Dose-escalated Adaptive Radiotherapy of Thoracic Disease for Small Cell Lung Cancer (DARTS): A Prospective Phase II Trial Evaluating Local Control of Adaptive Dose-escalated Radiotherapy
Overview
- Phase
- Phase 2
- Intervention
- Dose-escalated adaptive radiotherapy
- Conditions
- Small Cell Lung Cancer
- Sponsor
- AHS Cancer Control Alberta
- Enrollment
- 31
- Locations
- 1
- Primary Endpoint
- Local failure rate
- Status
- Recruiting
- Last Updated
- 10 months ago
Overview
Brief Summary
The purpose of this study is to find out what effects of using adaptive radiotherapy to deliver chest radiation has on the ability to control lung cancer and side effects.
Detailed Description
This will be an open-label, single-arm, phase II study comparing dose escalated adaptive thoracic radiotherapy to historical control of standard of care single planned radiotherapy field for entire treatment course in patients with newly diagnosed limited stage small cell lung cancer eligible for concurrent chemoradiation with platinum doublet based chemotherapy, or extensive stage small cell lung cancer patients with radiation-targetable intra-thoracic disease and none or limited extra-thoracic disease that are eligible for up-front platinum doublet chemotherapy and are fit to receive concurrent radiotherapy. The adaptive dose-escalated radiotherapy treatment plan will be delivered in three sequential phases with two scheduled replans during the treatment along with scaled dose limits for organs-at-risk. Up to 70 Gy in 35 fractions can be delivered to the disease without overdosing organs-at-risk, and treatment will last 5 - 7 weeks. Scheduled CT simulations for the replans will be at fraction 5 and fraction 10 to account for the expected rapidly shrinking tumour volumes. Participants will be followed for 24 months to investigate local failure rate, medium progression-free survival, overall survival, acute radiation toxicity, and late radiation toxicity. Follow-up after the study will be as per standard-of-care for secondary endpoints.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Minimum 18 years of age
- •Biopsy proven, newly diagnosed, untreated SCLC
- •Completed standard of care staging investigations including: CT chest/abdomen/pelvis, bone scan and/or or PET-CT scan, CT head or MRI brain, or chest X-ray
- •Eligible for platinum doublet chemotherapy
- •Eligible for thoracic radiotherapy, which can also include ipsilateral supraclavicular lymph node disease
- •Capable of providing written, informed consent prior to participation in the study. Patient's legally authorized representative (LAR) may sign on behalf of the patient.
- •Able and willing to comply with protocol rules and follow-up regimen
- •Performance status of ECOG 0-2
- •Pulmonary function tests showing FEV-1 \>1.0L and DLCO \> 50% predicted
- •Radiation-targetable intrathoracic disease
Exclusion Criteria
- •No intrathoracic disease seen to target with radiation
- •Thoracic disease is contiguous to extra-thoracic sites, beyond ipsilateral supraclavicular lymph nodes
- •Mixed histology disease
- •Active serious infection requiring therapy
- •Brain metastasis that has not been symptomatically stable on dexamethasone
- •4 or more sites of extrathoracic disease, even if 2 or more of these are present in the same organ system
- •Previous CNS or thoracic radiotherapy
- •Previous chemotherapy
- •Ineligibility for platinum doublet chemotherapy
- •Life expectancy of less than 3 months
Arms & Interventions
Dose-escalated adaptive chemoradiotherapy
Concurrent with standard of care platinum doublet based chemotherapy (cisplatin + etoposide), radiation treatment plan will be delivered in three sequential phases with two scheduled replans during the treatment along with scaled dose limits for organs-at-risk: Phase 1 dose prescription = 14 Gy in 7 fractions; Phase 2 dose prescription = 10 Gy in 5 fractions starting the day after the final (7th) fraction is delivered; Phase 3 dose prescription = either a) 70 Gy in 35 fractions, or if this cannot be safely reached without exceeding the dose limit of an organ-at-risk, b) the maximum safe prescribe-able dose tolerance specified in the protocol. Either 3D conformal radiotherapy or IMRT planning and delivery techniques will be employed, including contouring relevant thoracic organs-at-risk. All CT simulation scans will be without contrast.
Intervention: Dose-escalated adaptive radiotherapy
Dose-escalated adaptive chemoradiotherapy
Concurrent with standard of care platinum doublet based chemotherapy (cisplatin + etoposide), radiation treatment plan will be delivered in three sequential phases with two scheduled replans during the treatment along with scaled dose limits for organs-at-risk: Phase 1 dose prescription = 14 Gy in 7 fractions; Phase 2 dose prescription = 10 Gy in 5 fractions starting the day after the final (7th) fraction is delivered; Phase 3 dose prescription = either a) 70 Gy in 35 fractions, or if this cannot be safely reached without exceeding the dose limit of an organ-at-risk, b) the maximum safe prescribe-able dose tolerance specified in the protocol. Either 3D conformal radiotherapy or IMRT planning and delivery techniques will be employed, including contouring relevant thoracic organs-at-risk. All CT simulation scans will be without contrast.
Intervention: Chemotherapy
Outcomes
Primary Outcomes
Local failure rate
Time Frame: The local failure rate will be assessed at the time point of 24 months.
The time from diagnostic biopsy to documented progression of intrathoracic disease as assessed by CT or X-ray imaging.
Secondary Outcomes
- Progression-free survival(Median time to PFS in study population. Expected to be within 24 months.)
- Acute radiation toxicity(Expected to be within 3 months.)
- Late radiation toxicity(Late toxicity will be assessed up to 24 months post-treatment.)
- Overall survival(Median time to OS in study population. Expected to be within 24 months.)