Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Durvalumab

Tremelimumab

Antineoplastic Agents, Immunological

Drug: Durvalumab Other Names: MEDI4736

MEDI4736 1500mg via IV infusion every 4 weeks for up to 3 doses/cycles Intervention: Radiation: Thoracic Radiation 5 days per week in once daily fractionation, 1.8-2.0 Gy per fraction

Intervention: Procedure/Surgery: lobectomy patients may proceed to surgery post drug and radiation intervention for lung lobectomy

Intervention: Drug: Standard of care adjuvant chemotherapy patients may or may not proceed to adjuvant chemotherapy post trial drug and radiation intervention and surgery

Drugs: Durvalumab + Tremelimumab Other Names: MEDI4736 and CP-675 MEDI4736 1500mg via IV infusion every 4 weeks for up to 3 doses/cycles + CP-675 206 75mg via IV infusion every 4 weeks up 3 doses/cycles Intervention: Radiation: Thoracic Radiation 5 days per week in once daily fractionation, 1.8-2.0 Gy per fraction Intervention: Procedure/Surgery: lobectomy patients may proceed to surgery post drug and radiation intervention for lung lobectomy

Intervention: Drug: Standard of care adjuvant chemotherapy patients may or may not proceed to adjuvant chemotherapy post trial drug and radiation intervention and surgery

1500mg via IV infusion every 4 weeks for up to 3 doses/cycles

5 days per week in once daily fractionation, 1.8-2.0 Gy per fraction

Thoracic Radiation

patients may proceed to surgery post drug and radiation intervention for lung lobectomy

lobectomy

patients may or may not proceed to adjuvant chemotherapy post trial drug and radiation intervention and surgery

Standard of care adjuvant chemotherapy

Patrick Forde, MD

This is a pilot study of neoadjuvant 'immunoradiation' (durvalumab or durvalumab plus tremelimumab) administered every 4 weeks for 2 doses, concurrently with standard thoracic radiation (RT) (45Gy in 25 fractions), with one dose of immunotherapy alone delivered in the pre-surgical window, prior to surgical resection, for patients with stage IIIA NSCLC that is deemed resectable with a lobectomy by a thoracic surgeon. If preliminary safety of the durvalumab/thoracic RT combination is established, a second cohort investigating the combination of durvalumab/tremelimumab/thoracic RT prior to surgical resection will be opened. After surgical resection, patients may receive standard adjuvant chemotherapy, as deemed appropriate by the treating investigator.

Neoadjuvant Immunoradiation for Resectable Non-Small Cell Lung Cancer

Neoadjuvant Immunoradiation for Stage III Resectable Non-Small Cell Lung Cancer

Number of participants experiencing adverse events as defined by CTCAE v4.0.

Number of participants with stage III resectable NSCLC who received durvalumab or durvalumab plus tremelimumab concurrently with thoracic radiation (RT) in the pre-surgical window prior to surgical resection, for whom planned surgical resection was not delayed.

Number of participants who experience post-operative death. Calculated through log-rank test and Cox proportional hazards (PH) model. The values in the table represent the number of participants who experienced post-operative death.

Percentage of participants with major pathologic response (MPR), partial response (PR) or no response (NR), where MPR is \>90% reduction in tumor cells, PR = 10-90% or NR = 0-10%. The percentage of patients whose tumor samples achieve MPR, PR and NR will be tabulated.

Percentage of participants with complete response (CR), partial response (PR), progressive disease (PD), and stable disease (SD) as defined by RECIST 1.1 and immune-related RECIST criteria when treated with preoperative immunoradiation followed by surgery. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions, PD is \>20% increase in sum of diameters of target lesions, SD is \<30% decrease or \<20% increase in sum of diameters of target lesions.

Time from first evidence of response until recurrence when treated with preoperative immunoradiation followed by surgery. Calculated through log-rank test and Cox proportional hazards (PH) model.

Number of months alive after treatment with preoperative immunoradiation followed by surgery. Calculated through log-rank test and Cox proportional hazards (PH) model.

AstraZeneca

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

The number of participants at risk for SAEs, AEs, and all-cause mortality is zero for the Durvalumab and Trememlimumab With Radiation arm because there were no patients enrolled onto arm 2, and no data was collected.

Drug: Durvalumab Other Names: MEDI4736

MEDI4736 1500mg via IV infusion every 4 weeks for up to 3 doses/cycles Intervention: Radiation: Thoracic Radiation 5 days per week in once daily fractionation, 1.8-2.0 Gy per fraction

Intervention: Procedure/Surgery: lobectomy patients may proceed to surgery post drug and radiation intervention for lung lobectomy

Intervention: Drug: Standard of care adjuvant chemotherapy patients may or may not proceed to adjuvant chemotherapy post trial drug and radiation intervention and surgery

Durvalumab: 1500mg via IV infusion every 4 weeks for up to 3 doses/cycles

Thoracic Radiation: 5 days per week in once daily fractionation, 1.8-2.0 Gy per fraction

lobectomy: patients may proceed to surgery post drug and radiation intervention for lung lobectomy

Standard of care adjuvant chemotherapy: patients may or may not proceed to adjuvant chemotherapy post trial drug and radiation intervention and surgery

Durvalumab With Radiation

Drugs: Durvalumab + Tremelimumab Other Names: MEDI4736 and CP-675 MEDI4736 1500mg via IV infusion every 4 weeks for up to 3 doses/cycles + CP-675 206 75mg via IV infusion every 4 weeks up 3 doses/cycles Intervention: Radiation: Thoracic Radiation 5 days per week in once daily fractionation, 1.8-2.0 Gy per fraction Intervention: Procedure/Surgery: lobectomy patients may proceed to surgery post drug and radiation intervention for lung lobectomy

Intervention: Drug: Standard of care adjuvant chemotherapy patients may or may not proceed to adjuvant chemotherapy post trial drug and radiation intervention and surgery

Durvalumab: 1500mg via IV infusion every 4 weeks for up to 3 doses/cycles

Tremelimumab: 75mg via IV infusion every 4 weeks

Thoracic Radiation: 5 days per week in once daily fractionation, 1.8-2.0 Gy per fraction

lobectomy: patients may proceed to surgery post drug and radiation intervention for lung lobectomy

Standard of care adjuvant chemotherapy: patients may or may not proceed to adjuvant chemotherapy post trial drug and radiation intervention and surgery

Durvalumab and Trememlimumab With Radiation

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Race/Ethnicity

Race/Ethnicity, Customized

Canada

United States

Region of Enrollment

The protocol planned for a second cohort for patients to be treated with durvalumab and trememlimumab with radiation, however, due to low accrual in cohort 1, there was no second cohort.

Jasmine Brooks, Senior Research Program Coordinator

all participants who were assigned to the durvalumab with radiation arm

Toxicities as Measured by Number of Participants Experiencing Adverse Events

The study closed early due to low accrual on Arm A Durvalumab with Radiation so no data was collected for Arm B Durvalumab and Trememlimumab with Radiation.

Feasibility of Preoperative Immunoradiation

The study closed to enrollment before patients could be enrolled onto Arm B: durvalumab and trememlimumab with radiation

Surgical Morbidity and Mortality

Percentage of Participants With Pathologic Response

Percentage of Participants With Radiologic Response

Duration of Response as Measured by Recurrence-free Survival

Overall Survival

Overall Study

Micronutrients

Hematinics

Vitamins

Carboplatin

Pemetrexed

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Folinic Acid

Folate

Vitamin B9

patients receiving pemetrexed, carboplatin and radiation therapy.

pemetrexed

carboplatin

thoracic radiation

Ma Sheng lin, MD

Patients with inoperable Non-Small-Cell Lung Cancer will receive thoracic radiation therapy 66 Gy over 33 fractions,and concurrent with 2 cycles of chemotherapy with pemetrexed (500 mg/m2,d1,repeated every 3 weeks)and carboplatin (AUC=5,d1,repeated every 3 weeks).

A Study of Pemetrexed Plus Carboplatin Combined With Radiation in Patients With Inoperable Locally Advanced Non-small Cell Lung Cancer (LA-NSCLC) (RT0801)

A Phase II Study of Pemetrexed Plus Carboplatin Combined With Radiation in Patients With Inoperable Locally Advanced Non-small Cell Lung Cancer

Zhejiang Cancer Hospital

Ma Shenglin, Xu Yaping

Paclitaxel

Gemcitabine

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

Antimetabolites

In this trial we adopted the approach of using both induction and concurrent chemotherapy together with TRT planned conformally to a tumor dose of 74 Gy.

Induction Chemotherapy. Weekly Carboplatin and Paclitaxel During Thoracic Radiation Therapy.

Weekly Carboplatin and Paclitaxel During Thoracic Radiation Therapy.

Radiation Therapy will begin on day 57 if there has been adequate hematologic recovery from Induction Chemotherapy.

Radiation

Gerold Bepler, MD, PhD

This is a single institution Phase II study for patients with unresectable Stage IIIA and IIIB non-small cell lung cancer. The treatment started with 2 cycles of gemcitabine and carboplatin followed by concurrent chemotherapy with radiation. The chemoradiation included using paclitaxel and carboplatin with daily thoracic radiation to a total dose of 74 Gy. Response rate was determined following the chemotherapy with gemcitabine and carboplatin and evaluated again after the chemoradiation. Treatment toxicities were also assessed.

In this trial we adopted the approach of using both induction and concurrent chemotherapy together with Thoracic Radiation Therapy (TRT) planned conformally to a tumor dose of 74 Gy. Substitution of gemcitabine for paclitaxel in the induction chemotherapy allowed us to evaluate the impact of RRM1 expression on the activity of this agent. The expression of Ribonucleotide Reductase, M1 Subunit (RRM1) was evaluated prior to initiation of therapy, following induction chemotherapy but prior to concurrent chemoradiation, and following completion of all therapy by CT-guided core needle biopsies. This is a single institution phase II clinical trial, of induction treatment with gemcitabine and carboplatin followed by concurrent chemoradiation using paclitaxel and carboplatin and daily thoracic radiation to a total dose of 74 Gy for patients with unresectable Stage IIIA and IIIB NSCLC. The specific clinical objectives of this study are as follows: To determine the response rate (both CT scan and PET scan assessment) to two cycles of induction chemotherapy with gemcitabine and carboplatin; To determine the response rate (both CT scan and PET scan assessment) to concurrent thoracic radiation and weekly paclitaxel and carboplatin; To evaluate the patterns of local and distant failure for patients treated with induction chemotherapy followed by concurrent chemoradiation according to this regimen; To estimate the median, 1 year, and overall survival; To assess acute and long term toxicities of treatment.

Induction Gemcitabine & Carboplatin Followed by Paclitaxel & Carboplatin +XRT in NSCLC

Phase II Trial of Induction Gemcitabine and Carboplatin Followed by Paclitaxel and Carboplatin With Concurrent Thoracic Radiation for Patients With Unresectable Stage IIIA/IIIB Non-Small Cell Lung Cancer

Response Rates - Complete Response (CR) + Partial Response (PR): We determined the number of participants whose response (both CT and PET assessment) to two cycles of induction chemotherapy with gemcitabine and carboplatin allowed them to proceed to chemoradiation. Response was evaluated using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee.

To determine median Progression Free Survival rate. Progression-free survival (PFS) is defined as the interval between the date of the first chemotherapy administration and the date of objective progression or death. Progression was evaluated using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee.

To determine median Overall Survival rate

The number of participants who completed all treatment on schedule without dose reductions or delays.

National Cancer Institute (NCI)

H. Lee Moffitt Cancer Center and Research Institute

Combination Therapy

Gerald Bepler, M.D., Ph.D., c/o Moffitt Cancer Center

Tolerance of Induction Therapy prior to Chemoradiation

Induction Therapy

Number of Participants Whose Response Allowed Them to Proceed to Chemoradiation

Progression Free Survival

Treatment Completion

Digestive System Diseases

Rare Diseases

Carcinoma, Squamous Cell

Esophageal Squamous Cell Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Esophageal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Esophageal Cancer

Patients in this arm will receive a treatment of Huachansu combined with thoracic radiotherapy.

Patients in this arm will receive thoracic radiotherapy alone.

Huachansu 20 ml/m2/d, intervenous infusion, once a day, 5 times per week, during the period of radiation.

Huachansu

A total dose of 61.2 Gy will be delivered in 34 fractions at 1.8 Gy/fraction, 5 fractions per week in 6.8 weeks.

This primary objective of the trial is to study whether the local control of Huachansu plus thoracic radiotherapy is better compared to thoracic radiotherapy alone for patients with esophageal squamous cell carcinoma. It's a phase II study, 134 patients are expected to be recruited into the trial.

A Study of Comparing Huachansu Plus Thoracic RT Versus RT Alone For ESCC

A Phase II Study of Comparing Huachansu Combination With Thoracic Radiotherapy Versus Radiotherapy Alone For Esophageal Squamous Cell Carcinoma

The outcome measure will be assessed by every 3-month follow-up examinations.

The survival time from date of randomization to the day of death or the last follow-up.

Measured from date of randomization until progression or death from any cause

Fudan University

Professor

Sorafenib

Protein Kinase Inhibitors

Sorafenib starting dose 200 mg orally daily + 45 Gy total in 15 radiation treatments: 3 Gy per day, 5 days a week for 3 weeks

45 Gy total in 15 radiation treatments: 3 Gy per day, 5 days a week for 3 weeks

Radiation Therapy

Zhongxing Liao, MD

The goal of this clinical research study is to find the highest safe dose of sorafenib that can be given in combination with radiation therapy to people with lung cancer. The ability of both the study drug and radiation to control the disease will also be studied.

The Study Drug:

Sorafenib is designed to block the function of important proteins in cancer cells. These proteins, when active, are in part responsible for the growth and behavior of cancer cells.

Study Drug Dose Escalation:

If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you joined this study. Up to 4 groups of 3-6 participants will be enrolled in the Phase I portion of the study.

Enrolled in the Phase I portion, the dose of sorafenib you receive will depend on when you joined this study. The first group of participants will receive the lowest dose level of sorafenib. Each new group will receive a higher dose of sorafenib than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of sorafenib is found.

All participants will receive the same type and amount of radiation.

Study Drug Administration:

You will take sorafenib capsules 1-2 times every day beginning on Day 1 of radiation therapy. If you are in the first group on study, you will take the study drug 1 time. If you are in any other groups, you will take the study drug 2 times a day. You will take the study drug without food (1 hour before or 2 hours after eating).

Radiation Therapy:

Before receiving radiation therapy, you will have a "marking session". At this visit, you will have a computed tomography (CT) scan that will be used to help to plan out the radiation therapy. This will take about 45 minutes.

Before receiving radiation, you will also have a single photon computed tomography (SPECT) scan of your lungs.

You will be given 15 radiation treatments, once a day, 5 days a week, Monday-Friday. Each treatment will take about 30 minutes. You will sign a separate consent form for radiation therapy and the procedure will be described to you in more detail.

Clinical Visits:

You will have routine clinical visits every week while receiving radiation therapy. The information collected during these clinical visit will be used for the study. At these visits, the following tests and procedures will be performed:

* You will have a physical exam, including measurement of your blood pressure and weight.
* You will be asked about any side effects you may be experiencing and any new drugs you may be taking.
* You will be asked how well you are able to perform the normal activities of daily living (performance status evaluation)
* Blood (about 3-4 teaspoons) will be drawn for routine tests.
* You will have any tests that doctor feels medically necessary

Urine will be collected every week while you are taking sorafenib and receiving radiation therapy for routine tests.

Length of Study:

You will remain on study for 6 weeks after you complete radiation therapy. You will be taken off the study early if the disease gets worse or intolerable side effects occur.

End-of-Study Visit:

You will have an end-of-study visit 4-6 weeks after you stop receiving radiation. At this visit, you will have a CT scan to check the status of the disease.

Follow-Up Visits:

Your first follow-up visit will be at 6 weeks (+/- 7 days) after radiation therapy and the second follow-up appointment will be at 10 weeks (+/- 7 days) after radiation therapy. You will then have follow up visits every 3 months. At these visits, you will go though the following:

* Your complete medical history will be recorded.
* You will have a physical exam, including measurement of your weight and blood pressure.
* You will be asked how well you are able to perform the normal activities of daily living (performance status evaluation).
* You will be asked about any drugs you may be taking.
* Blood (about 3-4 teaspoons) and urine will be collected for routine tests.
* You will also have chest x-ray.
* You will have a computed tomography (CT) scan of your chest area.
* The location, type, and size of all measurable lesions will be recorded.
* If your doctor thinks it is necessary, you will have a positron emission tomography(PET)/CT scan.
* If your doctor thinks it is necessary, you will have an electrocardiogram (ECG -- a test that measures the electrical activity of the heart).
* You may have a lung perfusion scan to see if all regions of your lung are equally functional or not. This is called lung SPECT scan.
* You will have a lung functional test (PFT) if your doctor thinks it is necessary.

All these tests are routine examinations as you would have without participating in this study in order to know the status of the disease.

This is an investigational study. Sorafenib is FDA approved and commercially available for renal cell carcinoma. The radiation therapy schedule used for this study is standard treatment for lung cancer patients. The use of sorafenib with radiation therapy is investigational.

Up to 64 patients will take part in this study. All will be enrolled at M. D. Anderson.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Neoadjuvant Immunoradiation for Resectable Non-Small Cell Lung Cancer	NCT03237377	Non-Small Cell ...	Durvalumab Tremelimumab Thoracic Radiat... lobectomy Standard of car...	18 Years - 100 Years	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
A Study of Pemetrexed Plus Carboplatin Combined With Radiation in Patients With Inoperable Locally Advanced Non-small Cell Lung Cancer (LA-NSCLC) (RT0801)	NCT00886678	Non-Small Cell ...	pemetrexed carboplatin thoracic radiat...	18 Years - 70 Years	Zhejiang Cancer Hospital
Induction Gemcitabine & Carboplatin Followed by Paclitaxel & Carboplatin +XRT in NSCLC	NCT00226590	Lung Cancer	Gemcitabine Carboplatin Paclitaxel Radiation	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
A Study of Comparing Huachansu Plus Thoracic RT Versus RT Alone For ESCC	NCT02647125	Esophageal Squa...	Huachansu thoracic radiat...	18 Years -	Fudan University
Sorafenib and Thoracic Radiation for Patients With Non-Small Cell Lung Cancer	NCT00543335	Lung Cancer	Sorafenib Radiation Thera...	18 Years -	M.D. Anderson Cancer Center
Sorafenib and Thoracic Radiation for Patients With Non-Small Cell Lung Cancer	NCT00543335	Lung Cancer	Sorafenib Radiation Thera...	18 Years -	M.D. Anderson Cancer Center
A Study of Comparing Huachansu Plus Thoracic RT Versus RT Alone For ESCC	NCT02647125	Esophageal Squa...	Huachansu thoracic radiat...	18 Years -	Fudan University
Induction Gemcitabine & Carboplatin Followed by Paclitaxel & Carboplatin +XRT in NSCLC	NCT00226590	Lung Cancer	Gemcitabine Carboplatin Paclitaxel Radiation	18 Years -	H. Lee Moffitt Cancer Center and Research Institute

Spots Global Cancer Trial Database for thoracic radiation