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Comparing Proton Therapy to Photon Radiation Therapy for Esophageal Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03801876
Recruitment Status : Recruiting
First Posted : January 14, 2019
Last Update Posted : October 8, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
NRG Oncology

Brief Summary:
This trial studies how well proton beam radiation therapy compared with intensity modulated photon radiotherapy works in treating patients with stage I-IVA esophageal cancer. Proton beam radiation therapy uses a beam of protons (rather than x-rays) to send radiation inside the body to the tumor without damaging much of the healthy tissue around it. Intensity modulated photon radiotherapy uses high-energy x-rays to deliver radiation directly to the tumor without damaging much of the healthy tissue around it. It is not yet known whether proton beam therapy or intensity modulated photon radiotherapy will work better in treating patients with esophageal cancer.

Condition or disease Intervention/treatment Phase
Clinical Stage I Esophageal Adenocarcinoma AJCC v8 Clinical Stage I Esophageal Squamous Cell Carcinoma AJCC v8 Clinical Stage I Gastroesophageal Junction Adenocarcinoma AJCC v8 Clinical Stage II Esophageal Adenocarcinoma AJCC v8 Clinical Stage II Esophageal Squamous Cell Carcinoma AJCC v8 Clinical Stage II Gastroesophageal Junction Adenocarcinoma AJCC v8 Clinical Stage IIA Esophageal Adenocarcinoma AJCC v8 Clinical Stage IIA Gastroesophageal Junction Adenocarcinoma AJCC v8 Clinical Stage IIB Esophageal Adenocarcinoma AJCC v8 Clinical Stage IIB Gastroesophageal Junction Adenocarcinoma AJCC v8 Clinical Stage III Esophageal Adenocarcinoma AJCC v8 Clinical Stage III Esophageal Squamous Cell Carcinoma AJCC v8 Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8 Clinical Stage IVA Esophageal Adenocarcinoma AJCC v8 Clinical Stage IVA Esophageal Squamous Cell Carcinoma AJCC v8 Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8 Pathologic Stage I Esophageal Adenocarcinoma AJCC v8 Pathologic Stage I Esophageal Squamous Cell Carcinoma AJCC v8 Pathologic Stage I Gastroesophageal Junction Adenocarcinoma AJCC v8 Pathologic Stage IA Esophageal Adenocarcinoma AJCC v8 Pathologic Stage IA Esophageal Squamous Cell Carcinoma AJCC v8 Pathologic Stage IA Gastroesophageal Junction Adenocarcinoma AJCC v8 Pathologic Stage IB Esophageal Adenocarcinoma AJCC v8 Pathologic Stage IB Esophageal Squamous Cell Carcinoma AJCC v8 Pathologic Stage IB Gastroesophageal Junction Adenocarcinoma AJCC v8 Pathologic Stage IC Esophageal Adenocarcinoma AJCC v8 Pathologic Stage IC Gastroesophageal Junction Adenocarcinoma AJCC v8 Pathologic Stage II Esophageal Adenocarcinoma AJCC v8 Pathologic Stage II Esophageal Squamous Cell Carcinoma AJCC v8 Pathologic Stage II Gastroesophageal Junction Adenocarcinoma AJCC v8 Pathologic Stage IIA Esophageal Adenocarcinoma AJCC v8 Pathologic Stage IIA Esophageal Squamous Cell Carcinoma AJCC v8 Pathologic Stage IIA Gastroesophageal Junction Adenocarcinoma AJCC v8 Pathologic Stage IIB Esophageal Adenocarcinoma AJCC v8 Pathologic Stage IIB Esophageal Squamous Cell Carcinoma AJCC v8 Pathologic Stage IIB Gastroesophageal Junction Adenocarcinoma AJCC v8 Pathologic Stage III Esophageal Adenocarcinoma AJCC v8 Pathologic Stage III Esophageal Squamous Cell Carcinoma AJCC v8 Pathologic Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8 Pathologic Stage IIIA Esophageal Adenocarcinoma AJCC v8 Pathologic Stage IIIA Esophageal Squamous Cell Carcinoma AJCC v8 Pathologic Stage IIIA Gastroesophageal Junction Adenocarcinoma AJCC v8 Pathologic Stage IIIB Esophageal Adenocarcinoma AJCC v8 Pathologic Stage IIIB Esophageal Squamous Cell Carcinoma AJCC v8 Pathologic Stage IIIB Gastroesophageal Junction Adenocarcinoma AJCC v8 Pathologic Stage IVA Esophageal Adenocarcinoma AJCC v8 Pathologic Stage IVA Esophageal Squamous Cell Carcinoma AJCC v8 Pathologic Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8 Postneoadjuvant Therapy Stage I Esophageal Adenocarcinoma AJCC v8 Postneoadjuvant Therapy Stage I Esophageal Squamous Cell Carcinoma AJCC v8 Postneoadjuvant Therapy Stage I Gastroesophageal Junction Adenocarcinoma AJCC v8 Postneoadjuvant Therapy Stage II Esophageal Adenocarcinoma AJCC v8 Postneoadjuvant Therapy Stage II Esophageal Squamous Cell Carcinoma AJCC v8 Postneoadjuvant Therapy Stage II Gastroesophageal Junction Adenocarcinoma AJCC v8 Postneoadjuvant Therapy Stage III Esophageal Adenocarcinoma AJCC v8 Postneoadjuvant Therapy Stage III Esophageal Squamous Cell Carcinoma AJCC v8 Postneoadjuvant Therapy Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8 Postneoadjuvant Therapy Stage IIIA Esophageal Adenocarcinoma AJCC v8 Postneoadjuvant Therapy Stage IIIA Esophageal Squamous Cell Carcinoma AJCC v8 Postneoadjuvant Therapy Stage IIIA Gastroesophageal Junction Adenocarcinoma AJCC v8 Postneoadjuvant Therapy Stage IIIB Esophageal Adenocarcinoma AJCC v8 Postneoadjuvant Therapy Stage IIIB Esophageal Squamous Cell Carcinoma AJCC v8 Postneoadjuvant Therapy Stage IIIB Gastroesophageal Junction Adenocarcinoma AJCC v8 Postneoadjuvant Therapy Stage IVA Esophageal Adenocarcinoma AJCC v8 Postneoadjuvant Therapy Stage IVA Esophageal Squamous Cell Carcinoma AJCC v8 Postneoadjuvant Therapy Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8 Thoracic Esophagus Squamous Cell Carcinoma Drug: Carboplatin Procedure: Esophagectomy Radiation: Intensity-Modulated Radiation Therapy Drug: Paclitaxel Radiation: Proton Beam Radiation Therapy Other: Quality-of-Life Assessment Other: Questionnaire Administration Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase III Randomized Trial of Proton Beam Therapy (PBT) Versus Intensity Modulated Photon Radiotherapy (IMRT) for the Treatment of Esophageal Cancer
Actual Study Start Date : March 15, 2019
Estimated Primary Completion Date : February 1, 2027
Estimated Study Completion Date : February 2032

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Group I (PBT, paclitaxel, carboplatin, esophagectomy)
Patients undergo PBT over 28 fractions 5 days a week for 5.5 weeks to a total dose of 50.4 Gy. Patients also receive paclitaxel (50 mg/m^2) IV and carboplatin (AUC=2 [maximum 300 mg]) IV on days 1, 8, 15, 22, 29, and 36 while undergoing PBT. Within 4-8 weeks after completion of chemotherapy and radiation therapy, patients may undergo an esophagectomy per physician discretion.
Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo

Procedure: Esophagectomy
Undergo esophagectomy
Other Name: excision of the esophagus

Drug: Paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol
  • Taxol Konzentrat

Radiation: Proton Beam Radiation Therapy
Undergo PBT
Other Names:
  • PBRT
  • Proton Radiation Therapy

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Other: Questionnaire Administration
Ancillary studies

Active Comparator: Group II (IMRT, paclitaxel, carboplatin, esophagectomy)
Patients undergo IMRT over 28 fractions 5 days a week for 5.5 weeks to a total dose of 50.4 Gy. Patients also receive paclitaxel (50 mg/m^2) IV and carboplatin (AUC=2 [maximum 300 mg]) IV on days 1, 8, 15, 22, 29, and 36 while undergoing IMRT. Within 4-8 weeks after completion of chemotherapy and radiation therapy, patients may undergo an esophagectomy per physician discretion.
Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo

Procedure: Esophagectomy
Undergo esophagectomy
Other Name: excision of the esophagus

Radiation: Intensity-Modulated Radiation Therapy
Undergo IMRT
Other Names:
  • IMRT
  • Intensity Modulated RT
  • Intensity-Modulated Radiotherapy

Drug: Paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol
  • Taxol Konzentrat

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Other: Questionnaire Administration
Ancillary studies




Primary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: From the date of randomization to the date of death due to any cause or date of last follow-up for patients without an OS event reported. This analysis occurs after 173 deaths; estimated to occur 4 years after accrual completion ]
    Will be estimated by the Kaplan-Meier method. The distributions of OS between treatment arms will be compared using the log rank test.

  2. Incidence of specific grade 3+ cardiopulmonary adverse events (AEs) that are definitely, probably, or possibly related to protocol treatment [ Time Frame: From baseline up to 8 years ]
    Will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. Difference in proportion of defined cardiopulmonary AEs will be analyzed with a chi-squared test.


Secondary Outcome Measures :
  1. Pathologic response rate [ Time Frame: At time of surgery ]
    A Chi-square test will be used to compare the pathologic response rates between the treatment arms.

  2. Grade 4 lymphopenia during chemoradiation [ Time Frame: From the start of chemoradiation to the end of chemoradiation treatment assessed up to 31 days ]
    Will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. The proportion of patients experiencing grade 4 lymphopenia during chemoradiation will be compared between treatment arms using a chi-squared test.

  3. Lymphocyte counts [ Time Frame: From the last date of chemoradiation up to 8 weeks post chemoradiation ]
    Mean lymphocyte counts at first post chemoradiation follow-up will be compared between treatment arms using a t-test. If the data do not satisfy the normality assumption, a Wilcoxin test may be used instead.

  4. Locoregional failure (LRF) [ Time Frame: From the date of randomization to the date of first LRF or date of last follow-up for patients without an LRF event reported, assessed up to 8 years ]
    Will be defined as local/regional recurrence or progression. Will be estimated by the cumulative incidence method, with death as a competing risk. The distribution of LRF estimates between the two arms will be compared using Gray?s test. The Fine-Gray regression model will be used to analyze the effects of factors, in addition to treatment, which may be associated with LRF.

  5. Distant metastatic-free survival (DMFS) [ Time Frame: From the date of randomization to the date of first DMFS failure or last follow-up for patients without a reported DMFS event, assessed up to 8 years ]
    Will be defined as appearance of distant metastasis or death due to any cause. Will be estimated by the Kaplan-Meier method and estimates between the two treatment arms will be compared using the log rank test. The Cox proportional hazard regression model will be used to analyze the effects of factors, in addition to treatment, which may be associated with DMFS.

  6. Progression-free survival [ Time Frame: From the date of randomization to the date of first PFS failure or last follow-up for patients without a reported PFS event, assessed up to 8 years ]
    Will be defined as appearance of local/regional/distant failure or death due to any cause. Will be estimated by the Kaplan-Meier method and estimates between the two treatment arms will be compared using the log rank test. The Cox proportional hazard regression model will be used to analyze the effects of factors, in addition to treatment, which may be associated with PFS.

  7. Quality-adjusted life years (QALY) [ Time Frame: Assessed up to 8 years ]
    Will be evaluated and compared using EuroQol five-dimensional questionnaire (EQ-5D) only if the primary endpoint is met.

  8. Cost-benefit economic analysis of treatment [ Time Frame: Assessed up to 8 years ]
    Will be calculated by the visual analog scale (VAS) and index scores form the EQ-5D-5L only be done if primary endpoint is met. Will be compared between treatment arms using a t-test with a 2-sided significance level of 0.05. If there are significant differences, then a cost analysis will be conducted.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • PRIOR TO STEP 1 REGISTRATION:
  • Histologically proven diagnosis of adenocarcinoma or squamous cell carcinoma of the thoracic esophagus or gastroesophageal junction (Siewert I-II)
  • Stage I-IVA, excluding T4b, according to the American Joint Committee on Cancer (AJCC) 8th edition based on the following diagnostic workup:

    • History/physical examination
    • Whole-body fludeoxyglucose F-18 (FDG)-positron emission tomography (PET)/computed tomography (CT) with or without (+/-) contrast (preferred) or chest/abdominal (include pelvic if clinically indicated) CT with contrast

      • For patients who DID NOT receive induction chemotherapy, scan must occur within 30 days prior to Step 1 registration
      • For patients who DID receive induction chemotherapy, scan must occur:

        • Within 30 days after final induction chemotherapy dose; OR
        • Within 30 days prior to Step 1 registration
      • Note: Patients who had prior endoscopic mucosal resection (EMR) with a diagnosis of AJCC stage I-IVA, excluding T4b, esophageal cancer are eligible
  • Surgical consultation to determine whether or not the patient is a candidate for resection after completion of chemoradiation
  • Induction chemotherapy for the current malignancy prior to concurrent chemoradiation allowed if last dose is no more than 90 days and no less than 10 days prior to Step 1 registration
  • Zubrod performance status 0, 1, or 2
  • Absolute neutrophil count (ANC) (within 30 days prior to Step 1 registration)

    • For patients who DID NOT receive induction chemotherapy: ANC >= 1,500 cells/mm^3
    • For patients who DID receive induction chemotherapy: ANC >= 1,000 cells/mm^3
  • Platelets (within 30 days prior to Step 1 registration)

    • For patients who DID NOT receive induction chemotherapy: Platelets >= 100,000/uL
    • For patients who DID receive induction chemotherapy: Platelets >= 75,000/uL
  • Hemoglobin >= 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb >= 8.0 g/dl is acceptable) (within 30 days prior to Step 1 registration)
  • Creatinine clearance > 50 mL/min estimated by Cockcroft-Gault formula (within 30 days prior to Step 1 registration)
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) (within 30 days prior to Step 1 registration)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x ULN (within 30 days prior to Step 1 registration)
  • Negative pregnancy test (serum or urine) within 14 days prior to Step 1 registration for women of child bearing potential
  • The patient or a legally authorized representative must provide study-specific informed consent prior to study entry

Exclusion Criteria:

  • Cervical esophageal cancers arisen from 15-18 cm from the incisors
  • Patients with T4b disease according to the AJCC 8th edition
  • Definitive clinical or radiologic evidence of metastatic disease
  • Any active malignancy within 2 years of study registration that may alter the course of esophageal cancer treatment
  • Prior thoracic radiotherapy that would result in overlap of radiation therapy fields
  • Severe, active co-morbidity defined as follows:

    • Active uncontrolled infection requiring IV antibiotics at the time of Step 1 registration
    • Symptomatic congestive heart failure, unstable angina, or cardiac arrhythmia not controlled by pacer device at the time of Step 1 registration
    • Myocardial infarction within 3 months prior to Step 1 registration
  • Pregnant and/or nursing females
  • Human immunodeficiency virus (HIV) positive with CD4 count < 200 cells/microliter. Note that patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count >= 200 cells/microliter within 30 days prior to registration. Note also that HIV testing is not required for eligibility for this protocol. This exclusion criterion is necessary because the treatments involved in this protocol may be significantly immunosuppressive
  • PRIOR TO STEP 2 REGISTRATION:
  • Unable to obtain confirmation of payment coverage (insurance or other) for either possible radiation treatment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03801876


Locations
Show Show 47 study locations
Sponsors and Collaborators
NRG Oncology
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Steven Lin NRG Oncology
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Responsible Party: NRG Oncology
ClinicalTrials.gov Identifier: NCT03801876    
Other Study ID Numbers: NRG-GI006
NCI-2018-03378 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
NRG-GI006 ( Other Identifier: NRG Oncology )
NRG-GI006 ( Other Identifier: CTEP )
U10CA180822 ( U.S. NIH Grant/Contract )
U10CA180868 ( U.S. NIH Grant/Contract )
First Posted: January 14, 2019    Key Record Dates
Last Update Posted: October 8, 2020
Last Verified: October 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Squamous Cell
Adenocarcinoma
Esophageal Neoplasms
Esophageal Squamous Cell Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Paclitaxel
Carboplatin
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action