MPDL3280A + Chemoradiation for Lung Cancer

Not currently recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Immunostimulants, Immunosuppressants

Disqualifiers: Metastasis, Liver disease, Autoimmune, HIV, 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: 5

Duration: 6-7 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding MPDL3280A (an experimental drug) to standard chemotherapy and radiation is safe and effective for treating non-small cell lung cancer (NSCLC) that cannot be surgically removed and has not spread. Participants will receive a combination of chemotherapy drugs, including Carboplatin and Paclitaxel, along with radiation and MPDL3280A, in various stages to evaluate the effectiveness of this combination. Individuals with non-metastatic, unresectable NSCLC, who have not undergone previous treatments and are willing to try this new approach, may be suitable candidates for the study. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before starting the study. Specifically, you must not have taken any systemic immunostimulatory agents within 6 weeks or systemic immunosuppressive medications within 2 weeks prior to the start of the trial. If you are on these types of medications, you may need to stop them before participating.

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

Research shows that the treatments in this study have been tested for safety in earlier studies. MPDL3280A, also known as atezolizumab, was well-tolerated by patients with non-small cell lung cancer. It can lead to long-lasting improvements and survival benefits, with an acceptable safety profile.

Carboplatin is a common treatment for lung cancer. While some reports mention gaps in safety data, it is generally considered safe for this type of cancer. Paclitaxel, often used with carboplatin, is also considered effective and tolerable. Studies have shown it works well in combination treatments for lung cancer.

Radiation therapy is usually safe for lung cancer patients, though it can cause tiredness and skin changes in the treated area. Combining it with treatments like MPDL3280A has been found to be safe and feasible.

Overall, these treatments are generally well-tolerated, but discussing possible side effects with a doctor is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about MPDL3280A for lung cancer because it represents a new approach compared to standard treatments like chemotherapy and radiation alone. MPDL3280A, also known as atezolizumab, is an immunotherapy drug that works by blocking the PD-L1 protein, which can help the immune system recognize and attack cancer cells more effectively. This mechanism is different from traditional treatments that directly target the cancer cells, offering a potentially more targeted way to enhance the body's own defense mechanisms. Additionally, combining MPDL3280A with chemotherapy and radiation could amplify the overall effectiveness against lung cancer, making it a promising option for patients.

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

Research has shown that atezolizumab, also known as MPDL3280A, holds promise for treating non-small cell lung cancer (NSCLC). Studies have found that patients receiving atezolizumab live longer than those receiving only chemotherapy. This drug aids the immune system in identifying and attacking cancer cells. Some results suggest it is safe and effective, even for patients who have undergone previous treatments. In this trial, one group of participants will receive standard chemotherapy and radiation followed by MPDL3280A, while another group will receive MPDL3280A combined with chemotherapy and radiation from the start. Adding atezolizumab to standard chemotherapy and radiation may enhance the overall effectiveness of lung cancer treatment. ^{6 7 8 9 10}

Who Is on the Research Team?

Steven H. Lin, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with non-small cell lung cancer that can't be removed by surgery and hasn't spread. Participants must have good organ function, agree to use contraception if they can have children, and be willing to follow the study rules. People with severe allergies, certain other cancers or diseases, recent treatments or surgeries, infections like HIV/hepatitis B/C, or who are pregnant/breastfeeding cannot join.

Inclusion Criteria

Ability and willingness to comply with the requirements of the study protocol

For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and/or partner) to use highly effective form(s) of contraception and to continue its use for a specified period after the last dose of MPDL3280A

My blood clotting tests are within normal limits, and I'm not on strong blood thinners.

Exclusion Criteria

I have not had severe infections in the last 4 weeks.

I have a significant liver condition, such as hepatitis or cirrhosis.

I haven't had major surgery in the last 28 days and don't expect to need one during the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive standard chemotherapy and radiation for 6-7 weeks, with MPDL3280A administered weekly

6-7 weeks

Weekly visits for chemotherapy and radiation

Rest Period

Participants have a rest period with no chemotherapy or radiation; Group 2 receives 1 dose of MPDL3280A

3-8 weeks

Consolidation

Participants receive MPDL3280A in addition to chemotherapy for 2 cycles

6 weeks

Visits during Weeks 1-3 and Weeks 4-6

Maintenance

Participants continue to receive MPDL3280A alone for up to 1 year

up to 1 year

Every 2 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 2 years

Every 2-4 months for up to 2 years, then every 4-6 months

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• MPDL3280A
• Paclitaxel
• Radiation Therapy

Trial Overview The trial tests adding MPDL3280A (not yet FDA approved) to standard chemo (carboplatin and paclitaxel) plus radiation therapy in treating lung cancer. The combination's safety is being studied in up to 40 participants at MD Anderson Cancer Center.

How Is the Trial Designed?

Group I: Group 2: MPDL3280A + Chemotherapy + Radiation Experimental Treatment 4 Interventions

Participants receive MPDL3280A, standard chemotherapy, and radiation therapy for 6-7 weeks. This will be followed by a rest period of 3-4 weeks, during which time participant receives 1 dose of MPDL3280A but no chemotherapy or radiation. Consolidation Phase: After the rest period, participants receive MPDL3280A in addition to chemotherapy for 2 cycles. Maintenance Phase: After completing the consolidation period, participants continue to receive MPDL3280A alone for up to 1 year.

Group II: Group 1: Chemotherapy + Radiation Experimental Treatment 4 Interventions

Participants receive standard chemotherapy and radiation for 6-7 weeks, followed by a 3-4 week rest period when they receive no chemotherapy or radiation. Consolidation Phase: After the rest period, participants receive MPDL3280A in addition to chemotherapy for 2 cycles. Maintenance Phase: After completing the consolidation period, participants continue to receive MPDL3280A alone for up to 1 year.

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Published Research Related to This Trial

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]

In a study of 96 lung cancer patients who received thoracic radiotherapy (TRT) after PD-(L)1 inhibitor treatment, nearly 49% developed symptomatic treatment-related pneumonitis, indicating a significant safety concern with this treatment sequence.

Independent risk factors for developing pneumonitis included pulmonary emphysema and lung V20 exposure, highlighting the need for careful patient selection and monitoring when using TRT after PD-(L)1 inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of thoracic radiotherapy after PD-(L)1 inhibitor treatment in patients with lung cancer. Chen, Y., Liu, X., Huang, Z., et al.[2022]

A retrospective study of 40 patients with hilar or mediastinal non-small cell lung cancer (NSCLC) treated with SBRT showed promising results, with a median overall survival of 22.7 months and a two-year local control rate of 87.7%.

The study indicated that SBRT is a safe treatment option, with only a small number of patients experiencing acute or late severe side effects, suggesting that the alternative dose-fractionation schemes used may improve safety without compromising efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation therapy for isolated hilar and mediastinal non-small cell lung cancers. Horne, ZD., Richman, AH., Dohopolski, MJ., et al.[2018]

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]

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 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]

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]

The combination of NBTXR3, high-dose radiation, low-dose radiation, and immune checkpoint inhibitors significantly improved survival rates in a mouse model of anti-PD1-resistant metastatic lung cancer, increasing survival from 0% to 50%.

This treatment enhanced the immune response by increasing CD8 T-cell infiltration and reducing regulatory T cells in the tumors, suggesting that NBTXR3 may help overcome resistance to anti-PD1 therapy by promoting a stronger antitumor immune response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A radioenhancing nanoparticle mediated immunoradiation improves survival and generates long-term antitumor immune memory in an anti-PD1-resistant murine lung cancer model. Hu, Y., Paris, S., Barsoumian, H., et al.[2022]

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