Personalized Chemoradiation for Lung Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: M.D. Anderson Cancer Center
Disqualifiers: Pregnancy, Renal failure, others
No Placebo Group
Approved in 2 Jurisdictions
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.
12345Is 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.
46789What 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.
1011121314Eligibility 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.
+4 more
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.
+4 more
Trial 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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Group I: Standard Treatment Plan (Cohort One)Experimental Treatment7 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 Treatment7 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
M D Anderson Cancer CenterHouston, TX
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Who Is Running the Clinical Trial?
M.D. Anderson Cancer CenterLead Sponsor
National Heart, Lung, and Blood Institute (NHLBI)Collaborator
References
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Novel Genomic-Based Strategies to Personalize Lymph Node Radiation Therapy. [2019]Current standard radiotherapy doses have been derived from empiric methods rather than a scientific framework. Subclinical nodal dosing remains relatively uniform across most disease sites, despite heterogeneity in patient and tumor biology. It is now clear that there are subsets of patients who will benefit from genomically-informed radiotherapy planning, and there are increasing efforts toward prescribing radiation dose to match the radiosensitivity of the tumor. By using novel genomic biomarkers to personalize delivery of radiotherapy, there is an opportunity to improve loco-regional control and cure rates. We survey the current landscape of personalized radiation oncology across commonly treated disease sites.
An instrument dedicated for modelling of pulmonary radiotherapy. [2018]Radiotherapy plays a pivotal role in lung cancer treatment. Selection of patients for new (radio)therapeutic options aiming at improving outcomes requires reliable and validated prediction models. We present the implementation of a prospective platform for evaluation and development of lung radiotherapy (proPED-LUNG) as an instrument enabling multidimensional predictive modelling.
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]We hypothesized that driver mutations in epidermal growth factor receptor (EGFR) are associated with decreased pathologic response to neoadjuvant chemoradiation (NA-ChRT) in locally advanced non-small cell lung cancer (LA-NSCLC).
Patient-Derived Tumoroid for the Prediction of Radiotherapy and Chemotherapy Responses in Non-Small-Cell Lung Cancer. [2023]Radiation therapy and platinum-based chemotherapy are common treatments for lung cancer patients. Several factors are considered for the low overall survival rate of lung cancer, such as the patient's physical state and the complex heterogeneity of the tumor, which leads to resistance to the treatment. Consequently, precision medicines are needed for the patients to improve their survival and their quality of life. Until now, no patient-derived tumoroid model has been reported to predict the efficiency of radiation therapy in non-small-cell lung cancer. Using our patient-derived tumoroid model, we report that this model could be used to evaluate the efficiency of radiation therapy and cisplatin-based chemotherapy in non-small-cell lung cancer. In addition, these results can be correlated to clinical outcomes of patients, indicating that this patient-derived tumoroid model can predict the response to radiotherapy and chemotherapy in non-small-cell lung cancer.
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Phase I Trial of Definitive Concurrent Chemoradiotherapy and Trametinib for KRAS-Mutated Non-Small Cell Lung Cancer. [2023]This phase I trial (NCT01912625) evaluated the safety and pharmacokinetics of definitive concurrent chemoradiotherapy (cCRT) and the radiosensitizer trametinib (MEK1/2 inhibitor) for KRAS-mutated nonmetastatic non-small cell lung cancer (NSCLC).
Integrative Pharmacogenomics Analysis of Patient-Derived Xenografts. [2019]Identifying robust biomarkers of drug response constitutes a key challenge in precision medicine. Patient-derived tumor xenografts (PDX) have emerged as reliable preclinical models that more accurately recapitulate tumor response to chemo- and targeted therapies. However, the lack of computational tools makes it difficult to analyze high-throughput molecular and pharmacologic profiles of PDX. We have developed Xenograft Visualization & Analysis (Xeva), an open-source software package for in vivo pharmacogenomic datasets that allows for quantification of variability in gene expression and pathway activity across PDX passages. We found that only a few genes and pathways exhibited passage-specific alterations and were therefore not suitable for biomarker discovery. Using the largest PDX pharmacogenomic dataset to date, we identified 87 pathways that are significantly associated with response to 51 drugs (FDR < 0.05). We found novel biomarkers based on gene expressions, copy number aberrations, and mutations predictive of drug response (concordance index > 0.60; FDR < 0.05). Our study demonstrates that Xeva provides a flexible platform for integrative analysis of preclinical in vivo pharmacogenomics data to identify biomarkers predictive of drug response, representing a major step forward in precision oncology. SIGNIFICANCE: A computational platform for PDX data analysis reveals consistent gene and pathway activity across passages and confirms drug response prediction biomarkers in PDX.See related commentary by Meehan, p. 4324.
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Integrative oncology drug discovery accompanied by preclinical translational research as prerequisite for clinical development. [2015]The molecular heterogeneity of cancer calls for individualized therapies to become the standard of care. It is now generally accepted that target-specific compounds require specific new development programs. But, even for new drugs with general mode of action (i.e., chemotherapy), tailored treatment approaches, such as specific schedules or combinations, have been shown to improve the therapeutic outcome. Therefore, the preclinical development of new therapeutic agents needs, next to the "classical pharmacodynamic studies", the implementation of integrative translational research (TR) as early as possible. New TR approaches, starting already at target identification and validation (TIV) will allow to defining the optimal patient population for clinical development, to tailor individual treatment of the tumor disease and to choose a rational basis among the manifold options for treatment combinations. We will discuss several examples from TR studies, which have initially been started to evaluate the molecular mode of action and to recognize mechanisms which can lead to resistance. Research was extended later to identify predictive response biomarkers and establish a rationale for combination with different therapies. A detailed gene expression analysis of lung cancer cells and apoptotic pathway interference studies in colon cancer cells provided insight in the molecular mechanisms of action. These new findings are correlated with results from other studies performed during the preclinical development program. We discuss pros and cons, successes and failures of our integrative preclinical development program and provide recommendations for future oncology projects.
Establishment of a platform of non-small-cell lung cancer patient-derived xenografts with clinical and genomic annotation. [2019]Preclinical models that can better predict therapeutic activity in clinical trials are needed in this era of personalized cancer treatment. Herein, we established genomically and clinically annotated patient-derived xenografts (PDXs) from non-small-cell lung cancer (NSCLC) patients and investigated whether these PDXs would faithfully recapitulate patient responses to targeted therapy.