Immunotherapy + Radiation for Lung Cancer
Recruiting in Palo Alto (17 mi)
Overseen byShahed Badiyan, MD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Waitlist Available
Sponsor: University of Texas Southwestern Medical Center
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This is a randomized Phase II study which is designed to determine the impact of stereotactic radiotherapy and durvalumab on quality-of-life and oncologic outcomes in patients with advanced non-small cell lung cancer. Durvalumab (Imfinzi) and stereotactic radiotherapy, with each fraction of radiotherapy is given every other day on a standard stereotactic ablative radiotherapy (SAbR) schedule or every four weeks on the personalized ultra-fractionated stereotactic adaptive radiotherapy (PULSAR) schedule. Subjects will be followed for a period of 2 years after completion of treatment or until death, whichever occurs first. Specifically, subjects will be followed at 1, 3, 6, 9, 12, 15, 18, 21, and 24 months following treatment. After the 2 year follow up, the patient can continue routine follow up with their physicians, per standard of care. Subjects removed from therapy for unacceptable adverse events will be followed until resolution or stabilization of the adverse event.
Do I need to stop my current medications for the trial?
The trial protocol does not specify if you must stop all current medications. However, you cannot take certain cancer treatments, investigational drugs, or immunosuppressive medications during the trial. It's best to discuss your specific medications with the study team.
What data supports the idea that Immunotherapy + Radiation for Lung Cancer is an effective treatment?
The available research shows that using the drug durvalumab after radiation therapy significantly improves survival in patients with advanced lung cancer. One study highlights that this combination is now a standard treatment because it has shown a significant improvement in survival rates for patients who cannot have surgery. Another study suggests that patients who receive durvalumab after radiation therapy live longer without the cancer spreading compared to those who only receive radiation. This combination is especially beneficial for patients who cannot undergo chemotherapy due to other health issues, as it provides better survival outcomes than radiation alone.
12345What safety data exists for the combination of immunotherapy and radiation in lung cancer treatment?
Safety data for the combination of durvalumab (an anti-PD-L1 therapy) and radiation therapy in lung cancer treatment is available from several studies. A meta-analysis has investigated the safety and efficacy of durvalumab in various solid tumors. A phase 1/2 trial assessed the preliminary safety and efficacy of durvalumab combined with radiotherapy. The DUART trial is specifically assessing the safety and tolerability of durvalumab following radiotherapy in patients with unresectable stage III NSCLC who are ineligible for chemotherapy. These studies provide insights into the safety profile of this treatment combination.
15678Is the drug Durvalumab combined with Stereotactic Radiation Therapy a promising treatment for lung cancer?
Yes, Durvalumab combined with Stereotactic Radiation Therapy is a promising treatment for lung cancer. Studies show that patients treated with Durvalumab had longer survival times and better outcomes compared to those who did not receive it. This combination has been shown to improve the chances of controlling the disease and extending life for patients with certain types of lung cancer.
13569Eligibility Criteria
Adults over 18 with advanced non-small cell lung cancer, who haven't had prior radiation or surgery in the treatment area and have at least one symptomatic metastatic site. They must be able to consent, follow study protocol, have a life expectancy over six months, and use effective birth control. Exclusions include certain medication uses, unresolved toxicities from past therapies, major surgeries within the last month, organ transplants, pregnancy or nursing.Inclusion Criteria
Capable of giving signed informed consent and willing and able to comply with the protocol for the duration of the study
My body weight is over 30 kg.
My cancer was advanced from the start or came back after treatment.
+11 more
Exclusion Criteria
Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
Participation in another clinical study with an investigational product during the last 3 months
I have a history of certain medical conditions or infections.
+19 more
Participant Groups
The trial is testing Durvalumab combined with stereotactic radiotherapy on patients with advanced NSCLC. It aims to see how this affects their quality of life and cancer outcomes. Patients are randomly assigned to receive radiotherapy either every other day (SAbR) or every four weeks (PULSAR), alongside Durvalumab for two years.
2Treatment groups
Experimental Treatment
Active Control
Group I: Personalized Ultra-fractionated Stereotactic Radiotherapy (PULSAR) plus Durvalumab armExperimental Treatment2 Interventions
PULSAR with each radiation treatment fraction delivered every 4 weeks
Group II: Stereotactic Ablative Radiotherapy (SAbR) Arm plus Durvalumab armActive Control2 Interventions
SAbR with each radiation treatment fraction delivered every other day
Durvalumab is already approved in European Union, United States, Japan for the following indications:
🇪🇺 Approved in European Union as Imfinzi for:
- Locally advanced, unresectable non-small cell lung cancer (NSCLC)
🇺🇸 Approved in United States as Imfinzi for:
- Extensive-stage small cell lung cancer (ES-SCLC)
- Limited-stage small cell lung cancer (LS-SCLC)
- Locally advanced or metastatic urothelial carcinoma
🇯🇵 Approved in Japan as Imfinzi for:
- Not specified in provided sources
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Texas Southwestern Medical CenterDallas, TX
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Who Is Running the Clinical Trial?
University of Texas Southwestern Medical CenterLead Sponsor
References
The efficacy profiles of concurrent chemoradiotherapy with intensity-modulated radiotherapy followed by durvalumab in patients with unresectable stage III non-small cell lung cancer: A multicenter retrospective cohort study. [2022]Intensity-modulated radiotherapy (IMRT) is currently used more commonly than 3-dimensional conformal radiation for definitive thoracic radiation. We examined the efficacy profiles of concurrent chemoradiotherapy (CCRT) with IMRT after durvalumab became clinically available.
Nationwide Real-Life Safety and Treatment Exposure Data on Durvalumab After Concurrent Chemoradiotherapy in Unresectable Stage III, Locally Advanced, Non-small Cell Lung Cancer: Analysis of Patients Enrolled in the French Early Access Program. [2022]Consolidation immunotherapy with the PD-L1 inhibitor durvalumab following concurrent chemoradiotherapy (cCRT) has shown a significant survival improvement and is now a standard of care in patients with unresectable stage III or non-operable non-small cell lung cancer (NSCLC).
A comparison of the incidence of ≥ grade 2 radiation pneumonitis between intensity-modulated radiotherapy and three-dimensional conformal radiotherapy in patients with unresectable non-small cell lung cancer treated with durvalumab after concurrent chemoradiotherapy. [2023]Intensity-modulated radiation therapy (IMRT) has been increasingly used as a new radiation modality for unresectable non-small cell lung cancer (NSCLC). The risk factors for radiation pneumonitis (RP) during consolidation durvalumab following concurrent chemoradiotherapy (CCRT) using IMRT have not been thoroughly investigated.
Durvalumab after chemoradiotherapy for locally advanced non-small cell lung cancer prolonged distant metastasis-free survival, progression-free survival and overall survival in clinical practice. [2022]In clinical practice, the effect of durvalumab and radiation pneumonitis (RP) on survival after intensity-modulated radiotherapy (IMRT) is not fully understood. The purpose of this retrospective study was to investigate factors related to distant metastasis-free survival (DMFS), progression-free survival (PFS) and overall survival (OS) after IMRT for locally advanced non-small cell lung cancer (LA-NSCLC).
DUART: durvalumab after radiotherapy in patients with unresectable, stage III NSCLC who are ineligible for chemotherapy. [2022]Consolidation durvalumab is standard of care in patients with unresectable, stage III non-small-cell lung cancer (NSCLC) without disease progression following chemoradiotherapy (the 'PACIFIC regimen'). However, many patients with poor performance status, older age or comorbidities may be ineligible for chemotherapy due to expected high toxicity. These patients typically receive radiotherapy alone, with poor survival outcomes. Based on the PACIFIC trial data, and the strong biological rationale for combining radiotherapy with anti-programmed cell death ligand-1 therapy, durvalumab following radiotherapy could provide additional survival benefit versus radiotherapy alone. Here, we describe the DUART trial, a Phase II, open-label, single-arm study assessing the safety and tolerability of durvalumab following radiotherapy in patients with unresectable, stage III NSCLC who are ineligible for chemotherapy (ClinicalTrials.gov Identifier: NCT04249362).
Concurrent irradiation with the anti-programmed cell death ligand-1 immune checkpoint blocker durvalumab: Single centre subset analysis from a phase 1/2 trial. [2022]To assess preliminary safety and efficacy results of the anti-programmed cell death ligand-1 (anti-PD-L1) durvalumab in combination with radiotherapy (RT) in an expansion cohort of patients included in a phase 1/2 trial at our institution.
Proton and photon radiotherapy in stage III NSCLC: Effects on hematological toxicity and adjuvant immune therapy. [2023]Concurrent chemo-radiotherapy (CCRT) followed by adjuvant durvalumab is standard-of-care for fit patients with unresectable stage III NSCLC. Intensity modulated proton therapy (IMPT) results in different doses to organs than intensity modulated photon therapy (IMRT). We investigated whether IMPT compared to IMRT reduce hematological toxicity and whether it affects durvalumab treatment.
Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. [2022]The prominent immune checkpoint molecule, programmed cell death ligand-1 (PD-L1), is the object of increasing attention. Here, we report a meta-analysis investigating the safety and efficacy of durvalumab (MEDI4736), an inhibitor of PD-L1, in various solid tumors.
Beyond chemoradiotherapy: improving treatment outcomes for patients with stage III unresectable non-small-cell lung cancer through immuno-oncology and durvalumab (Imfinzi®▼, AstraZeneca UK Limited). [2023]The treatment paradigm of non-small-cell lung cancer (NSCLC) has rapidly changed in recent years following the introduction of immune-checkpoint inhibition (ICI). Pre-clinically, both chemotherapy and radiotherapy modulate the tumour microenvironment, providing the rationale for clinical trials evaluating their role in combination with immunotherapy. Standard-of-care treatment for patients with unresectable stage III disease is concurrent chemoradiotherapy (cCRT); however, only recently, the combination with ICI has been explored. The Phase 3 PACIFIC study randomised 713 patients with confirmed locally advanced, unresectable, stage III NSCLC, whose disease has not progressed following cCRT, to either the anti-programmed death-ligand 1 (PD-L1) agent durvalumab (Imfinzi®▼, AstraZeneca UK Limited) or placebo. Patients with a PD-L1 status ≥1% treated with durvalumab had a significantly longer median progression-free survival compared with placebo (17.2 vs. 5.6 months, respectively; HR: 0.51; 95% CI: 0.41-0.63), prolonged median overall survival (OS) (NR vs. 28.7 months, respectively; HR: 0.68; 99.73% CI: 0.47-0.997; P = 0.0025) and long-term clinical benefit (3-year OS HR: 0.69; 95% CI: 0.55-0.86). Grade 3 or 4 toxicity was marginally greater in the durvalumab cohort versus placebo (30.5% vs. 26.1%). Based on these results, durvalumab has been licensed in this setting, and further clinical trials are exploring the use of ICI in unresectable stage III NSCLC.