Dose-escalated Adaptive Radiotherapy of Thoracic Disease for Small Cell Lung Cancer (DARTS)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Small Cell Lung Cancer
• Intervention / Treatment: Radiation: Dose-escalated adaptive radiotherapy; Drug: Chemotherapy

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.

• Study Type: Interventional
• Enrollment (Estimated): 31
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yee Don, MD; Phone Number: 780-432-8783; Email: don.yee@ahs.ca

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Recruiting
      • Cross Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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
• Prior thoracic surgery
• History of another primary malignancy other than cutaneous basal cell carcinoma unless disease-free for at least 5 years
• Pregnant or breast-feeding
• In LS-SCLC, patients that are not eligible for concurrent chemoradiotherapy
• In ES-SCLC, patients that are not eligible for concurrent chemoradiotherapy under the experimental arm
• CT contrast allergy or kidney disease with irreversibly low creatinine clearance inadequate for IV contrast administration (for the purposes of high quality contrast enhanced CT chest and abdomen for follow-up imaging)
• Lack of intrathoracic disease or intrathoracic disease spread not feasible to treat with adaptive radiotherapy
• Participant in development and conduct of the research study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Radiation: Dose-escalated adaptive radiotherapy; Adaptive planning of Radiation Therapy with two re-plans of the treatment field through course of therapy with the shrinking treatment fields according to tumor response to escalate dose, as allowed by dose to organs-at-risk.; Drug: Chemotherapy; Concurrent standard of care platinum doublet based therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local failure rate	The time from diagnostic biopsy to documented progression of intrathoracic disease as assessed by CT or X-ray imaging.	The local failure rate will be assessed at the time point of 24 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	Time from diagnostic biopsy to first documented clinical or radiographic evidence of local progression or new metastatic disease.	Median time to PFS in study population. Expected to be within 24 months.
Overall survival	Time from diagnostic biopsy to death of the patient.	Median time to OS in study population. Expected to be within 24 months.
Acute radiation toxicity	Toxicity during and in the 3 months after radiotherapy as defined by CTCAE v.5 for esophagus, skin, lung, heart, and subcutaneous tissue.	Expected to be within 3 months.
Late radiation toxicity	Toxicity seen 3 months after radiotherapy as defined by CTCAE v.5 for esophagus, skin, lung, heart, and subcutaneous tissue.	Late toxicity will be assessed up to 24 months post-treatment.

Collaborators and Investigators

• Sponsor: AHS Cancer Control Alberta
• Investigators: Principal Investigator: Yee Don, MD, Cross Cancer Institute, Alberta Health Services

Study record dates

Study Major Dates

• Study Start (Actual): June 13, 2022
• Primary Completion (Estimated): November 1, 2025
• Study Completion (Estimated): November 1, 2025

Study Registration Dates

• First Submitted: June 28, 2021
• First Submitted That Met QC Criteria: June 28, 2021
• First Posted (Actual): July 7, 2021

Study Record Updates

• Last Update Posted (Actual): January 30, 2024
• Last Update Submitted That Met QC Criteria: January 29, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Small cell lung cancer; (Dose-escalated) Adaptive radiotherapy
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Thoracic Diseases
• Other Study ID Numbers: IIT-0015

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No