Neoplasms

All Conditions

Digestive System Diseases

Rare Diseases

Behaviors and Mental Disorders

Carcinoma

Carcinoma, Squamous Cell

Adenocarcinoma

Esophageal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Esophageal Cancer

Quality of Life

Radiation therapy 1 time each day, 5 days a week (Monday through Friday) for up to 28 treatments. 1.8 Gy (or at RBE ("Relative Biologic Equivalence" for PBT)) to be delivered to the periphery of the planning target volume (PTV).

Radiation therapy 1 time each day, 5 days a week (Monday through Friday) for up to 28 treatments. 1.8 Gy to be delivered to the periphery of the planning target volume (PTV).

1.8 Gy (Relative Biologic Equivalence ((RBE)) to be delivered to the periphery of the planning target volume (PTV) 1 time each day, 5 days a week (Monday through Friday) for up to 28 treatments.

Proton Beam Therapy (PBT)

1.8 Gy to be delivered to the periphery of the planning target volume (PTV) 1 time each day, 5 days a week (Monday through Friday) for up to 28 treatments.

Intensity Modulated Radiation Therapy (IMRT)

Symptom and Quality of Life questionnaires completed at baseline, every week during radiation therapy, during break after radiation therapy, and during follow up phase.

Questionnaires

Steven H. Lin, MD,PHD

The goal of this clinical research study is to learn how safe and effective proton-beam therapy (PBT) may be in comparison to intensity modulated radiation therapy (IMRT) in combination with chemotherapy in patients with esophageal cancer.

PBT and IMRT are both forms of radiation therapy that are designed to treat a specific area of the body while affecting as little of the surrounding normal tissue as possible. PBT is a newer technology that is designed to further reduce the amount of radiation that affects the surrounding normal tissue. However, this is still being studied.

Study Treatment:

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the flip of a coin) to 1 of 2 study groups:

* If you are in Group 1, you will receive IMRT.
* If you are in Group 2, you will receive PBT.

You will receive radiation therapy 1 time each day, 5 days a week (Monday through Friday) for up to 28 treatments.

Your doctor may think it is in your best interest to also receive chemotherapy while you are receiving radiation therapy. If this occurs, you will sign a separate consent form for these drugs with a full description of how they are given and the risks they may cause.

Study Visits:

Before you begin receiving radiation therapy, you will have a baseline visit. The following tests and procedures will be performed:

* Blood (about 1-2 tablespoons) will be drawn for routine tests.
* Your performance status will be recorded.
* You will have a PET/CT or CT scan to check the status of the disease.
* You will have lung function tests
* You will complete the symptom and quality of life questionnaires.
* Your esophagus will be examined using an endoscope. If the doctor thinks it is needed, you will have a biopsy to check the status of the disease.

You will then have a study visit every week while you are receiving radiation therapy. The following tests and procedures will be performed:

* Your medical history will be recorded.
* You will have a physical exam.
* Your performance status, weight, and vital signs will be recorded.
* Blood (about 1-2 tablespoons) will be drawn for routine tests.
* You will complete the symptom and quality of life questionnaires.

Length of Study:

You will receive radiation therapy for up to 28 treatments (about 5½ weeks). You will no longer be able to receive radiation therapy if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Your participation on the study will be over once you have completed the follow-up visits.

Follow-Up:

After you stop receiving radiation therapy, there will be a 4-6 week break. During this time, you will contacted 2 times each week to complete the symptom and quality of life questionnaires. You will receive a call from an automated calling service or from the study staff at a scheduled time of your choosing. You will continue to be followed routinely during treatment and for follow-up visits and tests.

About 4-6 weeks after you stop receiving radiation therapy, the following tests and procedures will be performed:

* Your medical history will be recorded.
* You will have a physical exam.
* Your performance status, weight, and vital signs will be recorded.
* You will have a PET/CT scan to check the status of the disease.
* You will have lung function tests.
* Blood (about 1-2 tablespoons) will be drawn for routine tests.
* You will complete the symptom and quality of life questionnaires.
* Your esophagus will be examined using an endoscope. If the doctor thinks it is needed, you will have a biopsy to check the status of the disease.

If your doctor thinks it is in your best interest after you have completed radiation therapy, you will have surgery to remove the tumor. You will sign a separate consent form that describes the procedure and its risks. As part of this study, the study doctor will check you for side effects and discomfort after the surgery.

Every 3-4 months for 2 years, and then every 4-6 months for the next 3 years, you will have follow-up visits. The following tests and procedures will be performed:

* Your medical history will be recorded.
* You will have a physical exam.
* Your performance status, weight, and vital signs will be recorded.
* You will have either a CT or a PET/CT scan to check the status of the disease.
* You will complete the symptom and quality of life questionnaires. (If the disease gets worse, these questionnaires will no longer be completed.)

Additionally, the following tests and procedures will be performed at follow-up visits only when the doctor thinks they are needed:

* Blood (about 1-2 tablespoons) may be drawn for routine tests.
* You may have lung function tests.
* Your esophagus will be examined using an endoscope. If the doctor thinks it is needed, you will have a biopsy to check the status of the disease.

You may be contacted by the study staff to ask about your health, even if you choose not to return to MD Anderson for follow-up visits after completing treatment for esophageal cancer.

This is an investigational study. IMRT and PBT are delivered using FDA-approved and commercially available methods. It is investigational to compare IMRT to PBT.

Up to 180 patients will take part in this study. All will be enrolled at MD Anderson.

Proton Beam Therapy (PBT) Versus Intensity-Modulated Radiation Therapy (IMRT) Trial

Phase IIB Randomized Trial of Proton Beam Therapy Versus Intensity-Modulated Radiation Therapy for the Treatment of Esophageal Cancer

Defined from the time of enrollment to the date of death or any recurrence. The progression-free survival (PFS) time distribution will be estimated in each treatment arm using the Kaplan-Meier method.

TTB defined from the time of randomization to 12 months after randomization. Total toxicity burden (TTB) is computed as a composite score from serious adverse events (SAEs) and, among patients who undergo surgery, postoperative complications (POCs).

Massachusetts General Hospital

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Symptoms and General Pathology

Gland and Hormone Related Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Ear, Nose, and Throat Diseases

Recurrence

Thyroid Diseases

Squamous Cell Carcinoma of Head and Neck

Laryngeal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Hematinics

Vitamins

Pemetrexed

Cetuximab

Cisplatin

Folic Acid

Vitamin B Complex

Vitamin B 12

Hydroxocobalamin

Parathyroid Hormone

Trace Elements

Enzyme Inhibitors

Folic Acid Antagonists

Antineoplastic Agents, Immunological

Folinic Acid

Methylcobalamin

Folate

Vitamin B9

Vitamin B12

Cobalamin

Cyanocobalamin

Participants will receive pemetrexed,cisplatin and cetuximab for up to 6 cycles (21 days per cycle) followed by optional maintenance of pemetrexed and cetuximab until disease progression. Optional maintenance therapy is permitted after at least 4 cycles of triplet combination therapy have been given. Cetuximab will be administered as an initial dose of 400 milligram per meter squared (mg/m\^2) intravenous (IV) infusion and as a 250 mg/m\^2 IV weekly dose thereafter.

As Standard of care dietary supplements included: 350 to 1000 micrograms (µg) oral Folic Acid 5 times a day for the 7 days preceding the first dose of first dose of pemetrexed and continuing throughout treatment and for 21 days after the last dose of pemetrexed and 1000 µg vitamin B12 intramuscular injection (IM) during the week preceding the first dose of pemetrexed and every 9 weeks thereafter.

Triplet Combination Therapy: 500 mg/m\^2 administered intravenously on Day 1 of 21 day cycle for up to 6 cycles

Maintenance Therapy: 500mg/m\^2 administered intravenously on Day 1 of 21 day cycle until disease progression or unacceptable toxicity

Triplet Combination Therapy: 400 mg/m\^2 administered intravenously on Day 1 of 21 day cycle for 1 cycle; 250 mg/m\^2 administered IV infusion on Day 1 of 21 day cycle and then weekly for up to 6 cycles.

Maintenance Therapy: 250 mg/m\^2 administered intravenously on Day 1 of 21 day cycle and then weekly until disease progression or unacceptable toxicity

Triplet Combination Therapy: 75mg/m\^2 administered intravenously on Day 1 of 21 day cycle for up to 6 cycles.

Standard of care dietary supplements: 350 to 1000 µg orally 5 times a day for the 7 days preceding the first dose of first dose of pemetrexed and continuing throughout treatment and for 21 days after the last dose of pemetrexed.

Standard of care dietary supplements: 1000 µg IM during the week preceding the first dose of pemetrexed and every 9 weeks thereafter.

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5PM Eastern time (UTC/GMT - 5 hours, EST

The purpose of this trial is to estimate progression free survival in patients with recurrent or metastatic head and neck cancer that have not received chemotherapy in this setting.

A 12 patient safety lead will evaluate side effects in patients receiving at least 2 cycles of the combination pemetrexed, cisplatin and cetuximab.

A Study for Patients With Recurrent or Metastatic Squamous Cell Head and Neck Cancer

Phase 2 Study of Pemetrexed in Combination With Cisplatin and Cetuximab in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

PFS based on Response Evaluation Criteria in Solid Tumors (RECIST) Guidelines defined as the time from the date of first dose of study drug to first documented objective progressive disease (PD) or death from any cause. PD is defined as at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

OS defined as the time from the date of first dose of study drug to the date to death from any cause.

CR and PR based on RECIST Guidelines: CR is defined as the disappearance of all tumor lesions; PR is defined as at least a 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LDs or the complete disappearance of target lesions, with persistence (but not worsening) of one or more nontarget lesions and the appearance of no new lesions. PD is defined as at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

Vertical VAS - a 20 millimeter (mm), fractionated scale in the form of a thermometer with endpoints of 0 (worst imaginable health state) and 100 (best imaginable health state). Participants used the EQ-5D VAS scale to rate their overall health on the day the questionnaire was administered. Possible change values range from -100 (best imaginable health at baseline changed to worst possible health at visit) to 100 (worst possible health at baseline changed to best possible health at visit).

EQ-5D Index is derived by converting the Descriptive System (participant is required to rate health by checking 1 \[no limitation\], 2 \[some limitation\] or 3 \[severe or complete limitation\] in 5 dimensions \[mobility, self-care, usual activities, pain/comfort and anxiety/depression\]) to a single summary index. A utility value assigned to each individual's health state based on the absence or presence of moderate or severe problems in the 5 dimensions. A regression equation defines a utility value for these health states. The possible values for health utility ranged from -0.59 (severe problems in all 5 dimensions) to 1 (no problem in all dimensions) on a scale where 0 represents death and 1 represents the best possible health state. Possible change values range from -1.59 (no problems at baseline to severe problems at visit) to 1.59 (severe problems at baseline to no problems at visit).

PSS-HNC is a clinician-rated instrument designed to measure speaking and eating disabilities of participants with head and neck cancer and consists of 3 subscales: Normalcy of Diet (NOD) subscale measures the ability of the participants to eat a normal diet, scale ranged from 0 (non-oral feeding) to 100 (unrestricted diet); Understandability of Speech (UOS)subscale measured the degree a clinician was able to understand the participant's speech, subscale ranged from 0 (never understandable) to 100 (always understandable); Eating in Public (EIP) subscale, rating based on clinician question to the participant to report who he/she eats with and in what setting, subscale ranged from 0 (always eats alone) to 100 (no restriction of place, food, or companion). Change from baseline: negative value represents a decrease in function and a positive value represents an increase in function.

Eli Lilly and Company

Pemetrexed 500 mg/m\^2 administered by IV infusion followed by cisplatin 75 mg/m\^2 administered by IV infusion both given on Day 1 of each 21 day cycle. Cetuximab 400 mg/m\^2 administered by IV infusion initially as a loading dose in Week 1, subsequent weeks cetuximab 250 mg/m\^2 administered by IV infusion once per week for a maximum of six 21 day cycles. At the discretion of the investigator participants who completed at least 4 cycles of triplet combination therapy could continue to receive pemetrexed plus cetuximab in the maintenance setting or as a monotherapy of pemetrexed or cetuximab alone in the absence of PD, unacceptable toxicity or any other withdrawal criterion up to 19 months. Participants also received Folic Acid and Vitamin B12 as standard of care dietary supplements.

Pemetrexed Cisplatin Cetuximab

Age Continuous

Sex: Female, Male

White

Race/Ethnicity, Customized

Belgium

France

Germany

Italy

Spain

United Kingdom

Region of Enrollment

Chief Medical Officer

Protocol Qualified (PQ) Population: all randomized and treated participants

Progression Free Survival (PFS)

PQ Population: all randomized and treated participants

Overall Survival (OS)

PQ Population: all randomized and treated participants with evaluable data; 6 participant's results were unknown.

Percent of Participants With a Partial Response (PR) or a Complete Response (CR)

Change at End of Triplet Therapy (n=23)

Change at End of Maintenance Therapy (n=11)

PQ Population: all randomized and treated participants with evaluable data for each category

Change From Baseline in Participant Reported European-Quality of Life 5 Dimension Instrument (EQ-5D) Visual Analog Scale (VAS) at End of Triplet Combination Therapy and End of Maintenance Therapy

Change at End of Triplet Therapy (n=29)

Change at End of Maintenance Therapy (n=15)

PQ Population: all randomized and treated participants with EQ-5D data at respective timepoint.

Change From Baseline in Participant Reported EQ-5D Utility Score at End of Triplet Combination Therapy and End of Maintenance Therapy

NOD-Change at Triplet Cycle 2 (n=53)

NOD-Change at Triplet Cycle 4 (n=41)

NOD-Change at Triplet Cycle 6 (n=24)

NOD-Change at Maintenance Cycle 1 (n=23)

NOD-Change at Maintenance Cycle 3 (n=10)

NOD-Change at Maintenance Cycle 5 (n=6)

NOD-Change at Maintenance Cycle 7 (n=5)

EIP-Change at Triplet Cycle 2 (n=46)

EIP-Change at Triplet Cycle 4 (n=37)

EIP-Change at Triplet Cycle 6 (n=22)

EIP-Change at Maintenance Cycle 1 (n=23)

EIP-Change at Maintenance Cycle 3 (n=10)

EIP-Change at Maintenance Cycle 5 (n=6)

EIP-Change at Maintenance Cycle 7 (n=5)

UOS-Change at Triplet Cycle 2 (n=53)

UOS-Change at Triplet Cycle 4 (n=41)

UOS-Change at Triplet Cycle 6 (n=24)

UOS-Change at Maintenance Cycle 1 (n=23)

UOS-Change at Maintenance Cycle 3 (n=10)

UOS-Change at Maintenance Cycle 5 (n=6)

UOS-Change at Maintenance Cycle 7 (n=5)

PQ Population: all randomized and treated participants with evaluable data at respective timepoint.

Change From Baseline in Performance Status Scale for Head and Neck Cancer Patients (PSS-HNC)

Pemetrexed 500 milligram per meter squared (mg/m\^2) administered by intravenous (IV) infusion followed by cisplatin 75 mg/m\^2 administered by IV infusion both given on Day 1 of each 21 day cycle. Cetuximab 400 mg/m\^2 administered by IV infusion initially as a loading dose in Week 1, subsequent weeks cetuximab 250 mg/m\^2 administered by IV infusion once per week for a maximum of six 21 day cycles.

At the discretion of the investigator participants who completed at least 4 cycles of triplet combination therapy could continue to receive pemetrexed plus cetuximab in the maintenance setting or as a monotherapy of pemetrexed or cetuximab alone in the absence of PD, unacceptable toxicity or any other withdrawal criterion up to 19 months.

Participants also received Folic Acid and Vitamin B12 as standard of care dietary supplements.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Proton Beam Therapy (PBT) Versus Intensity-Modulated Radiation Therapy (IMRT) Trial	NCT01512589	Esophageal Canc...	Proton Beam The... Intensity Modul... Questionnaires	18 Years -	M.D. Anderson Cancer Center
A Study for Patients With Recurrent or Metastatic Squamous Cell Head and Neck Cancer	NCT01057589	Head and Neck N...	Pemetrexed Cetuximab Cisplatin Folic Acid Vitamin B12	18 Years -	Eli Lilly and Company
A Study for Patients With Recurrent or Metastatic Squamous Cell Head and Neck Cancer	NCT01057589	Head and Neck N...	Pemetrexed Cetuximab Cisplatin Folic Acid Vitamin B12	18 Years -	Eli Lilly and Company
Proton Beam Therapy (PBT) Versus Intensity-Modulated Radiation Therapy (IMRT) Trial	NCT01512589	Esophageal Canc...	Proton Beam The... Intensity Modul... Questionnaires	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for cervical esophagus