Personalized Chemoradiation for Lung Cancer

Overseen By Zhongxing Liao, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Pregnancy, Renal failure, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

100 Participants Needed

Trial Summary

What is the purpose of this trial?

This study assesses cardiovascular injury and cardiac fitness in patients with non-small cell lung cancer that has spread to nearby tissue or lymph nodes (locally advanced) receiving model based personalized chemoradiation. The goal of this study is to learn more about the risk of developing heart disease as a result of chemoradiation treatment for lung cancer. Researchers also want to learn if the risk can be reduced by using a patient's individual risk profile to guide cancer treatment and help protect the heart.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Model Based Personalized Chemoradiation, Tecentriq, MPDL3280A, RG7446 for lung cancer?

Research suggests that personalized radiotherapy, which tailors treatment to the specific characteristics of a patient's tumor, can improve outcomes in lung cancer. Additionally, tools like the Radiotherapy Outcomes Estimator help optimize radiotherapy prescriptions, potentially enhancing the effectiveness of treatments like Model Based Personalized Chemoradiation. ^{1 2 3 4 5}

Is Personalized Chemoradiation for Lung Cancer safe for humans?

The research on similar treatments, like chemoradiotherapy combined with other drugs, shows that they generally have a manageable safety profile, but the specific safety of Personalized Chemoradiation for Lung Cancer would need to be confirmed in its own studies. ^{4 6 7 8 9}

What makes the treatment Model Based Personalized Chemoradiation unique for lung cancer?

This treatment is unique because it combines personalized chemotherapy and radiation therapy, potentially using Tecentriq (an immunotherapy drug) to enhance the effectiveness of radiation by targeting specific molecular pathways in the tumor, which may improve outcomes for patients with hard-to-treat lung cancer. ^{10 11 12 13 14}

Research Team

Zhongxing Liao

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

Adults with locally advanced non-small cell lung cancer who can sign consent, undergo thoracic radiation and systemic therapy (like chemo), and perform cardiac tests. They must have a Karnofsky performance status of 70 or above, indicating they are able to care for themselves. Excluded are those with prior chest radiation, pregnant or breastfeeding women, renal failure patients on dialysis, or anyone unable to do the required heart imaging tests.

Inclusion Criteria

I am willing and able to undergo heart imaging tests.

I am able to care for myself but may not be able to do active work.

I have been diagnosed with non-small cell lung cancer.

Exclusion Criteria

I have had radiation therapy to my chest area before.

I am on dialysis due to kidney failure.

I cannot do the tests required by the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation Therapy (RT)

Participants undergo SPECT/CT with stress test and echocardiogram with strain before RT, and participate in 6 MWT before RT, 2-3 and 6-7 weeks during RT

6-7 weeks

Chemoradiation (CRT)

Participants receive chemoradiation treatment and undergo blood sample collection and complete questionnaires over 3-5 minutes before RT, 2-3, 4-5, 6-7 weeks after the initiation of RT

6-7 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including SPECT/CT with stress test and echocardiogram with strain, 6 MWT, and blood sample collection at 6-8 weeks, 4-6 months, 12 months, and annually up to 10 years

Up to 10 years

Treatment Details

Interventions

• Model Based Personalized Chemoradiation

Trial Overview The trial is studying how personalized chemoradiation treatment affects heart health in lung cancer patients. It involves various cardiac fitness assessments like walking tests and heart scans using techniques such as SPECT and echocardiography before and after treatment to see if tailoring therapy based on individual risk can protect the heart.

Participant Groups

Group I: Standard Treatment Plan (Cohort One) Experimental Treatment 7 Interventions

Patients undergo SPECT/CT with stress test and echocardiogram with strain before RT, 6-8 weeks and 12 months after completion of RT. Patients also participate in 6 MWT before RT, 2-3 and 6-7 weeks during RT, then 6-8 weeks, 4-6 months and 12 months after completion of RT. Patients undergo blood sample collection and complete questionnaires over 3-5 minutes before RT, 2-3, 4-5, 6-7 weeks after the initiation of RT, then at 3, 6, 12, and 24 months after completion of RT.

Group II: Model Based Personalized Treatment Plan (Cohort Two) Experimental Treatment 7 Interventions

Patients undergo SPECT/CT with stress test and echocardiogram with strain before RT, 6-8 weeks and 12 months after completion of RT. Patients also participate in 6 MWT before RT, 2-3 and 6-7 weeks during RT, then 6-8 weeks, 4-6 months and 12 months after completion of RT. Patients undergo blood sample collection and complete questionnaires over 3-5 minutes before RT, 2-3, 4-5, 6-7 weeks after the initiation of RT, then at 3, 6, 12, and 24 months after completion of RT.

Model Based Personalized Chemoradiation is already approved in European Union, United States for the following indications:

Approved in European Union as Tecentriq for:

• Urothelial carcinoma
• Non-small cell lung cancer
• Small cell lung cancer
• Hepatocellular carcinoma
• Alveolar soft part sarcoma

Approved in United States as Tecentriq for:

• Non-small cell lung cancer
• Small cell lung cancer
• Hepatocellular carcinoma
• Melanoma
• Alveolar soft part sarcoma

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Findings from Research

The ROE software tool allows for personalized radiotherapy prescriptions by visualizing tumor control and normal tissue complications based on patient-specific dose-response curves, enhancing treatment planning.

This open-source tool can improve patient understanding of treatment risks and benefits, assess dose escalation potential, and estimate accrual rates for new protocols, making it a valuable resource in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ROE (Radiotherapy Outcomes Estimator): An open-source tool for optimizing radiotherapy prescriptions. Iyer, A., Apte, AP., Bendau, E., et al.[2023]

Current radiotherapy doses are often based on traditional methods rather than scientific evidence, leading to a one-size-fits-all approach that may not suit all patients' needs.

Personalizing radiotherapy using genomic biomarkers can enhance treatment effectiveness by tailoring doses to the specific radiosensitivity of tumors, potentially improving patient outcomes in terms of control and cure rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel Genomic-Based Strategies to Personalize Lymph Node Radiation Therapy. Oliver, DE., Mohammadi, H., Figura, N., et al.[2019]

The proPED-LUNG platform has successfully enrolled 315 lung cancer patients over 18 months, demonstrating high compliance rates (96-100% for patient-rated and 81-94% for physician-rated assessments) for collecting comprehensive data on treatment outcomes and quality of life.

This prospective platform enables multidimensional predictive modeling by gathering extensive baseline and follow-up data, which can help evaluate and improve new radiotherapy options for lung cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An instrument dedicated for modelling of pulmonary radiotherapy. Niezink, AG., Dollekamp, NJ., Elzinga, HJ., et al.[2018]

In a study of 47 patients with locally advanced non-small cell lung cancer (LA-NSCLC) treated with neoadjuvant chemoradiation (NA-ChRT), those with EGFR driver mutations showed significantly lower rates of major pathologic response (MPR) and complete pathologic response (pCR) compared to those without mutations, indicating a reduced effectiveness of treatment.

Patients with EGFR driver mutations also experienced lower local control rates and shorter disease-free survival, suggesting that molecular profiling should be considered for better prognostication and treatment planning in LA-NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of EGFR driver mutations on pathologic regression in resectable locally advanced non-small cell lung cancer treated with neoadjuvant chemoradiation and completion surgery. Appel, S., Bar, J., Saad, A., et al.[2023]

A new patient-derived tumoroid model has been developed to evaluate the effectiveness of radiation therapy and cisplatin-based chemotherapy specifically for non-small-cell lung cancer, addressing the need for precision medicine in treatment.

This model not only assesses treatment responses but also correlates with clinical outcomes, suggesting it could be a valuable tool for predicting how individual patients will respond to these therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-Derived Tumoroid for the Prediction of Radiotherapy and Chemotherapy Responses in Non-Small-Cell Lung Cancer. Nounsi, A., Seitlinger, J., Ponté, C., et al.[2023]

In a study of 26 patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC), the combination of EGFR-TKIs and individualized radiotherapy demonstrated a favorable safety profile, with manageable acute toxicities and severe adverse events occurring in a small percentage of patients.

The treatment resulted in a high local control rate of 96% for thoracic tumors, with median survival time of 21.8 months, indicating that this combination therapy could be an effective option for improving outcomes in NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective study of epidermal growth factor receptor tyrosine kinase inhibitors concurrent with individualized radiotherapy for patients with locally advanced or metastatic non-small-cell lung cancer. Wang, J., Xia, TY., Wang, YJ., et al.[2018]

In a study of 28 patients with locally advanced non-small-cell lung cancer, an intensified chemoradiotherapy (CRT) regimen showed moderate toxicity, with significant Grade 3 or greater leukopenia occurring in 39% of patients during treatment.

The treatment resulted in a locoregional control rate of 52% and an overall survival rate of 31% at 3 years, indicating that this intensified CRT approach is feasible and may be effective for patients ineligible for surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensified high-dose chemoradiotherapy with induction chemotherapy in patients with locally advanced non-small-cell lung cancer-safety and toxicity results within a prospective trial. Pöttgen, C., Eberhardt, WE., Gauler, T., et al.[2018]

The study evaluated the effectiveness of various DNA damage response inhibitors (DDRi) in enhancing the efficacy of radiotherapy in lung cancer cell lines, showing that lower concentrations of these inhibitors can be effective when combined with radiation, particularly in cells with specific genetic deficiencies like p53 mutations.

Among the DDRi tested, AZD0156 was particularly effective at sensitizing p53-deficient cells to radiation, while olaparib, ceralasertib, and adavosertib demonstrated a favorable safety profile, suggesting that careful dose management could optimize treatment outcomes in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiopotentiation Profiling of Multiple Inhibitors of the DNA Damage Response for Early Clinical Development. Gill, SJ., Wijnhoven, PWG., Fok, JHL., et al.[2022]

The maximum tolerated dose (MTD) of trametinib, a MEK1/2 inhibitor, when combined with concurrent chemoradiotherapy (cCRT) for KRAS-mutated non-small cell lung cancer (NSCLC), was determined to be 1.5 mg, indicating a safe dosage for further studies.

Preliminary results showed a median progression-free survival (PFS) of 11 months and overall survival (OS) of 38 months, suggesting that this combination therapy could be effective for patients with this specific cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Trial of Definitive Concurrent Chemoradiotherapy and Trametinib for KRAS-Mutated Non-Small Cell Lung Cancer. Lin, SH., Lin, HY., Verma, V., et al.[2023]

The study developed Xeva, an open-source software that analyzes patient-derived tumor xenografts (PDX) to identify biomarkers predictive of drug response, significantly advancing precision medicine.

Using the largest PDX pharmacogenomic dataset, the researchers identified 87 pathways linked to responses to 51 drugs, revealing novel biomarkers with a high predictive accuracy for drug response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrative Pharmacogenomics Analysis of Patient-Derived Xenografts. Mer, AS., Ba-Alawi, W., Smirnov, P., et al.[2019]

A patient-derived tumor xenograft (PDTX) model for colorectal cancer with liver metastasis was successfully developed, retaining the physiological characteristics of the patient's tumors, which allows for personalized chemotherapy assessments.

The study demonstrated that anticancer drugs like doxorubicin, cisplatin, and docetaxel effectively delayed tumor growth and induced apoptosis in the PDTX model, highlighting its potential for evaluating chemotherapeutic efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Establishing a colorectal cancer liver metastasis patient-derived tumor xenograft model for the evaluation of personalized chemotherapy. Jung, J., Kim, J., Lim, HK., et al.[2022]

The study emphasizes the importance of using 3D cell culture assays to better mimic tumor behavior in vivo, which can improve the prediction of how well targeted therapies will work in actual patients, particularly for head and neck cancers.

By leveraging high-throughput screening of radiation combinations with small-molecule inhibitors across various cancer types, the research aims to identify genomic biomarkers that could enhance the clinical translation of targeted radiosensitizers, potentially leading to more effective treatments for hard-to-treat cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Screening and Validation of Molecular Targeted Radiosensitizers. Willers, H., Pan, X., Borgeaud, N., et al.[2022]

The study emphasizes the need for individualized cancer therapies, highlighting that tailored treatment approaches, including specific schedules and combinations, can enhance the effectiveness of both new and existing drugs.

Integrative translational research (TR) should be implemented early in the development of new therapeutic agents to identify optimal patient populations and mechanisms of resistance, ultimately improving treatment outcomes in cancer care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrative oncology drug discovery accompanied by preclinical translational research as prerequisite for clinical development. Hoffmann, J.[2015]

The study successfully established 41 patient-derived xenografts (PDXs) from 122 non-small-cell lung cancer (NSCLC) patients, demonstrating that these models can accurately reflect patient responses to targeted therapies based on their genomic profiles.

PDXs with specific driver mutations, such as EGFR and ALK alterations, showed similar drug responses to those observed in the corresponding patients, indicating that these PDXs are a valuable tool for personalized cancer treatment and drug discovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Establishment of a platform of non-small-cell lung cancer patient-derived xenografts with clinical and genomic annotation. Kang, HN., Choi, JW., Shim, HS., et al.[2019]

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ROE (Radiotherapy Outcomes Estimator): An open-source tool for optimizing radiotherapy prescriptions. [2023]

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Novel Genomic-Based Strategies to Personalize Lymph Node Radiation Therapy. [2019]

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An instrument dedicated for modelling of pulmonary radiotherapy. [2018]

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Effects of EGFR driver mutations on pathologic regression in resectable locally advanced non-small cell lung cancer treated with neoadjuvant chemoradiation and completion surgery. [2023]

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Patient-Derived Tumoroid for the Prediction of Radiotherapy and Chemotherapy Responses in Non-Small-Cell Lung Cancer. [2023]

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Prospective study of epidermal growth factor receptor tyrosine kinase inhibitors concurrent with individualized radiotherapy for patients with locally advanced or metastatic non-small-cell lung cancer. [2018]

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Intensified high-dose chemoradiotherapy with induction chemotherapy in patients with locally advanced non-small-cell lung cancer-safety and toxicity results within a prospective trial. [2018]

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

Radiopotentiation Profiling of Multiple Inhibitors of the DNA Damage Response for Early Clinical Development. [2022]

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Phase I Trial of Definitive Concurrent Chemoradiotherapy and Trametinib for KRAS-Mutated Non-Small Cell Lung Cancer. [2023]

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Integrative Pharmacogenomics Analysis of Patient-Derived Xenografts. [2019]

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Establishing a colorectal cancer liver metastasis patient-derived tumor xenograft model for the evaluation of personalized chemotherapy. [2022]

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Screening and Validation of Molecular Targeted Radiosensitizers. [2022]

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Integrative oncology drug discovery accompanied by preclinical translational research as prerequisite for clinical development. [2015]

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Establishment of a platform of non-small-cell lung cancer patient-derived xenografts with clinical and genomic annotation. [2019]