Improving treatment for inoperable esophageal cancer with advanced radiation and chemotherapy

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

This study is testing a new combination of advanced radiation and chemotherapy to see if it can help people with inoperable esophageal cancer control their disease better and reduce the chances of it coming back.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Washington University School of Medicine (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 1 site (Saint Louis, Missouri)
• Trial ID: NCT04046575 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates a new treatment approach for patients with inoperable thoracic esophageal cancer by using accelerated hypofractionated intensity-modulated radiation therapy combined with chemotherapy agents carboplatin and paclitaxel. The goal is to enhance local disease control and reduce the recurrence of cancer at the original site. Participants will receive a regimen designed to intensify radiation doses safely, based on successful strategies previously used in lung cancer treatment. The study aims to assess the safety and effectiveness of this innovative treatment method.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with biopsy-proven unresectable thoracic esophageal cancer or gastroesophageal junction cancer.

Not a fit: Patients with resectable esophageal cancer or those with severe comorbidities that prevent them from undergoing chemoradiation may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve local control of esophageal cancer and potentially extend survival for patients who are not surgical candidates.

How similar studies have performed: Previous studies in lung cancer have shown success with similar accelerated radiation techniques, suggesting potential for this approach in esophageal cancer.

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.

Where this trial is running

Saint Louis, Missouri

• Washington University School of Medicine — Saint Louis, Missouri, United States (Recruiting)

Study contacts

• Principal investigator: Gregory Vlacich, M.D., Ph.D. — Washington University School of Medicine
• Study coordinator: Gregory Vlacich, M.D., Ph.D.

Conditions Esophagus Cancer; Esophageal Cancer; Cancer of the Esophagus