- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05050929
RAPid SimPLE Targeted Radiation Treatment for Brain Metastases (RAPPLE)
Randomized Phase II Non-Inferiority Study of 5-Day Versus 1-Day RAPid SimPLE (RAPPLE) Targeted Radiation Treatment for Brain Metastases
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Hypothesis For selected patients with limited life expectancy, a single targeted fraction of 8 Gy / 1 to brain metastases will provide equivalent survival as targeted radiotherapy with 20 Gy / 5 to brain metastases.
Justification The QUARTZ study randomized patients with brain metastases and poor prognosis between 20 Gy / 5 whole brain radiotherapy (WBRT) and best supportive care. The median survival in both arms of the study was 9 weeks. The quality of life in both arm was also the same. It is known that WBRT significantly diminishes quality of life. The investigators interpretation of the QUARTZ trial is that the unchecked growth of brain metastases in the best supportive care arm diminishes quality of life as much as WBRT. To control brain metastases without giving WBRT, targeted treatment with 20 Gy / 5 to the metastases alone is standard care at BC Cancer. Numerous randomized trials have compared the efficacy of 20-30 Gy / 5-10 fractions and 8 Gy / 1 for palliative treatment of pain from bone metastases. In addition, there is a randomized trial showing that 20 Gy / 5 and 8 Gy /1 are equally effective for the treatment of symptoms from spinal cord compression. This study will test the use of this shorter, one-visit treatment schedule against the standard 5-visit treatment schedule for patients with brain metastases.
Research Design Randomized Phase II Non-Inferiority Study. The estimated median survival for this cohort, based upon a prior cohort study from 2012-2016 at BC Cancer is 3 months (13 weeks). The investigators would regard a study median survival of less than the 9-week median survival observed in the QUARTZ trial as unacceptable. Hence, the hazard ratio for the experimental arm and the control arm is: 13 weeks / 9 weeks = 1.44. With one-sided Type I error set at alpha = 0.2 and power = 0.8, the investigators calculated a theoretical sample size of 86 patients. Based on prior experience with clinical trials for patients with brain metastases, a 15% risk of drop-out and loss to follow up is expected. Hence the final sample size will be 100 patients. Stratification by the diagnosis-specific graded prognostic assessment (DS-GPA) ranges of 0.0 - 1.0 and 1.5 - 2.0 and lung cancer versus other histologies will help to ensure baseline characteristics that predict for equal survival are equally distributed in both arms of the study.
Statistical Analysis The primary endpoint is overall survival. The study will be considered to be a positive phase II non-inferiority study if the median survival in the experimental arm is within 4 weeks of the median survival in the standard arm.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Sandy Chang
- Phone Number: 2683 604-877-6000
- Email: sandy.chang@bccancer.bc.ca
Study Locations
-
-
British Columbia
-
Abbotsford, British Columbia, Canada
- Recruiting
- BC Cancer - Abbotsford
-
Contact:
- Fred Hsu, BSc MD FRCPC
- Phone Number: 6048514710
-
Kelowna, British Columbia, Canada, V1Y5L3
- Recruiting
- BC Cancer - Kelowna
-
Contact:
- Benjamin Mou, MD FRCPC DABR
- Phone Number: 250-712-3900
- Email: Benjamin.Mou@bccancer.bc.ca
-
Prince George, British Columbia, Canada, V2M7E9
- Recruiting
- BC Cancer - Prince George
-
Contact:
- Robert Olson, MD MSc FRCPC
- Phone Number: 25064573000
- Email: rolson2@bccancer.bc.ca
-
Surrey, British Columbia, Canada
- Not yet recruiting
- BC Cancer - Surrey
-
Contact:
- Sarah Baker, MD
- Phone Number: 604.930.2098
-
Vancouver, British Columbia, Canada, V5Z 4E6
- Recruiting
- BC Cancer - Vancouver
-
Contact:
- Alan Nichol, MD
- Phone Number: 604-877-6046
- Email: anichol@bccancer.bc.ca
-
Principal Investigator:
- Alan Nichol, MD
-
Victoria, British Columbia, Canada
- Recruiting
- BC Cancer - Victoria
-
Contact:
- Isabelle Vallieres, MD MSc FRCPC
- Phone Number: 2505195577
- Email: isabelle.vallieres@bccancer.bc.ca
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
Subjects must meet all of the following criteria to be eligible for participation in this study:
- Age ≥ 18
- Pathological diagnosis of a non-hematopoietic malignancy
- Brain metastases of any size
- Any number of brain metastases that can all be contoured and targeted
- Anticipated median survival insufficient for surgery or stereotactic radiosurgery
- Presence of extracranial disease
- Estimated Glomerular Filtration Rate (eGFR) > 30 ml/min within 90 days
- Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) ≤ 2.0
- Able to complete the EuroQOL (EQ-5D-5L) questionnaire
- Willing and able to have regular imaging follow up
- Feasible to start protocol treatment within 14 days of patient enrolment
- Karnofsky Performance Score (KPS) ≥ 40
- Willing to provide email address on the informed consent form, if unable to attend in-person follow-up assessments
- Signed a consent form prior to enrolment in the trial
Exclusion Criteria:
Subjects are excluded from the study if any of the following criteria apply:
- Inability to have a brain MRI.
- Craniotomy less than 3 months prior to randomization
- Whole brain radiotherapy less than 6 months prior to randomization
- Immunotherapy, targeted therapy or hormone therapy planned after RT
- Disseminated leptomeningeal disease
- Multiple sclerosis
- Neurologically declining despite corticosteroids
- Requiring craniotomy to relieve mass effect
- Systemic lupus erythematosis, scleroderma, or other connective tissue disorders not in remission
- Active alcohol or drug abuse
- History of epilepsy or seizures, and not currently taking anti-epileptic medication
- Any other serious intercurrent illness or medical condition judged by the local investigator to compromise the patient's safety, preclude safe administration of the planned protocol treatment, or prevent the patient from being managed according to the protocol guidelines
- Pregnancy
- Potentially fertile men or women of childbearing potential who are unwilling to employ highly effective contraception
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: 20 Gy in 5 Fractions Volumetric Modulated Arc Therapy to Brain Metastases
Five treatments of 4 Gy will be delivered using volumetric modulated arc therapy on a conventional linear accelerator in a conventional head shell without the use of stereotactic radiosurgery technique.
|
Volumetric Modulated Arc Therapy
|
Experimental: 8 Gy in 1 Fraction Volumetric Modulated Arc Therapy to Brain Metastases
A single treatment of 8 Gy will be delivered using volumetric modulated arc therapy on a conventional linear accelerator in a conventional head shell without the use of stereotactic radiosurgery technique.
|
Volumetric Modulated Arc Therapy
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Survival Time
Time Frame: 1 year
|
The median time from randomization to death
|
1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Median Time to Decline in Karnofsky Performance Status
Time Frame: 1 year
|
The time from randomization to a 20-point decline in Karnofsky Performance Status
|
1 year
|
Control of treated brain metastases
Time Frame: 1 year
|
Cumulative incidence of local recurrence of treated metastases
|
1 year
|
Corticosteroid use
Time Frame: 6 weeks
|
Proportion of patients taking corticosteroids
|
6 weeks
|
Control of brain disease
Time Frame: 1 year
|
Cumulative incidence of (local recurrence of treated metastases OR new metastases)
|
1 year
|
Retreatments for brain metastases
Time Frame: 1 year
|
Proportion of patients with retreatment for brain metastases after radiotherapy
|
1 year
|
Adverse Events
Time Frame: 1 year
|
Cumulative incidence of adverse events, graded using CTCAE Version 5.0
|
1 year
|
Health-Related Quality of Life
Time Frame: 1 year
|
Median time to a minimum clinically important decline in Health-Related Quality of Life
|
1 year
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Alan Nichol, MD, BC Cancer Vancouver
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- H21-01343
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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