Carcinoma, Non-Small-Cell LungNCT02492867
A Pilot Study of Response-Driven Adaptive Radiation Therapy for Patients With Locally Advanced Non-Small Cell Lung Cancer
A study testing Response-driven Adaptive Radiation Therapy, Carboplatin and Paclitaxel in people with Carcinoma, Non-Small-Cell Lung, run by University of Michigan Rogel Cancer Center at 2 sites in United States.
Trial summary
Successful treatment of lung cancer with radiation therapy requires that the physicians determine exactly where the tumor is in the patient's body and seek to limit any unnecessary radiation to normal parts of the body. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Non-Small-Cell Lung
- What is being tested?
- Response-driven Adaptive Radiation Therapy, Carboplatin and Paclitaxel
- Type of treatment
- Injection or infusion, Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 2 sitesUnited States
- Study dates
- 14 Jan 2016to 21 Apr 2022
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have FDG-avid and pathologically proven Stage IIA-IIIB non-small cell lung cancer.
- Patients must be considered unresectable or inoperable.
- Patients must be 18 years of age or older.
- Patients must have a Karnofsky performance (A measure general well-being and activities of daily life. Scores range between 0 and 100 where 100 represents normal and 0 represents death.) of score > or = to 70.
- Patients must have adequate organ and marrow function.
- Patient must be willing to use effective contraception if female with reproductive capability.
- Patients must be informed of the investigational nature of this study and given written informed consent in accordance with institutional and federal guidelines.
Who cannot join
- Patients with any component of small cell lung carcinoma
- Patients with evidence of a malignant pleural or pericardial effusion
- Prior radiotherapy to the thorax such that composite radiation would significantly overdose critical structures, either per estimation of the treating radiation oncologist or defined by failure to meet normal tissue tolerance constraints
- Patients cannot tolerate concurrent chemotherapy
- Pregnant women are excluded from this study because radiation has the potential for teratogenic or abortifacient effects.
- Prisoners are excluded for this study.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
VA Ann Arbor Healthcare System
Ann Arbor, Michigan, 48105
University of Michigan Cancer Center
Ann Arbor, Michigan, 48109
About this study
Successful treatment of lung cancer with radiation therapy requires that the physicians determine exactly where the tumor is in the patient's body and seek to limit any unnecessary radiation to normal parts of the body. This study is designed to apply functional imaging, Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) ("a PET scan") and Ventilation/Perfusion Single Photon Emission Computerized Tomography (V/Q SPECT) ("a perfusion scan"), before treatment and then again during treatment to see if this scanning helps predict how well the treatment works and how well the lung functions during treatment. FDG-PET is a modern technology that uses small amounts of a radioactive glucose (FDG) to make images of the whole body and areas of active cancer. V/Q SPECT is an image mapping tool that helps assess how well the lungs are working. A Computerized Tomography (CT) will also be performed along with both of these procedures to help the researchers see clearly where the cancer or the healthy lung is located.
The researchers are also doing blood and urine tests in this study to look for markers to see if this helps them determine the patient's risk of developing side effects from radiation to the lungs. The researchers hope by using these types of tests that they can have more information to help decrease the amount of toxicity patients have from this type of treatment. The researchers hope that this study will help them in the future to design radiation treatment plans that provide the best treatment for each individual patient.
Read the detailed description
This is a pilot study to improve local tumor control while maintaining the same rate of treatment toxicity by adapting therapy to the uninvolved lung and esophagus while continuing to adapt therapy to the tumor for patients with Stage II/III NSCLC.
Lung cancer is the leading cause of cancer death in the United States and worldwide. In 2012, there were 226,160 new cases and 160,340 deaths related to lung cancer in the United States. Approximately, 80-85% of lung cancers are NSCLC (Non-small Cell Lung Cancer), and 40% of these are locally advanced (stage II/III) at diagnosis. The current standard of care for these patients is "one size fits all" RT (Radiation Therapy) with concurrent chemotherapy in uniform regimens. Even after concurrent chemoradiation, however, the five year overall survival was still about 15%; almost one half of the patients failed locally. At the same time, intensification of both radiotherapy and concurrent chemotherapy may result in excessive toxicity or incomplete treatment. Therefore, it is critical to tailor the treatment to each individual's sensitivity in combination with functional imaging guided response-driven treatment and biomarker guided individualized dose prescription, thus taking into consideration both the tumor and toxicity profile.
Evidence suggests that high-dose radiation has the potential to improve local-regional control and overall survival in patients treated with fractionated therapy with concurrent chemotherapy.
However, it is challenging to deliver high dose RT in the majority of patients with locally advanced NSCLC without exceeding doses to organs at risk and causing significant side effects.
Investigators hypothesized that they could develop safer and more effective therapy by adapting treatment to the individual patient's response. With respect to the tumor, investigators hypothesized, that they could improve outcome by redistributing dose to the more aggressive regions of the tumor, assessed using mid-treatment FDG-PET (Positron Emission Tomography) scanning. With respect to uninvolved organs, investigators need methods of estimating tolerable radiation doses for the individual patient rather than the population average. Such a strategy requires assessing both global and regional normal lung function and the technology to deliver dose in a manner that minimizes damage to functional lung and esophagus.
During-RT FDG-PET/CT potentially can provide important benefits to individual patients by intensifying dose to more resistent tumor, allowing early changes to alternative, more efficacious treatment or by avoiding the unnecessary toxicity related to ineffective therapy.
Patients will also undergo a during treatment V/Q SPECT (Single-photon Emission Computed Tomography) scan, as an adaptive plan based on during-treatment SPECT may further optimize PART (Personalized Adaptive Radiotherapy) to avoid high dose radiation to the well-functioning regions, and would thus decrease RILT (Radiation Induced Lung Toxicity).
The combination of pre- and during V/Q SPECT can classify the lung into different functional regions, and a strategy to give differential priority to the regions has been developed to minimize lung damage.
Investigators plan to continue to collect data on serum biomarkers to further refine their biophysical model with the ultimate goal of individualizing radiation dose prescription.
By identifying high risk patients and adjusting OAR (Organs at Risk) dose limits to the threshold of tolerance, investigators anticipate a significant reduction in the incidence of toxicity from UMCC 2007.123 (NCT01190527) without compromised tumor control by applying the model to optimize radiation planning.
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Being tested
- Response-driven Adaptive Radiation Therapy, Carboplatin, Paclitaxel, FDG-PET, V/Q SPECT
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Response-driven Adaptive Radiation TherapyRadiation
CarboplatinDrug
AUC 2 concurrent with RT; AUC 6 during consolidation. Given IV
PaclitaxelDrug
40 mg/m^2 IV concurrent with RT; 200 mg/m^2 during consolidation. Given IV
FDG-PETDevice
Also called Positron Emission Tomography Scan
V/Q SPECTDevice
Also called Single-photon Emission Computed Tomography Scan
DurvalumabDrug
10 mg/kg during consolidation. Given IV
| Study group | Role | What they receive |
|---|---|---|
| Response-driven Adaptive RT | Experimental | Patients will receive treatment 5 days per week, in once daily fractions, for 30 treatments with dose per fraction individually adapted over the final 9 treatments. Patients may also receive concurrent chemotherapy with Carboplatin and Paclitaxel. Patients may receive consolidation chemotherapy (carboplatin and paclitaxel) or immunotherapy (durvalumab) at the discretion of the medical oncologist. Receives: Radiation: Response-driven Adaptive Radiation Therapy; Drug: Carboplatin; Drug: Paclitaxel; Device: FDG-PET; Device: V/Q SPECT; Drug: Durvalumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Number of Patients for Whom Treatment is Feasible.
To determine the feasibility of the proposed adaptive treatment strategy, we will look at the number of patients for whom treatment is feasible. Treatment is feasible if we are able to deliver the full treatment, using the image based spatial replanning and complete the cytokine assays in a short enough timeframe to adapt radiation dose.
Measured: 6 weeks (30 treatments, 5 days per week)
The Number of Patients That Experience Grade 2 or Greater Lung Toxicity
Lung toxicity will be graded using CTCAE v4.0. These will include, but not be limited to: cough, dyspnea, pneumonitis, radiation pneumonitis, and radiographic or clinical pulmonary fibrosis.
Measured: Up to 24 months
The Number of Patients That Experience Grade 2 or Greater Esophageal Toxicity
Esophageal toxicities will be graded using CTCAE v4.0. These will include, but not be limited to esophagitis.
Measured: Up to 3 months
Comparison of Delivered Dose to Dose That Would Have Been Administered Using the Criteria Described in Protocol UMCC 2007.123 (NCT01190527)
Investigators will generate the treatment plan (and hence dose to PET avid region) each patient would have received if they had been treated on protocol UMCC 2007.123 (NCT01190527), which redistributed dose to the PET avid region but not through normal tissue. These dose values will then be compared to the doses actually given to assess for any mean differences.
Measured: 6 weeks (30 treatments, 5 days per week)
Secondary outcomes (2)
Time to Local Progression
Defined as the time from start of treatment to time of local/regional progression on PET, summarized with the Kaplan-Meier method.
Measured: Up to 60 months
Overall Survival Time
Defined as the time from start of treatment to death.
Measured: Up to 60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2015 (estimated)
- Study start14 Jan 2016
- Primary completion28 Nov 2021
- Study completion21 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Carcinoma, Non-Small-Cell LungStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan Rogel Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Shruti Jolly, M.D., Principal investigator, University of Michigan Rogel Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02492867
- Sponsor's protocol ID
- UMCC 2015.035
- Other IDs
- HUM00098202, P01CA059827
- Status last verified
- Aug 2024
- First submitted
- 30 Jun 2015
- Last updated
- 3 Sep 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Response-Driven Adaptive Radiation Therapy for Patients With Locally Advanced Non-Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT02492867
- Acronym / sponsor ID
- UMCC 2015.035
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- University of Michigan Rogel Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 14 Jan 2016 (actual)
- Primary completion
- 28 Nov 2021 (actual)
- Study completion
- 21 Apr 2022 (actual)
- First posted
- 9 Jul 2015 (estimated)
- Results
- Posted 3 Sep 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Successful treatment of lung cancer with radiation therapy requires that the physicians determine exactly where the tumor is in the patient's body and seek to limit any unnecessary radiation to normal parts of the body. This study is designed to apply functional imaging, Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) ("a PET scan") and Ventilation/Perfusion Single Photon Emission Computerized Tomography (V/Q SPECT) ("a perfusion scan"), before treatment and then again during treatment to see if this scanning helps predict how well the treatment works and how well the lung functions during treatment. FDG-PET is a modern technology that uses small amounts of a radioactive glucose (FDG) to make images of the whole body and areas of active cancer. V/Q SPECT is an image mapping tool that helps assess how well the lungs are working. A Computerized Tomography (CT) will also be performed along with both of these procedures to help the researchers see clearly where the cancer or the healthy lung is located.
The researchers are also doing blood and urine tests in this study to look for markers to see if this helps them determine the patient's risk of developing side effects from radiation to the lungs. The researchers hope by using these types of tests that they can have more information to help decrease the amount of toxicity patients have from this type of treatment. The researchers hope that this study will help them in the future to design radiation treatment plans that provide the best treatment for each individual patient.
Detailed description
This is a pilot study to improve local tumor control while maintaining the same rate of treatment toxicity by adapting therapy to the uninvolved lung and esophagus while continuing to adapt therapy to the tumor for patients with Stage II/III NSCLC.
Lung cancer is the leading cause of cancer death in the United States and worldwide. In 2012, there were 226,160 new cases and 160,340 deaths related to lung cancer in the United States. Approximately, 80-85% of lung cancers are NSCLC (Non-small Cell Lung Cancer), and 40% of these are locally advanced (stage II/III) at diagnosis. The current standard of care for these patients is "one size fits all" RT (Radiation Therapy) with concurrent chemotherapy in uniform regimens. Even after concurrent chemoradiation, however, the five year overall survival was still about 15%; almost one half of the patients failed locally. At the same time, intensification of both radiotherapy and concurrent chemotherapy may result in excessive toxicity or incomplete treatment. Therefore, it is critical to tailor the treatment to each individual's sensitivity in combination with functional imaging guided response-driven treatment and biomarker guided individualized dose prescription, thus taking into consideration both the tumor and toxicity profile.
Evidence suggests that high-dose radiation has the potential to improve local-regional control and overall survival in patients treated with fractionated therapy with concurrent chemotherapy.
However, it is challenging to deliver high dose RT in the majority of patients with locally advanced NSCLC without exceeding doses to organs at risk and causing significant side effects.
Investigators hypothesized that they could develop safer and more effective therapy by adapting treatment to the individual patient's response. With respect to the tumor, investigators hypothesized, that they could improve outcome by redistributing dose to the more aggressive regions of the tumor, assessed using mid-treatment FDG-PET (Positron Emission Tomography) scanning. With respect to uninvolved organs, investigators need methods of estimating tolerable radiation doses for the individual patient rather than the population average. Such a strategy requires assessing both global and regional normal lung function and the technology to deliver dose in a manner that minimizes damage to functional lung and esophagus.
During-RT FDG-PET/CT potentially can provide important benefits to individual patients by intensifying dose to more resistent tumor, allowing early changes to alternative, more efficacious treatment or by avoiding the unnecessary toxicity related to ineffective therapy.
Patients will also undergo a during treatment V/Q SPECT (Single-photon Emission Computed Tomography) scan, as an adaptive plan based on during-treatment SPECT may further optimize PART (Personalized Adaptive Radiotherapy) to avoid high dose radiation to the well-functioning regions, and would thus decrease RILT (Radiation Induced Lung Toxicity).
The combination of pre- and during V/Q SPECT can classify the lung into different functional regions, and a strategy to give differential priority to the regions has been developed to minimize lung damage.
Investigators plan to continue to collect data on serum biomarkers to further refine their biophysical model with the ultimate goal of individualizing radiation dose prescription.
By identifying high risk patients and adjusting OAR (Organs at Risk) dose limits to the threshold of tolerance, investigators anticipate a significant reduction in the incidence of toxicity from UMCC 2007.123 (NCT01190527) without compromised tumor control by applying the model to optimize radiation planning.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Response-driven Adaptive RT | Experimental | Radiation: Response-driven Adaptive Radiation Therapy, Drug: Carboplatin, Drug: Paclitaxel, Device: FDG-PET, Device: V/Q SPECT, Drug: DurvalumabPatients will receive treatment 5 days per week, in once daily fractions, for 30 treatments with dose per fraction individually adapted over the final 9 treatments. Patients may also receive concurrent chemotherapy with Carboplatin and Paclitaxel. Patients may receive consolidation chemotherapy (carboplatin and paclitaxel) or immunotherapy (durvalumab) at the discretion of the medical oncologist. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patients must have FDG-avid and pathologically proven Stage IIA-IIIB non-small cell lung cancer.
- Patients must be considered unresectable or inoperable.
- Patients must be 18 years of age or older.
- Patients must have a Karnofsky performance (A measure general well-being and activities of daily life. Scores range between 0 and 100 where 100 represents normal and 0 represents death.) of score > or = to 70.
- Patients must have adequate organ and marrow function.
Key exclusion criteria (6 listed)
- Patients with any component of small cell lung carcinoma
- Patients with evidence of a malignant pleural or pericardial effusion
- Prior radiotherapy to the thorax such that composite radiation would significantly overdose critical structures, either per estimation of the treating radiation oncologist or defined by failure to meet normal tissue tolerance constraints
- Patients cannot tolerate concurrent chemotherapy
- Pregnant women are excluded from this study because radiation has the potential for teratogenic or abortifacient effects.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Response-driven Adaptive Radiation Therapy | Radiation | Response-driven Adaptive RT |
| CarboplatinAUC 2 concurrent with RT; AUC 6 during consolidation. Given IV | Drug | Response-driven Adaptive RT |
| Paclitaxel40 mg/m^2 IV concurrent with RT; 200 mg/m^2 during consolidation. Given IV | Drug | Response-driven Adaptive RT |
| FDG-PETAlso: Positron Emission Tomography Scan | Device | Response-driven Adaptive RT |
| V/Q SPECTAlso: Single-photon Emission Computed Tomography Scan | Device | Response-driven Adaptive RT |
| Durvalumab10 mg/kg during consolidation. Given IV | Drug | Response-driven Adaptive RT |
Primary outcome
The Number of Patients for Whom Treatment is Feasible.
Time frame: 6 weeks (30 treatments, 5 days per week)
To determine the feasibility of the proposed adaptive treatment strategy, we will look at the number of patients for whom treatment is feasible. Treatment is feasible if we are able to deliver the full treatment, using the image based spatial replanning and complete the cytokine assays in a short enough timeframe to adapt radiation dose.
The Number of Patients That Experience Grade 2 or Greater Lung Toxicity
Time frame: Up to 24 months
Lung toxicity will be graded using CTCAE v4.0. These will include, but not be limited to: cough, dyspnea, pneumonitis, radiation pneumonitis, and radiographic or clinical pulmonary fibrosis.
The Number of Patients That Experience Grade 2 or Greater Esophageal Toxicity
Time frame: Up to 3 months
Esophageal toxicities will be graded using CTCAE v4.0. These will include, but not be limited to esophagitis.
Comparison of Delivered Dose to Dose That Would Have Been Administered Using the Criteria Described in Protocol UMCC 2007.123 (NCT01190527)
Time frame: 6 weeks (30 treatments, 5 days per week)
Investigators will generate the treatment plan (and hence dose to PET avid region) each patient would have received if they had been treated on protocol UMCC 2007.123 (NCT01190527), which redistributed dose to the PET avid region but not through normal tissue. These dose values will then be compared to the doses actually given to assess for any mean differences.
2 secondary outcomes
Time to Local Progression
Time frame: Up to 60 months
Overall Survival Time
Time frame: Up to 60 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Sep 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Carcinoma, Non-Small-Cell Lung
Active, not recruitingPhase 1/2
A Beta-only IL-2 ImmunoTherapY Study
Advanced Solid Tumor, Unresectable Solid Tumor
RecruitingPhase 2/3
Phase 2 Trial of Adagrasib Monotherapy and in Combination With Pembrolizumab and a Phase 3 Trial of Adagrasib in Combination in Patients With a KRAS G12C Mutation KRYSTAL-7
Advanced Non-Small Cell Lung Cancer, Metastatic Non-Small Cell Lung Cancer
RecruitingPhase 3
A Clinical Trial of Adjuvant Intismeran (V940) With or Without Pembrolizumab Coformulated With Berahyaluronidase Alfa (MK-3475A) in High-Risk Stage I Non-Small Cell Lung Cancer (V940-014)
Non-small Cell Lung Cancer
Recruiting
Understanding the Feasibility of a Co-designed Pre-radiotherapy Exercise Programme - A Single-arm Study
Lung Cancer
RecruitingPhase 2
Adjuvant ctDNA-Adapted Personalized Treatment in Early Stage NSCLC (ADAPT-E)
Non-small Cell Lung Cancer, Non-small Cell Lung Cancer Stage I
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shruti Jolly, M.D. principal investigator
University of Michigan Rogel Cancer Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Response-driven Adaptive Radiation Therapy, Carboplatin and Paclitaxel in people with Carcinoma, Non-Small-Cell Lung, run by University of Michigan Rogel Cancer Center at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Number of Patients for Whom Treatment is Feasible. (time frame: 6 weeks (30 treatments, 5 days per week)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Sep 2024.