Radiation Dose Intensification With Accelerated Hypofractionated Intensity Modulated Radiation Therapy and Concurrent Carboplatin and Paclitaxel for Inoperable Esophageal Cancer

NCT ID: NCT04046575

Last Updated: 2025-07-11

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-11-07
• Study Completion Date: 2029-11-20

Brief Summary

Rates of local disease control in patients with locally advanced esophageal cancer who are not candidates for surgical resection are suboptimal. Despite treatment with chemotherapy and radiation therapy approximately half of patients will develop recurrence of their cancer at the site of the original primary cancer. Salvage therapy options are largely ineffective and nearly all patients who develop local disease recurrence will succumb to their cancer. Recent clinical trials for lung cancer have demonstrated that local tumor control can be improved safely with accelerated hypofractionated radiation therapy regimens in order to achieve radiation dose intensification. This clinical trial aims to adapt those techniques and assess the safety of such a regimen for the treatment of inoperable thoracic esophageal cancers.

Conditions

Esophagus Cancer; Esophageal Cancer; Cancer of the Esophagus

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

IMRT + Carboplatin + Paclitaxel

Concurrent chemoradiation will consist of hypofractionated intensity modulated radiation therapy (IMRT) with simultaneous integrated boost (SIB) for 3 weeks with carboplatin and paclitaxel for 3 cycles every 7 days. Endoscopy and (optional) PET/CT within 6-8 weeks post-completion of chemoradiation.

Group Type: EXPERIMENTAL

Intensity Modulated Radiation Therapy

Intervention Type: RADIATION

-15 fractions of treatment

Carboplatin

Intervention Type: DRUG

Begins on day 1 of radiotherapy

MD Anderson Symptom Inventory (MDASI)-Plus module

Intervention Type: OTHER

The QOL questionnaires will be answered by the patients prior to the start of chemoradiation, on the last week of RT, and at 6-8 week follow-up, 3, 6, 9, and 12 months post completion of RT

EuroQol (EQ-5D)

Intervention Type: OTHER

The QOL questionnaires will be answered by the patients prior to the start of chemoradiation, on the last week of RT, and at 6-8 week follow-up, 3, 6, 9, and 12 months post completion of RT

SF-12

Intervention Type: OTHER

The QOL questionnaires will be answered by the patients prior to the start of chemoradiation, on the last week of RT, and at 6-8 week follow-up, 3, 6, 9, and 12 months post completion of RT

MOS Social Support Measure

Intervention Type: OTHER

The QOL questionnaires will be answered by the patients prior to the start of chemoradiation, on the last week of RT, and at 6-8 week follow-up, 3, 6, 9, and 12 months post completion of RT

CES-D

Intervention Type: OTHER

The QOL questionnaires will be answered by the patients prior to the start of chemoradiation, on the last week of RT, and at 6-8 week follow-up, 3, 6, 9, and 12 months post completion of RT

Blood for ctDNA (optional)

Intervention Type: PROCEDURE

-Collected at pre-treatment, every 2 weeks during chemoradiation, every 2-3 weeks during consolidation chemotherapy, completion of therapy, 6-8 week follow-up, 3 month follow-up, 6 month follow-up, and 12 month follow-up

Blood for SCCA

Intervention Type: PROCEDURE

-Collected at pre-treatment, completion of therapy, and 6 month follow-up

Paclitaxel

Intervention Type: DRUG

Begins on day 1 of radiotherapy

Interventions

Intensity Modulated Radiation Therapy

-15 fractions of treatment

Intervention Type: RADIATION

Carboplatin

Begins on day 1 of radiotherapy

Intervention Type: DRUG

MD Anderson Symptom Inventory (MDASI)-Plus module

The QOL questionnaires will be answered by the patients prior to the start of chemoradiation, on the last week of RT, and at 6-8 week follow-up, 3, 6, 9, and 12 months post completion of RT

Intervention Type: OTHER

EuroQol (EQ-5D)

The QOL questionnaires will be answered by the patients prior to the start of chemoradiation, on the last week of RT, and at 6-8 week follow-up, 3, 6, 9, and 12 months post completion of RT

Intervention Type: OTHER

SF-12

The QOL questionnaires will be answered by the patients prior to the start of chemoradiation, on the last week of RT, and at 6-8 week follow-up, 3, 6, 9, and 12 months post completion of RT

Intervention Type: OTHER

MOS Social Support Measure

The QOL questionnaires will be answered by the patients prior to the start of chemoradiation, on the last week of RT, and at 6-8 week follow-up, 3, 6, 9, and 12 months post completion of RT

Intervention Type: OTHER

CES-D

The QOL questionnaires will be answered by the patients prior to the start of chemoradiation, on the last week of RT, and at 6-8 week follow-up, 3, 6, 9, and 12 months post completion of RT

Intervention Type: OTHER

Blood for ctDNA (optional)

-Collected at pre-treatment, every 2 weeks during chemoradiation, every 2-3 weeks during consolidation chemotherapy, completion of therapy, 6-8 week follow-up, 3 month follow-up, 6 month follow-up, and 12 month follow-up

Intervention Type: PROCEDURE

Blood for SCCA

-Collected at pre-treatment, completion of therapy, and 6 month follow-up

Intervention Type: PROCEDURE

Paclitaxel

Begins on day 1 of radiotherapy

Intervention Type: DRUG

Other Intervention Names

IMRT; Paraplatin; Taxol

Eligibility Criteria

Inclusion Criteria

• Biopsy-proven carcinoma of the thoracic esophagus, or gastroesophageal junction (GEJ).
• Amenable to definitive chemoradiation.
• Unresectable esophageal cancer or not a surgical candidate as determined by a surgeon or multidisciplinary tumor board.
• At least 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Complete blood count (CBC) with differential obtained within 30 days prior to registration with adequate bone marrow function:

• Absolute neutrophil count (ANC) ≥1,500 cells/mm3
• Platelets ≥100,000 cells/ mm3
• Hemoglobin ≥9 g/dL (transfusion or other intervention to achieve hemoglobin ≥9 g/dL is acceptable).
• Adequate renal function within 30 days prior to registration: Serum creatinine ≤ 1.5x upper limit of normal or calculated creatinine clearance ≥ 50 mL/min within 30 days prior to registration estimated by the Cockcroft-Gault formula:

Creatinine Clearance (male) = [(140 - age) x (wt in kg)] [(Serum Creatinine mg/dl) x (72)] Creatinine Clearance (female) = 0.85 x Creatinine Clearance (male)

*Adequate hepatic function within 30 days prior to registration: bilirubin ≤ 1.5x upper limit of normal, ALT/AST ≤3 x upper limit of normal (ULN).

• Negative pregnancy test within 14 days of registration or otherwise be determined to not be of childbearing potential. Postmenopausal women must be amenorrheic for 12 months or more. Women of childbearing potential must agree to perform appropriate contraception methods and not breastfeed until 30 days after last chemotherapy.
• Planned to undergo IMRT with photon beam radiation therapy. 3D CRT and proton modalities are not allowed.
• Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Exclusion Criteria

• Primary cervical esophageal cancer
• Siewert-Stein Type III carcinomas of the stomach.
• Esophageal perforation, fistula, or deep ulceration to the mediastinum.
• Currently receiving any other investigational agents.
• Known brain metastases. Patients with known brain metastases must be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to carboplatin, paclitaxel, or other agents used in the study.
• Planning to undergo or has already undergone induction chemotherapy.
• Presence of any active malignancy within 2 years that may alter the course of esophageal cancer therapy.
• Prior radiation therapy to the neck, thorax, or abdomen is not allowed UNLESS there is expected to be no overlap with the study esophageal radiotherapy treatment. Prior radiation therapy treatment plan reports must be reviewed by study PI to verify no overlap of treatment fields.
• Severe active comorbidity as defined below:

• Unstable angina and/or congestive heart failure within the last 6 months.
• Transmural myocardial infarction within the last 6 months.
• History of stroke, cerebral vascular accident, or transient ischemic attack within the last 6 months.
• Serious and inadequately controlled cardiac arrhythmia
• Bacterial or fungal infection requiring intravenous antibiotics at the time of registration.
• Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration.
• Peripheral neuropathy > grade 1 at time of registration.
• Persistent complications from any major surgery within 4 weeks of study treatment start.
• Any other major medical illness that in the investigator's opinion would prevent safe administration or completion of protocol therapy.
• Pregnant or lactating woman. Women of childbearing potential with positive pregnancy test at baseline, or women who have not taken a pregnancy test at baseline. A man or woman who does not agree to use appropriate contraception.
• Patients with HIV are eligible unless their CD4+ T-cell counts are < 350 cells/mcL or they have a history of AIDS-defining opportunistic infection within the 12 months prior to registration. Concurrent treatment with effective ART according to DHHS treatment guidelines is recommended.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gregory Vlacich, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University School of Medicine

St Louis, Missouri, United States

Countries

United States

Related Links

http://www.siteman.wustl.edu

Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Other Identifiers

201909019

Identifier Type: -

Identifier Source: org_study_id