom
• Original Responsible Party: Same as current
• Current Study Sponsor: Institute of Cancer Research, United Kingdom
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Ian Smith, Professor; Royal Marsden NHS Foundation Trust

• PRS Account: Institute of Cancer Research, United Kingdom
• Verification Date: February 2020