Symptoms and General Pathology

All Conditions

Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

Infections

Recurrence

Carcinoma

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Pneumonia

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Communicable Diseases

Respiratory Tract Infections

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Albumin-Bound Paclitaxel

Carboplatin

Tubulin Modulators

Antimitotic Agents

Group 1: Photon Therapy - 74 Gy 37 radiation treatments, given 5 days a week for about 7 1/2 weeks. Each daily treatment should take about 20-30 minutes to complete.

Paclitaxel 50 mg/m2 by vein 1 time each week for 7 weeks.

Carboplatin AUC 2 by vein 1 time each week for 7 weeks.

Group 2: Proton Therapy - 74 Gy in 2 CGE per fraction given 5 days a week for about 7 1/2 weeks.

Paclitaxel 50 mg/m2 by vein 1 time each week for 7 weeks.

Carboplatin AUC 2 by vein 1 time each week for 7 weeks.

Group 3: Receives either photon or proton therapy, whichever participant's doctor decides is better, for for 6-7 1/2 weeks.

Paclitaxel 50 mg/m2 by vein 1 time each week for 7 weeks.

Carboplatin AUC 2 by vein 1 time each week for 7 weeks.

Photon Therapy - Highest practical dose (74 CGE, 66 CGE) radiation treatments, given 5 days a week for about 7 1/2 weeks. Each daily treatment should take about 20-30 minutes to complete.

Paclitaxel 50 mg/m2 by vein 1 time each week for 7 weeks.

Carboplatin AUC 2 by vein 1 time each week for 7 weeks.

Group 1: 74 Gy 37 radiation treatments, given 5 days a week for about 7 1/2 weeks. Each daily treatment should take about 20-30 minutes to complete.

Photon Therapy

Group 2: 74 Gy in 2 CGE per fraction given 5 days a week for about 7 1/2 weeks.

Group 3: 66 Gy with conventional fractionation given 5 days a week for about 6-7 1/2 weeks.

Each daily treatment should take about 20-30 minutes to complete.

Proton Therapy

50 mg/m2 by vein 1 time each week for 7 weeks.

AUC 2 by vein 1 time each week for 7 weeks.

Zhongxing Liao, MD

The goal of this clinical research study is to learn if, compared with regular x-ray radiation, proton radiation reduces the risk of developing, treatment-related pneumonitis (TRP) or tumor recurrence (the tumor coming back in the irradiated area after treatment) in patients with lung cancer.

There are 2 types of radiation treatment being used in this study. One type of treatment is proton therapy. Proton therapy is a type of radiation therapy that uses a beam of proton particles (similar to getting an x-ray) to send radiation inside the body to the tumor. The other type of treatment is Image-Guided Adaptive Photon Therapy (IGAPT). IGAPT is a therapy that uses images to help guide the delivery of photon therapy to the tumor. Both of these types of radiation treatment are believed to help doctors to give a full dose of radiation treatment to the tumor while not damaging as much of the healthy tissue around it.

Study Groups If you are found to be eligible to take part in this study, you will go through the standard radiation treatment planning procedure, called the "marking session." After the marking session, a standard photon therapy plan (called Intensity Modulated Radiation Therapy, or IMRT) and a proton plan will be developed. If the radiation oncologist thinks that both the photon and proton plans are acceptable, you will then be randomly assigned to 1 of 2 groups. Participants in Group 1 will receive photon therapy. Participants in Group 2 will receive proton therapy.

The first 20 participants will have an equal chance to be assigned to either group. After at least 20 participants have been enrolled and there has been at least 1 occurrence of pneumonitis and/or tumor recurrence in each treatment Group, the risk of pneumonitis and/or tumor recurrence in all previous participants will be evaluated for each treatment Group, and that information will be used to calculate the chances of being assigned to either Group 1 or Group 2. This calculation will be updated after each occurrence of pneumonitis and/or tumor recurrence and after each participant returns for a follow-up visit. Once these calculations are begun, everyone who joins the study from that point on will be more likely to be assigned to the treatment Group that appears to be better in terms of pneumonitis and/or tumor recurrence.

If the tumor is too large and the standard radiation treatment plan created during the marking session is found not to be acceptable, and the radiation oncologist thinks radiation treatment it is necessary, you will still remain on study and be assigned to a third group. If you are assigned to Group 3, you will receive proton or photon treatment at a lower dose level and/or reduced length of radiation.

If you are assigned to Group 2 and your insurance provider denies reimbursement, you may chose not to receive proton therapy and receive photon therapy instead. If you chose to receive photon therapy, you will be in Group 4.

Radiation Therapy Administration Both radiation therapy treatments (photon and proton) are given through a radiation machine called an accelerator. The radiation therapy administration process is very similar to the way that a CT scan is performed. You will lay on a table and the treatment machine rotates around you without touching your body. Each daily treatment should take about 20-30 minutes to complete. Most of this time is used to position you correctly before the machine is turned on. The actual time used to give the radiation should take about 3-5 minutes each day.

While you are on this study and if you are in Groups 1 or 2, you will receive a total of 37 radiation treatments. Radiation is given 5 days a week for about 7 1/2 weeks.

If you are in Group 1, you will receive photon radiation treatment in the main hospital.

If you are in Group 2, you will receive proton therapy in the proton treatment center (PTC).

If you are in Group 3, you will receive either photon or proton therapy, whichever your doctor decides is better for you, for 6-7 1/2 weeks. If your doctor decides that photon therapy is better you will receive your treatment in the main hospital. If your doctor decides that proton therapy is better you will receive your treatment in the Proton Therapy Center.

If you are in Group 4, you will receive Photon radiation treatment in the main hospital.

Chemotherapy You will receive carboplatin and paclitaxel chemotherapy 1 time a week over 7 weeks. Each treatment will last 3-4 hours. Paclitaxel will be given by vein over 1 hour and carboplatin will be given by vein over 30 minutes. You will receive this chemotherapy combination with radiation therapy, as part of your treatment on this study.

Your chemotherapy may also be decided by your treating medical oncologist as long as the therapy is allowed by the study.

Study Visits During Chemoradiation

At least 1 time each week for all study participants, you will have study tests performed. During this weekly study visit, the following tests and procedures will be performed:

You will have a physical exam. You will be asked about any side effects you may have experienced. Blood (about 2 teaspoons) will be drawn for routine tests.

If the study doctor thinks it is needed, you will have a PET/CT scan performed to check the status of the disease during Week 4 or 5 of treatment.

Length of Study You will remain on study as long you are benefiting. You will be taken off study early if the disease gets worse, you experience intolerable side effects, or your doctor thinks that it is no longer in your best interest to receive the study treatment.

Follow-Up Visits After you have completed chemoradiation, the study staff or study nurse will contact you 1 time each month to ask you about any symptoms you may have until 6 months after chemoradiation. Each phone call should last about 10 minutes.

You will have your first follow-up visit 4-8 weeks after you have completed chemoradiation. You will have additional follow-up visits every 3-4 months for 3 years, every 6 months for the next 2 years, and then 1 time every year after that.

At the first and second follow-up visit the following tests and procedures will be performed:

You will have positron emission tomography (PET)/computed tomography (CT) scans and single proton emission tomography (SPECT) scans to check the status of your lungs and heart if the radiation or medical oncologist thinks it is necessary.

Blood (about 1 teaspoon) will be drawn for routine tests.

If the radiation oncologist or medical oncologist thinks it is needed, at the follow-up visits, you will have breathing function tests performed to check your lung function for up to 1 year after the study treatment is complete. For this test, the radiation oncologist, medical oncologist or study nurse will have you breathe into a special machine. The radiation oncologist or medical oncologist will decide how many tests are to be performed each time.

PET/CT and SPECT scans will be performed again at any time the radiation oncologist or medical oncologist thinks they are needed.

Other tests may be performed if the study doctor (radiation oncologist, medical oncologist, surgeon or pulmonologist) thinks they are needed.

This is an investigational study. Both proton radiotherapy and IGAPT are FDA approved for the treatment of lung cancer.

Up to 250 patients will take part in this multi-center research study. Up to 205 will be enrolled at M. D. Anderson.

Trial of Image-Guided Adaptive Conformal Photon vs Proton Therapy, With Concurrent Chemotherapy, for Locally Advanced Non-Small Cell Lung Carcinoma: Treatment Related Pneumonitis and Locoregional Recurrence

A Bayesian Randomized Trial of Image-Guided Adaptive Conformal Photon vs Proton Therapy, With Concurrent Chemotherapy, for Locally Advanced Non-Small Cell Lung Carcinoma: Treatment Related Pneumonitis and Locoregional Recurrence

The Primary Objective is assess and compare the incidence and time to development of CTCAE v3.0 grade \> 3 TRP, among IMRT-Group 1 or PSPT-Group 2 using Bayesian randomization. TRP will be diagnosed clinically by the treating investigator. Any questions regarding the diagnosis or grade of TRP will be resolved by the Protocol PI or by his/her designee(s). The outcomes review committee will meet to discuss each and every patient reported to have developed symptomatic TRP. The final grading of TRP will be decided by the outcomes review committee. Diagnosis of TRP included receipt of radiation that included a certain volume of normal lung, radiographic changes that suggested inflammation consistent with the radiation dose distribution within 12 months after starting chemoradiation, and symptoms attributable to TRP. Final TRP outcomes also were reviewed and approved by independent external experts.

The Primary Objective is assess and compare the incidence and time to development of local failure, among IMRT-Group 1 or PSPT-Group 2 using Bayesian randomization. Local failure was defined as treatment failure within the planning target volume plus a # 1-cm margin. Images used to report Local failure were registered with radiation dose distribution to accurately assess the location of the failure. Biopsy to confirm Local failure was strongly recommended (Data Supplement). An internal outcomes review committee reviewed each event to ensure objectivity and consistency in reporting Local failure. Final RP outcomes also were reviewed and approved by independent external experts.

1. Tumor recurrence after achieving complete response,
2. Residual tumor enlargement of 20% or more on CT according to RECIST criteria,
3. Recurrence of PET FDG Avidity after achieving complete metabolic response,
4. Increase in FDG avidity in residual tumor,
5. Pathologically proven recurrence

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

All patients on this trial will receive concurrent weekly carboplatin and paclitaxel chemotherapy with radiation therapy 74 or 66 Gy(RBE).

Intensity-modulated (Photon) Radiotherapy (IMRT)

Passive Scattering Proton Therapy (PSPT)

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

KPS≤ 80

KPS≥ 90

The KPS ranking runs from 100 to 0, where 100: "perfect" Normal health, 90: able to carry on normal activity; minor signs or symptoms of disease. 80: normal activity with effort; some signs or symptoms of disease. The KPS was to allow physicians to evaluate a patient's survival. The higher KPS scores, the better treatment outcome.

Karnofsky performance score (KPS)

Never

Ever

Smoking history

Induction chemotherapy

Adenocarcinoma

Squamous cell carcinoma

NSCLC unspecified

Large cell

Other

Tumor histology

AJCC IIA/B

AJCC IIIA

AJCC IIIB

AJCC IV

ACC Recurrence

American Joint Committee on Cancer \[AJCC\] 7th Ed:

Stage IIA: T1-2aN1M0; T2bN0M0 Stage IIB: T2b N1 M0 or T3N0M0 Stage IIIA: T1-2bN2M0 or T3N1-2M0 or T4N0-1M0 Stage IIIB: T1-3N3M0 or T4N2-3M0 Stage IV: M1 The earlier TNM staging, the better treatment outcome

Clinical disease stage (American Joint Committee on Cancer [AJCC] 7th Ed)

There were 149 out of 181 participants randomized, treated and evaluable for data analysis. 32 paticipants off-study (IMRT Arm in 13 and PSPT Arm in 19). Patient- and tumor-related characteristics did not differ between IMRT and PSPT groups.

Dr. Zhongxing Liao, MD/Professor, Radiation Oncology Department

Grade 5

Grade 4

Grade 3

The Incidence and Time to Development of Common Terminology Criteria for Adverse Events, Version 3.0 (CTCAE v3.0) Grade > 3 Treatment-related Pneumonitis (TRP)

Local Failure

Local Failure at 12 months

The Incidence and Time to Development of Local Failure (LF)

Overall Study

3-Dimensional Conformal Radiation Therapy (3D CRT)

Intensity-Modulated Radiation Therapy (IMRT)

66 Gy in 33 Daily Fractions at 2 Gy per fraction.

Intensity Modulated Radiation Therapy

3-Dimensional Conformal Radiation Therapy

Primary Objective:

* Developing Common Toxicity Criteria (CTC) 3.0 grade \> 3 treatment related pneumonitis (TRP) or
* Developing local-regional recurrence among patients treated with 3D conformal radiation therapy (CRT) (Arm 1) or intensity modulated radiation therapy (IMRT) (Arm 2).

Secondary Objectives:

* To assess and compare the time to develop CTC 3.0 grade \> 3 radiation esophagitis in patients with non-small cell lung cancer (NSCLC) treated in arm 1 and arm 2.
* To investigate the association of inflammatory cytokines with the time to the development of radiation pneumonitis and outcomes to concurrent chemoradiation between arm 1 and arm 2.
* To investigate the association of relevant pharmacogenetics, biomarkers, and gene polymorphisms with the time to the development of radiation pneumonitis and treatment outcomes to concurrent chemoradiation between arm 1 and arm 2.
* To evaluate image guided adaptive radiation therapy (IGART) using weekly computed tomography (CT) on rail or cone beam CT in the assessment of tumor response and impact on treatment planning and delivery.
* To compare overall survival, progression-free survival, median survival time, in arm 1 and arm 2.
* To evaluate the role of functional image of fluorodeoxyglucose-positron emission tomography (FDG-PET) in assessing and predicting the time to the development of TRP and tumor response.
* To measure and compare symptom burden over time of the treatment using MD Anderson Symptom Inventory (MDASI)-Lung in the 2 arms.
* To determine the impact of comorbid conditions on survival.

TRP (treatment related pneumonitis) is an inflammation (irritated or injured tissue) of the lungs that occurs as a result of chemotherapy or radiation therapy. TRP occurs because both chemotherapy and radiation affect normal lung tissue when tumors are being treated.

3D CRT is the current standard of care. It delivers radiation to several different angles of the body with center focus on the tumor(s). Because it is delivered at different angles, the same amount of radiation that contacts the tumor(s) also contacts normal lung tissue at each angle.

IMRT is a new type of radiation therapy. It also delivers radiation to several different angles of the body with center focus on the tumor(s). The difference is that the amount of treatment at each angle is adjusted according to the shape and size of the tumor(s), which in turn may decrease radiation exposure to normal lung tissue at each angle. Researchers want to find out if intensity modulated radiation therapy (IMRT) is able to decrease the amount of normal lung that is affected when treating lung cancer.

Before you can start treatment on this study, you will have "screening tests." These tests will help the doctor decide if you are eligible to take part in this study. You will have a physical exam, including measurement of your vital signs (blood pressure, heart rate, temperature, and breathing rate). You will have blood drawn (about 1 tablespoon) and urine collected for routine tests. You will be asked about any other medical problems you may have that could cause the development of TRP. You will have tests that include a computed tomography (CT) scan, positron emission tomography (PET) scan, and lung function test. A PET scan is a scan that will show cells that take in higher levels of a type of sugar (glucose), such as cancer cells. Before the scan, a small dose of a slightly radioactive form of glucose will be injected through a vein. The cells that take in higher amounts of glucose will show up better on the scan. The scanning process is quite similar to a regular CT scan. No new biopsy is needed; only the original biopsy will be used for this study.

You will have 2 different single photon-emission computed tomography tests (SPECTs). You will have a lung single-photon emission computerized tomography (SPECT)test that will show the area of blood flow in the normal lung. You will have a heart single-photon emission computerized tomography (SPECT) test that will show the areas of blood flow in the heart. To perform these single-photon emission computerized tomography (SPECT) tests, you will have a slightly radioactive substance injected into your vein so that images can be seen of the blood flow in the lung and heart. This will help the study doctor try to avoid using radiation angles that would go through the normal blood flow area. You will also have a biopsy of your tumor tissue. To perform a tumor biopsy, an area of the body (where tumor is present) is numbed with anesthetic, and a small amount of tumor tissue is withdrawn through a large needle or with forceps (a tong-like instrument) during an endoscopic (viewing of body cavity with a special instrument) exam.

Researchers will use the results of these tests to learn the stage (size and location) of the cancer to see if the tumor(s) can be treated by radiation. Women who are able to have children must have a blood or urine pregnancy test, which will be performed on the same blood or urine that was collected for routine tests. To be eligible to take part in this study, the pregnancy test must be negative.

If you are found to be eligible to take part in this study, your radiation doctor will first conduct a planning session. You will have a CT scan of your chest, and your respiratory (breathing) motion will be monitored. After the scan is done, your radiation doctor will evaluate it and make an outline of the tumor(s) in your lung. The CT scan helps the doctor identify (note the difference between) the tumor(s) and the normal surrounding tissue. The planning session helps the radiation doctor decide the target area(s), the best angles to deliver the radiation, and the most effective radiation dose (which is also intended to decrease radiation to surrounding normal tissues) for treatment.

If the plan for treatment is considered acceptable for you by the radiation doctor, you will then be randomly assigned (as in the toss of a coin) to 1 of 2 treatment groups. Participants in one group will receive 3D CRT. Participants in the other group will receive intensity modulated radiation therapy (IMRT). You will have an equal chance of being in either one of these groups. If you are assigned to receive intensity modulated radiation therapy (IMRT), the total radiation dose to the tumor(s) will be slightly higher than for participants receiving 3D CRT.

If the 3D CRT plan for treatment is not considered acceptable for you (usually because of a large target area) by the radiation doctor, you will be treated with IMRT, with or without amifostine. Amifostine is a drug given as an injection to protect the normal lung and esophagus tissue from radiation side effects and injury. Your treating physician will decide if you need amifostine or not, based on the size of the tumor tissue and normal tissue in the radiation "field" (the area given radiation during treatment). If you need amifostine, a nurse will give you the injection about 30 minutes before radiation treatment. Your blood pressure will be checked for 15-20 minutes after injection.

Participants on this study will be receiving standard chemotherapy given together with radiation therapy. The standard chemotherapy usually includes cisplatin, carboplatin, paclitaxel, or docetaxel. The chemotherapy is not considered the investigational part of this study.

All study participants will receive standard chemotherapy, given together with radiation therapy. The standard chemotherapy usually includes cisplatin, carboplatin, paclitaxel, and/or docetaxel. Your chemotherapy doctor will explain the side effects of these chemotherapy drugs to you before you start receiving chemotherapy. The chemotherapy is not the investigational part of this clinical trial.

Participants in each group will receive a total of 6 ½ weeks of radiation therapy (once a day for 5 days a week). You will not be treated on the weekends or on a national holiday. If the disease gets worse or you experience any intolerable side effects, you will be taken off this study.

After you have completed therapy on this study, you will have follow-up visits. The study doctor will check how the disease responded to treatment using the same imaging scans and blood tests (about 1 tablespoon each time) that were performed during the screening portion of this study. These tests will be performed about every 3-4 months after completion of treatment as part of your standard of care.

This is an investigational study. Both 3D conformal radiation therapy (CRT) and intensity modulated radiation therapy (IMRT) are FDA approved for the treatment of cancer. Up to 168 patients will take part in this study. All will be enrolled at M.D. Anderson.

3-Dimensional Conformal Radiation Therapy Versus Intensity Modulated Radiation Therapy

A Randomized Trial to Compare Time to Common Toxicity Criteria for Adverse Effect (CTC AEC) 3.0 Grade. 3 Treatment Related Pneumonitis (TRP) in Patients With Locally Advanced Non-Small Cell Lung Carcinoma (NSCLC) Receiving Concurrent Chemoradiation Radiation Treated With 3-Dimensional Conformal Radiation Therapy (3D CRT, ARM 1) Versus Intensity Modulated Radiation Therapy (IMRT, ARM 2) Using 4-Dimensional CT Planning and Image Guided Adaptive Radiation Therapy (IGART)

Time to treatment failure defined as from the time of randomization to the development of treatment related pneumonitis (TRP) or local-regional recurrence, whichever occurs first.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Trial of Image-Guided Adaptive Conformal Photon vs Proton Therapy, With Concurrent Chemotherapy, for Locally Advanced Non-Small Cell Lung Carcinoma: Treatment Related Pneumonitis and Locoregional Recurrence	NCT00915005	Non-Small-Cell ...	Photon Therapy Proton Therapy Paclitaxel Carboplatin	18 Years - 85 Years	M.D. Anderson Cancer Center
Trial of Image-Guided Adaptive Conformal Photon vs Proton Therapy, With Concurrent Chemotherapy, for Locally Advanced Non-Small Cell Lung Carcinoma: Treatment Related Pneumonitis and Locoregional Recurrence	NCT00915005	Non-Small-Cell ...	Photon Therapy Proton Therapy Paclitaxel Carboplatin	18 Years - 85 Years	M.D. Anderson Cancer Center
3-Dimensional Conformal Radiation Therapy Versus Intensity Modulated Radiation Therapy	NCT00520702	Lung Cancer	Intensity Modul... 3-Dimensional C...	18 Years - 80 Years	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for treatment related pneumonitis