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

NCT04046575 | Active Not Recruiting Phase 1 DMC FDA Drug FDA Device

• 1 other identifier: 201909019
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD) of hypofractionated IMRT with chemotherapy

  The MTD of the combination of radiation and FOLFOX will be estimated using the proposed TITE-CRM model. After the phase I study, the MTD will be chosen as the dose that yields a posterior toxicity estimate closest to 20% while being between 15% and 25%. Toxicity will be coded using CTCAE v5.0.

  Through 6 month follow-up for all enrolled patients (estimated to be 65 months)

Secondary Outcomes (9)

• Median local relapse-free survival

  Through completion of follow-up (up to 6 years)

• Median overall survival

  Through completion of follow-up (up to 6 years)

• Median progression-free survival

  Through completion of follow-up (up to 6 years)

• Patient reported outcomes as measured by the MDASI-Plus

  From baseline through 12 months post end of treatment

• Patient reported outcomes as measured by the EQ-5D

  From baseline through 12 months post end of treatment

Study Arms (1)

IMRT + Carboplatin + Paclitaxel

EXPERIMENTAL

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.

Radiation: Intensity Modulated Radiation Therapy; Drug: Carboplatin; Other: MD Anderson Symptom Inventory (MDASI)-Plus module; Other: EuroQol (EQ-5D); Other: SF-12; Other: MOS Social Support Measure; Other: CES-D; Procedure: Blood for ctDNA (optional); Procedure: Blood for SCCA; Drug: Paclitaxel

Interventions

Intensity Modulated Radiation Therapy RADIATION

-15 fractions of treatment

Also known as: IMRT

IMRT + Carboplatin + Paclitaxel

Carboplatin DRUG

Begins on day 1 of radiotherapy

Also known as: Paraplatin

IMRT + Carboplatin + Paclitaxel

MD Anderson Symptom Inventory (MDASI)-Plus module 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

IMRT + Carboplatin + Paclitaxel

EuroQol (EQ-5D) 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

IMRT + Carboplatin + Paclitaxel

SF-12 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

IMRT + Carboplatin + Paclitaxel

MOS Social Support Measure 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

IMRT + Carboplatin + Paclitaxel

CES-D 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

IMRT + Carboplatin + Paclitaxel

Blood for ctDNA (optional) 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

IMRT + Carboplatin + Paclitaxel

Blood for SCCA PROCEDURE

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

IMRT + Carboplatin + Paclitaxel

Paclitaxel DRUG

Begins on day 1 of radiotherapy

Also known as: Taxol

IMRT + Carboplatin + Paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

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

MeSH Terms

Conditions

Esophageal Neoplasms

Interventions

Radiotherapy, Intensity-Modulated; Carboplatin; Blood Specimen Collection; Circulating Tumor DNA; squamous cell carcinoma-related antigen; Paclitaxel

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics; Coordination Complexes; Organic Chemicals; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Cell-Free Nucleic Acids; Nucleic Acids; Nucleic Acids, Nucleotides, and Nucleosides; DNA, Neoplasm; DNA; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Gregory Vlacich, M.D., Ph.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2019
• First Posted: August 6, 2019
• Study Start: November 7, 2019
• Primary Completion: June 2, 2025
• Study Completion (Estimated): November 20, 2029
• Last Updated: July 11, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)