Radiation + Immunotherapy + Chemotherapy for Lung Cancer

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

26 Participants Needed

Trial Summary

What is the purpose of this trial?

Building upon the clinical experience of the investigators with the magnetic resonance (MR)-guided radiation therapy system and applying principals of hypofractionation toward the current treatment paradigm of concurrent chemoradiation and consolidation immunotherapy for locally advanced non-small cell lung cancer (NSCLC), this prospective, single-arm Phase II clinical trial with safety lead-in will test the feasibility and outcomes of this approach.

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.

What data supports the effectiveness of the treatment Radiation + Immunotherapy + Chemotherapy for Lung Cancer?

Research shows that combining chemotherapy drugs like paclitaxel and carboplatin with radiation therapy can improve local control and potentially increase survival in patients with advanced non-small cell lung cancer. This combination is considered more effective than radiation alone, offering a relatively safe and active regimen for controlling the disease. ^{1 2 3 4 5}

Is the combination of paclitaxel, carboplatin, and radiation therapy safe for treating lung cancer?

The combination of paclitaxel, carboplatin, and radiation therapy has been generally well-tolerated in clinical trials for lung cancer, with manageable side effects like esophagitis (inflammation of the esophagus) and mild myelotoxicity (bone marrow suppression). ^{1 2 6 7 8}

How is the treatment of radiation, immunotherapy, and chemotherapy for lung cancer different from other treatments?

This treatment combines radiation with chemotherapy drugs paclitaxel and carboplatin, which work together to enhance the effectiveness of radiation by making cancer cells more sensitive to it. This approach aims to improve local control and survival rates compared to using radiation or chemotherapy alone. ^{1 2 3 9 10}

Research Team

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

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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 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]

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]

References

1. China 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]. [2010]

2. United States pubmed.ncbi.nlm.nih.gov

Concurrent paclitaxel, carboplatin, and radiation therapy for locally advanced non-small cell lung cancer. [2015]

3. United States pubmed.ncbi.nlm.nih.gov

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

4. United States pubmed.ncbi.nlm.nih.gov

Chemoradiotherapy in non-small cell lung cancer: paclitaxel/carboplatin/radiotherapy in regionally advanced disease. [2015]

5. England 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. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

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

7. United States pubmed.ncbi.nlm.nih.gov

Paclitaxel, carboplatin and radiation therapy for non-small-cell lung cancer. [2015]

8. United States 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. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Multiinstitutional phase II trial of paclitaxel, carboplatin, and concurrent radiation therapy for locally advanced non-small-cell lung cancer. [2017]

10. United States pubmed.ncbi.nlm.nih.gov

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