Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Digestive System Diseases

Rare Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Small Cell Lung Carcinoma

Esophagitis

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Small Cell Lung Cancer

Acute Graft Versus Host Disease

IMRT with CEST and concurrent chemotherapy (any standard-of-care regimen)

Determine whether CEST decreases rate of severe acute esophagitis

Contralateral Esophageal Sparing Technique (CEST)

Henning Willers, MD

This research study is examining the benefit of a novel radiation planning approach on the likelihood of developing severe esophagitis (irritation and inflammation of the esophagus) during the course of radiation therapy with concurrent chemotherapy which is associated with very painful and difficult swallowing.

This research study is a Phase I clinical trial, which tests the safety of an investigational intervention and also tries to define the appropriate dose of the investigational intervention to use for further studies. "Investigational" means that the intervention is being studied.

The U.S. Food and Drug Administration (FDA) has approved radiation with chemotherapy as a treatment option for your disease.

Currently, there are no established rules to avoid esophagitis in the treatment of lung cancer with radiation therapy. We have developed an IMRT-based technique, termed CEST, to reduce the radiation dose to the part of the esophagus that is located opposite to the tumor. The reason behind this approach is that a lower radiation dose causes less esophagus inflammation and irritation and, therefore, may preserve the swallowing function of the esophagus better. In our clinical experience, reducing the radiation dose to part of the esophagus in this fashion has shown the potential to dramatically decrease the likelihood of severe esophagitis in many though not all people with lung cancer. We therefore wish to analyze this technique further.

There is no firm data to indicate that different chemotherapy regimens given at the same time of radiation therapy result in different rates of esophagitis. The Investigators will, therefore, allow any type of standard-of-care chemotherapy regimen at the discretion of the patient's medical oncologist.

Phase I Trial Of IMRT Using A Contralateral Esophagus Sparing Technique (CEST) In Locally Advanced Lung Cancer

A Phase I Trial Of Intensity-Modulated Radiation Therapy (IMRT) Using A Contralateral Esophagus Sparing Technique (CEST) In Locally Advanced Non-Small Cell Lung Cancer (NSCLC) And Limited-Stage Small Cell Lung Cancer (LS-SCLC).

Esophagitis will be measured using the Common Toxicity Criteria for Adverse Effects (CTCAE) v4 scoring scale

Esophagitis will be measured using the historical Radiation Therapy Oncology Group (RTOG) scoring scale

Adverse events will be measured using CTCAE v4 scoring scale

Response and progression will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline. No isolated locoregional tumor failures at a median follow-up of up to 2 years.

Follow-up time will be calculated from the date of registration to the date of death or the last follow-up date on which the patient was reported alive. Overall survival rates will be estimated using the Kaplan-Meier method.

Massachusetts General Hospital

Principal Investigator

Serious adverse events were defined as adverse events with a grade of 3 or higher that were deemed to be possibly, probably, or definitely related to treatment.

IMRT with CEST and concurrent chemotherapy (any standard-of-care regimen)

Contralateral Esophageal Sparing Technique (CEST): Determine whether CEST decreases rate of severe acute esophagitis

Contralateral Esophagus Sparing Technique (CEST)

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

This protocol received IRB approval on 7/20/21 to remove secondary outcome "Median Survival Time" so this pre-specified outcome was subsequently deleted from the CT.gov record. The reason is that the secondary outcome of median survival time was not reached at time of analysis and final publication.

Dr. Henning Willers

Number of Participants With Grade 3 or Higher Acute Esophagitis (CTCAE)

Number of Participants With Grade 3 or Higher Acute Esophagitis (RTOG)

Number of Participants With Adverse Events

Rate of Local and Regional Failure

Overall Survival Rate

Overall Study

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Dermatologic Agents

Etoposide

Carboplatin

Pembrolizumab

Cisplatin

Etoposide phosphate

Podophyllotoxin

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Enzyme Inhibitors

Keratolytic Agents

Tubulin Modulators

Antimitotic Agents

Patients receive pembrolizumab IV over 30 minutes on day 1 and undergo radiation therapy BID 5 days a week for 3 weeks. Patients also receive cisplatin IV over 2 hours or carboplatin IV over 30 minutes and etoposide IV over 4 hours on days 1, 2, and 3. Treatment repeats every 3 weeks for 16 courses (1 course for radiation therapy, 4 courses for chemotherapy) in the absence of disease progression or unacceptable toxicity. Patients who achieve systemic disease control and do not exhibit severe (grade \> 3) pembrolizumab related toxicity during/after completion of 16 courses may receive 16 additional courses of pembrolizumab in the absence of disease progression or unacceptable toxicity.

Beginning after the completion of chemotherapy, patients receive pembrolizumab IV over 30 minutes on day 1 and undergo radiation therapy BID 5 days a week for 3 weeks. Treatment repeats every 3 weeks for 16 courses (1 course for radiation therapy) in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis

Radiation Therapy

James Welsh

This phase I trial studies the side effects and best dose of pembrolizumab when given together with chemoradiotherapy or radiation therapy in treating patients with small cell lung cancer. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill cancer cells and shrink tumors. Giving chemotherapy with radiation therapy may kill more cancer cells. Giving pembrolizumab with chemoradiotherapy or radiation therapy may be a better treatment for small cell lung cancer.

PRIMARY OBJECTIVES:

I. Safety of pembrolizumab (MK 3475) plus chemotherapy (chemo)/radiation for limited-stage small-cell lung cancer (LS-SCLC).

II. Safety of MK-3475 plus radiation for extensive-stage small-cell lung cancer (ES-SCLC).

SECONDARY OBJECTIVES:

I. MK-3475 will improve progression free survival (PFS) compared to historical controls for LS-SCLC and ES-SCLC.

OUTLINE: This is a dose-escalation study of pembrolizumab. Patients are assigned to either Part A or Part B based on diagnosis.

PART A (LS-SCLC): Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and undergo radiation therapy twice daily (BID) 5 days a week for 3 weeks. Patients also receive cisplatin IV over 2 hours or carboplatin IV over 30 minutes and etoposide IV over 4 hours on days 1, 2, and 3. Treatment repeats every 3 weeks for 16 courses (1 course for radiation therapy, 4 courses for chemotherapy) in the absence of disease progression or unacceptable toxicity. Patients who achieve systemic disease control and do not exhibit severe (grade \> 3) pembrolizumab related toxicity during/after completion of 16 courses may receive 16 additional courses of pembrolizumab in the absence of disease progression or unacceptable toxicity.

PART B (ES-SCLC): Beginning after the completion of chemotherapy, patients receive pembrolizumab IV over 30 minutes on day 1 and undergo radiation therapy BID 5 days a week for 3 weeks. Treatment repeats every 3 weeks for 16 courses (1 course for radiation therapy) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, all patients are followed up at 30 days and then every 12 weeks.

Pembrolizumab and Concurrent Chemoradiotherapy or Radiation Therapy in Treating Patients With Small Cell Lung Cancer

Phase I Trial of MK-3475 and Concurrent Chemo/Radiation for the Elimination of Small Cell Lung Cancer

Frequency of adverse events will be tabulated by grade, type, and dose/cohort. Relative frequencies and confidence intervals will also be constructed.

Will be performed using Global Immune Related Response Criteria that factors all indexed and non-indexed lesions, In-Field Immune Related Response Criteria in which only non-radiation therapy-treated lesions and non-index lesions arising outside the radiation therapy planning target volume will be considered, and Out-Field Immune Related Response Criteria in which only non-radiation therapy-treated lesions and non-index lesions arising outside the radiation therapy planning target volume will be considered.

Time to event distributions for progression free survival will be estimated via Kaplan-Meier analysis.

Time to event distributions for overall response will be estimated via Kaplan-Meier analysis.

Descriptive analysis will include a global assessment of patient outcomes for parts A and B separately.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Patients undergo PCI using 3DCRT daily for 2 weeks.

Patients undergo PCI with HA using IMRT daily for 2 weeks.

3-Dimensional Conformal Radiation Therapy

Cognitive Assessment

Intensity-Modulated Radiation Therapy

Quality-of-Life Assessment

Vinai Gondi

This randomized phase II/III trial studies how well whole-brain radiation therapy works and compares it with or without hippocampal avoidance in treating patients with small cell lung cancer that is found in one lung, the tissues between the lungs, and nearby lymph nodes only (limited stage) or has spread outside of the lung in which it began or to other parts of the body (extensive stage). Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. The hippocampus is part of the brain that is important for memory. Avoiding the hippocampus during whole-brain radiation could decrease the chance of side effects on memory and thinking. It is not yet known whether giving whole-brain radiation therapy is more effective with or without hippocampal avoidance in treating patients with small cell lung cancer.

PRIMARY OBJECTIVES:

I. Determine whether the 12-month intracranial relapse rate following hippocampal avoidance (HA)-prophylactic cranial irradiation (PCI) is non-inferior compared to the rate following PCI for patients with small cell lung cancer (SCLC). (Randomized Phase II Component \[Non-Inferiority\]) II. Determine whether HA-PCI reduces the likelihood of 6-month deterioration from baseline in Hopkins Verbal Learning Test (HVLT)-Revised (R) delayed recall compared to PCI for patients with SCLC. (Phase III Component \[Efficacy\])

SECONDARY OBJECTIVES:

I. Compare time to cognitive failure, as measured by a battery of tests (HVLT-R, Controlled Oral Word Association \[COWA\] test, and Trail Making Test \[TMT\] parts A and B), after PCI versus HA-PCI in SCLC.

II. Compare time to cognitive failure as separately measured by each test (HVLT-R for Total Recall and Delayed Recognition, COWA test, and TMT parts A and B), after PCI versus HA-PCI for SCLC.

III. Compare patient-reported cognitive functioning and other quality of life domains (assessed by the European Organization for Research and Treatment of Cancer \[EORTC\] Quality of Life Questionnaire \[QLQ\]-Core \[C\]30 and BN20) between PCI versus HA-PCI for patients with SCLC.

IV. Compare overall survival after PCI versus HA-PCI for patients with SCLC. V. Compare 12-month intracranial relapse rate (at completion of phase III) and time to intracranial relapse after PCI versus HA-PCI for patients with SCLC.

VI. Evaluate adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) criteria.

VII. Correlate changes in health-related quality of life (HRQOL) domains with changes in cognitive testing outcomes following PCI versus HA-PCI for patients with SCLC.

VIII. Assess cost-effectiveness of HA-PCI (intensity modulated radiation therapy \[IMRT\]) and PCI (3-dimensional conformal radiation therapy \[3DCRT\]) using the EuroQual (EQ)-5-Dimensions (5D)-5L.

IX. Correlate miRNA signatures with cognitive failure in SCLC patients who received PCI and HA-PCI.

X. Evaluate APOE genotyping as potential predictor of neurocognitive decline, hippocampal atrophy after brain irradiation and/or differential benefit from hippocampal avoidance.

XI. Evaluate baseline MR imaging biomarkers of white matter injury and hippocampal volumetry as potential predictors of cognitive decline and differential benefit from HA-PCI as compared to PCI.

TERTIARY OBJECTIVES:

I. Collect serum, whole blood, and urine for future translational research analyses.

II. Evaluate baseline magnetic resonance (MR) imaging biomarkers of white matter injury and hippocampal volumetry as potential predictors of cognitive decline and differential benefit from HAPCI as compared to PCI.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients undergo PCI using 3DCRT daily for 2 weeks.

ARM II: Patients undergo PCI with HA using IMRT daily for 2 weeks.

After completion of study treatment, patients are followed every 3 months for 1 year, then every 6 months until 3 years and then annually until death.

Whole-Brain Radiation Therapy With or Without Hippocampal Avoidance in Treating Patients With Limited Stage or Extensive Stage Small Cell Lung Cancer

Randomized Phase II/III Trial of Prophylactic Cranial Irradiation With or Without Hippocampal Avoidance for Small Cell Lung Cancer

The change from baseline to 6 months will be compared between arms using the t-test (or Wilcoxon test if not normally distributed) in the total score and the two subscale scores (agency and pathway). These scores will be correlated with the EORTC- QLQ-C30 total score using a Pearson correlation coefficient. A general linear model will be used to assess hopefulness, performed separately for the AHS total score and subscale scores, between treatment arms while adjusting for depression.

Compared using Fisher's exact test at a significance level of 0.05.

It will be compared between arms using a binomial test of difference in proportions at a significance level of 0.1. If the rate of relapse in the HA-PCI arm is significantly greater than that of the PCI only arm, this study will not continue to the phase III portion.

Quality-adjusted life years (QALY's) will be assessed as the area under the preference-weighted survival curve. Cost will be assessed using a societal perspective. The primary cost-effectiveness outcome will be the pooled incremental cost-per QALY ratio for HA-PCI versus standard PCI. The incremental cost per QALY ratio will be calculated as the total cost of the HA-PCI minus total cost of standard PCI which will be divided by the quality adjusted survival of the patients treated with HA-PCI minus the quality adjusted survival of patients receiving standard PCI.

Counts of all AEs by grade will be provided by treatment arm. Counts and frequencies will be provided for the worst grade AE experienced by the patient by treatment arm.

The occurrence of intracranial relapse will be defined as appearance of brain metastasis in brain. Cumulative incidence approach will be used to estimate the median time to intracranial relapse to account for the competing risk of death. Gray's test will be used to test for statistically significant difference in the distribution of intracranial relapse times. Cause-specific Cox proportional hazards regression model will be used to evaluate effect of stratification variables (age, stage, and planned concurrent memantine use) and other baseline characteristics, on time to intracranial relapse.

Estimated using the Kaplan-Meier method and differences between treatment arms will be tested using the log rank test. The Cox proportional hazard model will be performed with the stratification variables and other baseline characteristics as fixed variables to assess the treatment effect while adjusting for patient-specific risk factors.

Correlation of changes in HRQOL domains measured by the EORTC QLQ-C30 and BN20 with changes in cognitive function will be assessed. Additionally cognitive function decline at 3, 6, 12, 18 and 24 months will also be assessed and compared using Fisher's exact test. Decline from baseline to each time point (3, 6, 12, 18, and 24 months from the start of treatment) in the following subscales will also be assessed and compared using Fisher's exact test: global QOL, physical functioning, role functioning, emotional functioning, and social functioning domains along with fatigue and pain items.

Standardized scores that adjust for age, education, and gender when necessary will be analyzed. For discrete time point analyses, the change from baseline to each follow-up time point (3, 6, 12, 18, and 24 months from the start of treatment) will be calculated and compared between treatment arms using a t-test or Wilcoxon-Mann- Whitney test, depending on the normality of the data. Neurocognitive decline using the RCI for the HVLT-R, COWA, and TMT also will be compared between treatment arms at each follow-up time point using Fisher's exact test.

The cumulative incidence approach will be used to estimate the median time to neurocognitive failure to account for the competing risk of death. Gray's test will be used to test for statistically significant difference in the distribution of neurocognitive failure times. The cause-specific Cox proportional hazards regression model will be used to evaluate the effect of stratification variables (age, stage, and planned concurrent memantine use) and other baseline characteristics, on time to neurocognitive decline.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase I Trial Of IMRT Using A Contralateral Esophagus Sparing Technique (CEST) In Locally Advanced Lung Cancer	NCT02394548	Non-small Cell ... Small Cell Lung...	Contralateral E...	18 Years -	Massachusetts General Hospital
Pembrolizumab and Concurrent Chemoradiotherapy or Radiation Therapy in Treating Patients With Small Cell Lung Cancer	NCT02402920	Extensive Stage... Limited Stage S... Neuroendocrine ...	Carboplatin Cisplatin Etoposide Laboratory Biom... Pembrolizumab Radiation Thera...	18 Years -	M.D. Anderson Cancer Center
Whole-Brain Radiation Therapy With or Without Hippocampal Avoidance in Treating Patients With Limited Stage or Extensive Stage Small Cell Lung Cancer	NCT02635009	Extensive Stage... Limited Stage S...	3-Dimensional C... Cognitive Asses... Intensity-Modul... Laboratory Biom... Quality-of-Life...	18 Years -	NRG Oncology

Spots Global Cancer Trial Database for limited stage small cell lung carcinoma