Radiation + Immunotherapy + Chemotherapy for Lung Cancer

No longer recruiting at 1 trial location

Overseen By Gregory Vlacich, M.D., Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Washington University School of Medicine

Must not be taking: Oral steroids

Disqualifiers: AIDS, Metastatic cancer, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for individuals with advanced non-small cell lung cancer that cannot be treated with surgery. It uses a mix of radiation therapy, chemotherapy (with carboplatin and paclitaxel), and immunotherapy (with durvalumab) to assess its effectiveness in managing the cancer. Participants must have a confirmed diagnosis of non-small cell lung cancer and be at a stage where radiation and chemotherapy are planned as part of their treatment. The study aims to determine the effectiveness and safety of this combination for patients. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on chronic oral steroids greater than prednisone 10 mg daily, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that combining chemotherapy, radiation, and durvalumab is generally safe for patients with non-small cell lung cancer (NSCLC). In studies where patients received durvalumab after chemotherapy and radiation, serious side effects were uncommon. Only 1.1% of patients experienced life-threatening side effects, and 2.7% had severe reactions. A common issue was pneumonitis, which refers to lung inflammation.

For the chemotherapy drugs carboplatin and paclitaxel, past patients have demonstrated that these can also be safely used with radiation. Side effects like nausea and tiredness may occur, but they are usually manageable.

Overall, this treatment approach appears promising in terms of safety, but individual experiences can vary. Consulting with a healthcare provider can help clarify the potential risks and benefits for those considering participation in such trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment combination for lung cancer because it integrates radiation, chemotherapy, and the immunotherapy drug durvalumab in a potentially powerful way. Unlike traditional treatments that typically use chemoradiation alone, this strategy adds an immune system boost by including durvalumab, which helps the body better recognize and attack cancer cells. Another unique feature is the use of online adaptive radiation planning, which allows for precise adjustments during treatment, potentially increasing effectiveness and reducing side effects. This combination aims to not only target the cancer more effectively but also improve patients’ overall outcomes.

What evidence suggests that this trial's treatments could be effective for lung cancer?

Research has shown that combining chemotherapy and radiation with immunotherapy may help treat locally advanced non-small cell lung cancer (NSCLC). In this trial, participants will receive a combination of the chemotherapy drugs carboplatin and paclitaxel with radiation, which studies have shown can delay cancer growth for an average of 10.5 months. After chemotherapy and radiation, the immunotherapy drug durvalumab will be administered. Specifically, studies have shown that 55.9% of patients who received durvalumab after chemotherapy and radiation remained cancer-free for a year, compared to 35.3% who did not receive it. These findings suggest that this treatment combination could effectively manage NSCLC. ^{6 7 8 9 10}

Who Is on the Research Team?

Gregory Vlacich, M.D., Ph.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for adults with inoperable Stage IIB, IIIA, or select IIIB and IIIC non-small cell lung cancer (NSCLC). Participants may have had previous treatments but no prior thoracic radiation. They must meet certain blood and organ function standards, not be pregnant or breastfeeding, agree to use birth control, and cannot have severe autoimmune diseases or a history of certain lung conditions.

Inclusion Criteria

I have recovered from side effects of previous cancer treatments.

My cancer is at a specific stage and I will be treated with both chemotherapy and radiation.

My cancer is at stage IIIB and I am planning to undergo combined chemotherapy and radiation.

Exclusion Criteria

I have another type of cancer or my cancer has spread.

I have had radiotherapy to my chest area before.

I have had lung conditions like pulmonary fibrosis or pneumonia.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead-in

The first 6 patients are monitored for toxicity related to the experimental chemoradiation

6 months

Chemoradiation

Participants receive concurrent chemoradiation over 3 weeks with 15 fractions of radiation and weekly carboplatin + paclitaxel

3 weeks

Consolidation Immunotherapy

Durvalumab immunotherapy is administered every 2 or 4 weeks for up to 12 months

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin AUC
• Durvalumab
• Paclitaxel
• Radiation therapy
• ViewRay MR-Linear Accelerator

Trial Overview The study tests an advanced form of radiation therapy guided by magnetic resonance imaging (MRI) combined with chemotherapy drugs Carboplatin AUC and Paclitaxel followed by Durvalumab immunotherapy. It's a Phase II trial assessing the safety and effectiveness of this treatment sequence for NSCLC.

How Is the Trial Designed?

Group I: Safety lead-in: Chemoradiation + Durvalumab Experimental Treatment 5 Interventions

* The first 6 patients enrolled on study will comprise the Safety Lead-In cohort and will be closely monitored for toxicity related specifically to the experimental chemoradiation portion of the study treatment. After these 6 patients have been enrolled, accrual will temporarily be suspended for a minimum of 6 months after completion of chemoradiation to allow for the evaluation of adverse events. * Patients will receive concurrent chemoradiation over the course of 3 weeks (15 fractions of radiation with online adaptive treatment planning at fractions 6, 9, and 12 and weekly carboplatin + paclitaxel). Four to 6 weeks after the end of chemoradiation, durvalumab immunotherapy will administered every 2 weeks or 4 weeks (timeline at the discretion of treating physician) for up to 12 months.

Group II: Phase II: Chemoradiation + Durvalumab Experimental Treatment 5 Interventions

-Patients will receive concurrent chemoradiation over the course of 3 weeks (15 fractions of radiation with online adaptive treatment planning at fractions 6, 9, and 12 and weekly carboplatin + paclitaxel). Four to 6 weeks after the end of chemoradiation, durvalumab immunotherapy will administered every 2 weeks or 4 weeks (timeline at the discretion of the treating physician) for up to 12 months.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Published Research Related to This Trial

In a phase III trial involving 200 patients with stage III non-small cell lung cancer, the chemotherapy regimen of etoposide and cisplatin (EP) showed a significantly higher 3-year overall survival rate compared to carboplatin and paclitaxel (PC), with a difference of 15% (P = 0.024).

While EP demonstrated better overall survival, it was associated with a higher incidence of severe esophagitis (20% vs. 6.3% for PC), whereas PC had a higher rate of radiation pneumonitis (33.3% vs. 18.9% for EP), indicating a trade-off in safety profiles between the two regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etoposide and cisplatin versus paclitaxel and carboplatin with concurrent thoracic radiotherapy in unresectable stage III non-small cell lung cancer: a multicenter randomized phase III trial. Liang, J., Bi, N., Wu, S., et al.[2020]

Combined chemotherapy and radiation therapy is more effective than radiation therapy alone for treating unresectable non-small cell lung cancer, although the best timing for chemotherapy (concurrent vs. sequential) is still uncertain.

In patients with stage IIIa and IIIb disease, surgery after neoadjuvant chemotherapy and radiation therapy shows comparable resectability and survival rates, but the impact of surgery on overall survival remains to be established.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current management of unresectable non-small cell lung cancer. Livingston, RB.[2018]

Combined chemotherapy with paclitaxel and carboplatin alongside thoracic radiation therapy has shown a clear survival benefit for patients with locally advanced, unresectable non-small cell lung cancer (NSCLC), as demonstrated in randomized trials and meta-analyses.

Ongoing and planned multicenter studies aim to refine treatment regimens and improve both local and systemic control of NSCLC, highlighting the need for a multidisciplinary approach to effectively manage this systemic disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incorporation of paclitaxel and carboplatin in combined-modality therapy for locally advanced non-small cell lung cancer. Belani, CP.[2015]

A phase II study involving 32 patients with advanced non-small cell lung cancer showed that combining paclitaxel with carboplatin and radiotherapy is feasible and has acceptable toxicity levels, with no grade 4 toxicities reported.

While some patients experienced grade 3 neutropenia and mucositis, the study indicates that this combined treatment approach could improve outcomes, and further research is needed to optimize dosages and treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemoradiotherapy in non-small cell lung cancer: paclitaxel/carboplatin/radiotherapy in regionally advanced disease. Belani, CP., Aisner, J., Bahri, S., et al.[2015]

In a phase II clinical trial involving 40 patients with locally advanced non-small-cell lung cancer (NSCLC), the combination of paclitaxel, carboplatin, and radiation therapy resulted in a high overall response rate of 75.7% and a median overall survival of 20.5 months.

While the treatment was effective, it also led to significant toxicity, with 46% of patients experiencing grade 3 or 4 esophagitis, although late esophageal complications were rare.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiinstitutional phase II trial of paclitaxel, carboplatin, and concurrent radiation therapy for locally advanced non-small-cell lung cancer. Choy, H., Akerley, W., Safran, H., et al.[2017]

Combination therapy using paclitaxel with carboplatin and radiation shows promise as a safer and more effective treatment for non-small cell lung cancer compared to the standard regimen of etoposide and cisplatin.

The use of paclitaxel, a novel taxane drug, in conjunction with radiation therapy may enhance local control of the cancer and improve overall response rates, suggesting a potential advancement in treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent paclitaxel, carboplatin, and radiation therapy for locally advanced non-small cell lung cancer. Choy, H., Akerley, W., DeVore, RF.[2015]

Induction chemotherapy with paclitaxel and carboplatin, followed by concurrent chemoradiation, showed a 55% response rate and a 1-year survival rate of 72% in patients with locally advanced non-small cell lung cancer, indicating promising efficacy.

The treatment regimen was well-tolerated, with mild myelotoxicity as the primary side effect from induction therapy and limited nonhematologic toxicity during concurrent therapy, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent chemoradiation using paclitaxel and carboplatin in locally advanced non-small cell lung cancer. Langer, CJ.[2015]

The combination of paclitaxel and carboplatin followed by thoracic radiation therapy (TRT) has shown promising efficacy in treating locally advanced non-small-cell lung cancer (NSCLC), with a 60% partial response rate to combined therapy and a median survival of 15.3 months for all patients.

The treatment was well-tolerated, with manageable side effects, and the chemotherapy doses were safely escalated, indicating that this approach can be an effective option for patients with locally advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction and concurrent paclitaxel/carboplatin every 3 weeks with thoracic radiotherapy in locally advanced non-small-cell lung cancer: an interim report. Movsas, B., Hudes, RS., Schol, J., et al.[2019]

In a study of 15 patients with inoperable locally advanced non-small cell lung cancer (NSCLC), the combination of paclitaxel, carboplatin, and concurrent radiation therapy resulted in a high overall response rate of 73%, with 13% achieving a complete response and 60% a partial response.

The treatment was associated with manageable toxicity, primarily grade 2 esophagitis in 40% of patients and varying degrees of leukopenia, indicating that while effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A phase I clinical trial of combination chemotherapy of paclitaxel with carboplatin and concurrent radiation therapy in locally advanced non-small cell lung cancer]. Zhu, Y., Zhang, H., Hu, F.[2010]

Citations

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Updated Survival Data for a Phase I/II Study of Carboplatin ... We report the updated survival data for a phase I/II study of carboplatin plus nab‐paclitaxel (nab‐P/C) and concurrent radiotherapy (CRT) in patients with ...

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Efficacy Comparison Between Weekly and Triweekly ... Out of the 104 patients, 52 (50%) patients received weekly carboplatin-paclitaxel (C-P), and 52 (50%) received C-P every 3 weeks. The mean ...

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Phase II trial of paclitaxel, carboplatin, and concurrent ... The median progression-free survival was 10.5 months (95% CI, 7.72–13.28). The major toxicity was hematologic. The incidence of grade 3 esophagitis was 10%. In ...

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3-Weekly Paclitaxel-Carboplatin With Radical Radiation for ... The 1, 3 and 5-year OS rates were 76.9%, 48.3% and 29.7% respectively. ... The maximum grade toxicity was grade 2 in 20 patients (41.5%), grade 3 ...

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NCT03693300 | A Study to Determine Safety of ... This is a Phase II, open-label, multi-centre study to determine the safety of a fixed dose of Durvalumab (MEDI4736) (1500 mg) every 4 weeks [q4w] in ...

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A phase II study of daily carboplatin plus irradiation ... We investigated the clinical benefit of durvalumab after daily carboplatin plus thoracic concurrent radiotherapy.

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AN0025 with Carboplatin, Paclitaxel, Durvalumab and ... Giving AN0025 with carboplatin, paclitaxel durvalumab and radiation may be safe and tolerable in treating patients with stage III NSCLC. Eligibility Criteria ...

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Durvalumab After Chemoradiotherapy in Patients With ... In summary, patients with stage III UR-NSCLC who received durvalumab consolidation after CRT had better outcomes than those who did not receive ...

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IMFINZI® After CRT for unresectable Stage III NSCLC Of the patients who received IMFINZI (475), 1.1% were fatal and 2.7% were Grade 3 adverse reactions. The incidence of pneumonitis (including radiation ...