A Study Involving Neoadjuvant Chemoradiotherapy With Hypofractionated Radiotherapy in Patients With Esophageal and Gastroesophageal Junction Adenocarcinoma

Phase II Study of Neoadjuvant Chemoradiotherapy With Hypofractionated Radiotherapy in Patients With Esophageal and Gastroesophageal Junction Adenocarcinoma

An open-label, single-centre, non-randomized, Phase II trial in patients with esophageal adenocarcinoma. This study aims to show that delivering hypofractionated neoadjuvant concurrent chemoradiotherapy is is equally effective as conventionally fractionated neoadjuvant concurrent chemoradiotherapy.

Study Overview

• Status: Recruiting
• Conditions: Esophageal Cancer
• Intervention / Treatment: Radiation: Hypofractionated radiotherapy

Detailed Description

Patients with carcinoma of the esophagus or gastroesophageal junction who are suitable for curative intent trimodality therapy will receive carboplatin (AUC 2) and paclitaxel (50 mg/m2) intravenously weekly for 5 weeks. External beam RT in 5 fractions over 1 week will be delivered any time between week 3-5 of chemotherapy. Ideally patients should get radiotherapy during week 3 of chemotherapy but delivery during week 4-5 is permissible with documentation of the minor deviation. RT must start within 30 calendar days of signing the informed consent form. While restaging imaging is done as per institutional guidelines, ideally patients should get a PET/CT 6 weeks post chemoradiotherapy. Patient will then go for esophagectomy 6-12 weeks after the completion of chemoradiotherapy, but ideally at 6-8 weeks post chemoradiotherapy. Patients will be assessed for acute toxicity weekly during neoadjuvant therapy and then biweekly until esophagectomy. One month after surgery, patient will have a final clinical follow up with the radiation oncologist and review any post-operative complications.

• Study Type: Interventional
• Enrollment (Estimated): 42
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Amy Abel; Phone Number: 403-476-2506; Email: amy.abel@albertahealthservices.ca
• Study Contact Backup: Name: Sanjune Laurence Lee, MD; Phone Number: 403-521-3164; Email: Sangjune.Lee@albertahealthservices.ca

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada
      • Recruiting
      • Tom Baker Cancer Centre
      • Contact: Sangjune Lee, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Biopsy-proven invasive adenocarcinoma of the esophagus or GEJ (Siewart type I-II)
2. Surgically resectable clinical stage T1N1-3 or T2-3N0-3 and no clinical evidence of metastatic spread are eligible (M0).
3. Maximum length (based on best information available, with EGD preferred) and width of the tumor as seen on CT not exceeding 8 cm and 5 cm respectively.
4. ECOG performance status ≤ 2
5. Patient able to begin radiation treatment within 30 calendar days of signing the informed consent form.
6. Age ≥ 18 and ≤ 75.

7. Adequate hematological, renal, hepatic and pulmonary function as defined by:

   1. Hemoglobin > 100 g/L
   2. Platelet count > 100x109/L
   3. Absolute neutrophil count > 1.5x109/L
   4. Total bilirubin ≤ 1.5x the upper limit of institutional normal
   5. Creatinine ≤ 120 µmol/L
   6. FEV1 ≥ 1.5 L
8. Patients capable of childbearing are using adequate contraception.
9. Written and informed consent of patient.

Exclusion Criteria:

1. Past or current history of malignancy other than entry diagnosis except for non-melanomatous skin cancer, or curatively treated carcinoma in situ of the cervix or a cured malignancy more than 5 years prior to enrollment
2. Previous chemotherapy and radiotherapy
3. New York heart Association Class III/IV and no history of active angina. Documented myocardial infarction within the 6 months preceding registration (pretreatment echocardiogram evidence of infarct only will not exclude patients). Patients with a history of significant ventricular arrhythmia requiring medication or congestive heart failure. History of 2nd or 3rd degree heart blocks
4. Pre-existing motor or sensory neurotoxicity greater than WHO grade 1
5. Active infection or other serious underlying medical condition which would impair the ability of the patient to receive the planned treatment
6. Dementia or altered mental status that would prohibit the understanding and giving of informed consent
7. Weight loss > 20% within 3 months of the date of screening
8. Esophageal stent
9. Pregnant or lactating patients; women of childbearing potential must have a negative serum pregnancy test within 7 days of Treatment Visit 1. Women or men of childbearing potential must use effective contraception (defined by the use of two birth control methods, which can be either two barrier methods or a barrier method plus a hormonal method to prevent pregnancy). Subjects must start using birth control from the time they have signed the Informed Consent Form prior to start of therapy until 120 days post completion of study therapy or study discontinuation, which must be documented in the eCRF.
10. Patients unfit for any treatment component, including absolute contraindications for radiotherapy or Connective Tissue Disease.
11. Unable to complete surveys in English without aid of interpreter.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hypofractionated neoadjuvant concurrent chemoradiotherapy; Drug: Carboplatin and Taxol (paclitaxel) Patients will receive carboplatin (AUC 2) and paclitaxel (50 mg/m2) intravenously for 5 weeks on Days 1,8,15,22 and 29. Radiation: Hypofractionated radiation	Radiation: Hypofractionated radiotherapy; Hypofractionated radiation 23 Gy in 5 fractions with a simultaneous integrated boost of 26 Gy in 5 fractions to the gross tumor volume (GTV) given concurrently over 1 week during week 3 of chemotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the efficacy of delivering 5-fraction hypofractionated chemoradiotherapy	Tumor regression grades and pathological complete response rates determined after one week of surgery	up to the Post-operative visit (60-90 days after surgery)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the rates of acute toxicities	Safety will be determined by recording adverse events as per the CTCAE classification and grading system	up to the Post-operative visit (60-90 days after surgery)
To compare pathological response rates to changes in tumor FDG-PET uptake	Changes in tumor FDG-PET standard uptake value and total lesion glycolysis	At the time of the re-staging scan (6 weeks post chemoradiotherapy).
To compare pathological response rates to changes in tumor dimensions	Changes in tumor dimensions on CT	At the time of the re-staging scan (6 weeks post chemoradiotherapy).
To compare pathological response rates to dysphagia scores	Change in dysphagia score, measured at Screening/Baseline and at the Post-operative clinical follow-up	up to the Post-operative visit (60-90 days after surgery)
Correlate pre- and post-chemoradiation immune microenvironment composition with the above outcome variables (pathological response, dysphagia scores, changes in FDG-PET uptake and/or tumor dimensions on CT)	Translational correlation between immune infiltration of biopsy and resection specimens with pathological (regression grades and response rates), clinical (dysphagia scores) and imaging (FDG-PET uptake and/or tumor dimensions on CT) outcomes	At the time of the re-staging scan (6 weeks post chemoradiotherapy).

Collaborators and Investigators

• Sponsor: AHS Cancer Control Alberta

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2023
• Primary Completion (Estimated): February 3, 2027
• Study Completion (Estimated): February 3, 2028

Study Registration Dates

• First Submitted: May 4, 2022
• First Submitted That Met QC Criteria: May 6, 2022
• First Posted (Actual): May 11, 2022

Study Record Updates

• Last Update Posted (Actual): January 11, 2024
• Last Update Submitted That Met QC Criteria: January 10, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma
• Other Study ID Numbers: NACEA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No