Adjuvant Therapy in POLE-Mutated and p53-Wildtype/NSMP Early Stage Endometrial Cancer RAINBO BLUE & TAPER

• ClinicalTrials.gov Identifier: NCT05640999
• Recruitment Status: Recruiting
• First Posted: December 7, 2022
• Last Update Posted: May 2, 2024
• Sponsor: Canadian Cancer Trials Group
• Collaborator: Canadian Cancer Clinical Trials Network
• Information provided by (Responsible Party): Canadian Cancer Trials Group

Tracking Information

• First Submitted Date: November 29, 2022
• First Posted Date: December 7, 2022
• Last Update Posted Date: May 2, 2024
• Actual Study Start Date: December 19, 2022
• Estimated Primary Completion Date: December 31, 2028 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 29, 2022): Estimate the rate of pelvic recurrence at 3 years in patients who are treated with de-escalated adjuvant treatment directed by tumour molecular status [ Time Frame: 3 years ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 20, 2023)

• Estimate the rate of isolated vaginal recurrence at 3 years [ Time Frame: 3 years ]
• Estimate the rate of para-aortic recurrence at 3 years [ Time Frame: 3 years ]
• Estimate the rate of distant metastasis at 3 years [ Time Frame: 3 years ]
• Estimate recurrence-free survival [ Time Frame: 9 years ]
• Estimate endometrial cancer-specific survival [ Time Frame: 9 years ]
• Estimate overall survival [ Time Frame: 9 years ]
• Describe the impact of molecular classification on fear of recurrence by Fear of Recurrence Inventory [ Time Frame: 9 years ]

Original Secondary Outcome Measures (submitted: November 29, 2022)

• Estimate the rate of isolated vaginal recurrence at 3 years [ Time Frame: 3 years ]
• Estimate the rate of para-aortic recurrence at 3 years [ Time Frame: 3 years ]
• Estimate the rate of distant metastasis at 3 years [ Time Frame: 3 years ]
• Estimate recurrence-free survival [ Time Frame: 9 years ]
• Estimate endometrial cancer-specific survival [ Time Frame: 9 years ]
• Estimate overall survival [ Time Frame: 9 years ]
• Describe the impact of molecular classification on patient decisional conflict [ Time Frame: 9 years ]
  Change in level of patient decisional conflict is defined as the change in the Decisional Conflict Scale or subscale prior to and after molecular classification
• Describe the impact of molecular classification on fear of recurrence by Fear of Recurrence Inventory [ Time Frame: 9 years ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Adjuvant Therapy in POLE-Mutated and p53-Wildtype/NSMP Early Stage Endometrial Cancer RAINBO BLUE & TAPER
• Official Title: A Phase II Study of Tailored Adjuvant Therapy in POLE-Mutated and p53-Wildtype/NSMP Early Stage Endormetrial Cancer (RAINBO BLUE & TAPER)

Brief Summary

This protocol tests de-escalated adjuvant treatment in patients with POLE-mutated or p53wt/NSMP (p53 wildtype/no specific molecular profile) early-stage endometrial cancer (EC). Patients may be enrolled in one of two sub-studies

• EN10.A/RAINBO BLUE: POLE-mutated EC
• EN10.B/TAPER: p53 wildtype / NSMP EC

Detailed Description

This study is being done in order to find out if this new approach is better or worse than the usual approach for early-stage endometrial cancer. The usual approach is defined as the care most people get for early-stage endometrial cancer.

The usual approach for patients who are not in a study is treatment with surgery. Tissue that is removed as part of this procedure is analyzed in the pathology laboratory to guide the doctor to decide whether or not additional treatment such as radiation and or chemotherapy should be recommended.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Endometrial Cancer

Intervention

• Radiation: Vaginal brachytherapy
  Vaginal brachytherapy should be delivered using a vaginal cylinder, or alternatively ovoids
• Radiation: Adjuvant radiotherapy (EBRT +/- brachytherapy)
  Treatment is to be delivered using 4-18 MV photons. MV, kV or CBCT imaging capabilities are required. Planning systems with capability for DICOM data transfer must be used.
• Other: Observation
  Observation

Study Arms

• Experimental: Sub-study A: RAINBO BLUE Cohort A1
  Observation
  Intervention: Other: Observation
• Experimental: Sub-Study A: RAINBO BLUE Cohort A2 Exploratory
  Observation or Adjuvant Radiotherapy
  Interventions:

  • Radiation: Adjuvant radiotherapy (EBRT +/- brachytherapy)
  • Other: Observation
• Experimental: Sub-Study B: TAPER
  Observation or Vaginal Brachytherapy
  Interventions:

  • Radiation: Vaginal brachytherapy
  • Other: Observation

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 29, 2022): 325
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 30, 2029
• Estimated Primary Completion Date: December 31, 2028 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patients must have had surgery consisting of hysterectomy and bilateral salpingo-oophorectomy. Lymph node dissection can be performed as per institutional standards. There must be no macroscopic residual disease after surgery.
• Patients must have histologically confirmed Stage I to III endometrial carcinoma which can be endometrioid, serous, clear cell, un/dedifferentiated, carcinosarcoma or mixed.
• Patients' Eastern Cooperative Group (ECOG) performance status must be 0, 1, or 2.
• HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
• Patients' age must be ≥ 18 years.
• Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements.
• Patient is able (i.e. sufficiently fluent) and willing to complete the patient-reported outcomes (PRO) questionnaires in either English, French or a validated language
• Patients must be accessible for treatment and follow-up. Patients enrolled on this trial must be treated and followed at the participating centre
• Protocol treatment is to begin within 10 weeks of hysterectomy/bilateral salpingo-oophorectomy

Exclusion Criteria:

• Prior Neoadjuvant chemotherapy for current endometrial cancer diagnosis.
• Prior pelvic radiation.
• Patients with a history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for ≥ 5 years.
• Clinical evidence of distant metastasis as determined by pre-surgical or post-surgical imaging (CT scan of chest, abdomen and pelvis or whole-body PET-CT scan) (

Sex/Gender

• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Wendy Parulekar; 613-533-6430; wparulekar@ctg.queensu.ca

• Listed Location Countries: Australia, Canada, Netherlands

Administrative Information

• NCT Number: NCT05640999
• Other Study ID Numbers: EN10; NRG-GY032 ( Other Identifier: NRG )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Canadian Cancer Trials Group
• Original Responsible Party: Same as current
• Current Study Sponsor: Canadian Cancer Trials Group
• Original Study Sponsor: Same as current
• Collaborators: Canadian Cancer Clinical Trials Network

Investigators

• Study Chair: Kathy Han; University Health Network, Princess Margaret Hospital, Toronto ON Canada
• Study Chair: Jessica McAlpine; BCCA-Vancouver Cancer Centre, Vancouver BC Canada

• PRS Account: Canadian Cancer Trials Group
• Verification Date: November 2023