Organ-Preserving Endoscopic Resection & Adjuvant RADIO-immuno-chemotherapy for Esophageal Cancer

NCT05667298 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: 10001
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to assess the safety of delivering concurrent adjuvant chemoradiation or immuno-radiation therapy after EMR/ESD in pT1b/T2N0 esophageal cancer patients. The main objectives of the study are:

1. 1.Assess the feasibility of enrolling 10 patients.
2. 2.Assess the safety of delivering concurrent adjuvant chemoradiation or immunoradiation therapy after EMR/ESD in pT1b/T2 esophageal cancer patients

Conditions

Esophageal Cancer

Outcome Measures

Primary Outcomes (2)

• Feasibility of enrolling 10 patients

  Assess the feasibility of enrolling 10 patients (i.e. Raw count of number of patients enrolled in 1.5 years)

  1.5 years

• Safety (proportion of patients developing Grade 3 or above adverse events)

  Assess the safety of delivering concurrent adjuvant chemoradiation or immunoradiation therapy after EMR/ESD in pT1b/T2 esophageal cancer patients. This will be done using CTCAE. This will be descriptive and be based on proportion of patients developing Grade 3 or above adverse events.

  1.5 years

Secondary Outcomes (2)

• Health-related quality of life (change in FACT-E score between pretreatment/baseline score to the score at the 2-year mark post-resection)

  2 years

• Progression-free survival

  2 years

Study Arms (2)

Adjuvant Immunoradiotherapy (ARM1) and Adjuvant Immunotherapy (ARM1B)

EXPERIMENTAL

The primary/preferred adjuvant therapy will be immunoradiotherapy (ARM1); however, if this combination is felt to be too high-risk for specific patients, the next preferred therapy will be immunotherapy without radiation (ARM1B).

Drug: Adjuvant Immunoradiotherapy (ARM1) and Adjuvant Immunotherapy (ARM1B)

Adjuvant chemoradiotherapy

EXPERIMENTAL

Some patients have medical conditions, i.e., severe auto-immune disease that prohibits them from receiving immunotherapy. In such patients, adjuvant therapy will be provided in the form of concurrent chemoradiotherapy (ARM2).

Drug: Adjuvant chemoradiotherapy

Interventions

Adjuvant Immunoradiotherapy (ARM1) and Adjuvant Immunotherapy (ARM1B) DRUG

Durvalumab treatment is to begin six weeks following patient ESD/EMR surgery. Patients may delay dosing under the following certain circumstances: 1. Dosing may be delayed per Toxicity Management Guidelines (Appendix IV), due to either an immune or a non-immune-related AE. 2. Dosing intervals of subsequent cycles may be shortened as clinically feasible in order to gradually align treatment cycles with the schedule of tumor efficacy (RECIST) and PRO assessments. Subsequent time between 2 consecutive doses cannot be less than 22 days, based on the half-lives of durvalumab (see current Investigator Brochure for durvalumab). 3. Standard of Care Arm (CROSS): 4. Patients may delay and subsequently resume dosing per local standard clinical practice. If dosing must be delayed for reasons other than treatment-related toxicity, dosing will occur as soon as feasible.

Adjuvant Immunoradiotherapy (ARM1) and Adjuvant Immunotherapy (ARM1B)

Adjuvant chemoradiotherapy DRUG

Durvalumab treatment is to begin six weeks following patient ESD/EMR surgery. Patients may delay dosing under the following certain circumstances: 1. Dosing may be delayed per Toxicity Management Guidelines (Appendix IV), due to either an immune or a non-immune-related AE. 2. Dosing intervals of subsequent cycles may be shortened as clinically feasible in order to gradually align treatment cycles with the schedule of tumor efficacy (RECIST) and PRO assessments. Subsequent time between 2 consecutive doses cannot be less than 22 days, based on the half-lives of durvalumab (see current Investigator Brochure for durvalumab). 3. Standard of Care Arm (CROSS): 4. Patients may delay and subsequently resume dosing per local standard clinical practice. If dosing must be delayed for reasons other than treatment-related toxicity, dosing will occur as soon as feasible.

Adjuvant chemoradiotherapy

Eligibility Criteria

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

You may qualify if:

• AGE \>18
• Able to provide informed consent.
• Pathological stage T1B or T2 esophageal or non-metastatic gastro-esophageal adenocarcinoma, squamous cell cancer or mixed histology.
• Ineligible for or declining esophagectomy.
• Completed endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD).
• Body weight \>30kg
• Adequate normal organ and marrow function as defined below:
• Haemoglobin ≥9.0 g/dL
• Absolute neutrophil count (ANC) ≥1.0 × 109 /L
• Platelet count ≥75 × 109/L
• Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). \<\<This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.\>\>
• AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤5x ULN
• Measured creatinine clearance (CL) \>40 mL/min or Calculated creatinine CL\>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:
• Males:
• Creatinine CL (mL/min) = Weight (kg) x (140 - Age) 72 x serum creatinine (mg/dL)

You may not qualify if:

• Participation in another clinical study with an investigational product during the last 4 weeks.
• Concurrent enrolment in another clinical study unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
• Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumour embolization, monoclonal antibodies) ≤15 days prior to the first dose of study drug. If sufficient wash-out time has not occurred due to the schedule or PK properties of an agent, a longer wash-out period will be required, as agreed by AstraZeneca and the investigator.
• Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia and vitiligo.
• Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
• Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study Physician.
• Any concurrent chemotherapy, investigative product (IP), biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
• Radiotherapy treatment to more than 30% of the bone marrow within 4 weeks of the first dose of study drug.
• Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of durvalumab. Note: Local surgery of isolated lesions for palliative intent is acceptable.
• History of allogenic organ transplantation.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia.
• Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement.
• Any chronic skin condition that does not require systemic therapy.
• Patients without active disease in the last 5 years may be included but only after consultation with the study physician.

Sponsors & Collaborators

• University of Manitoba: lead
• Manitoba Medical Service Foundation: collaborator
• CancerCare Manitoba: collaborator
• AstraZeneca: collaborator

Study Sites (1)

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

MeSH Terms

Conditions

Esophageal Neoplasms

Interventions

26S proteasome non-ATPase regulatory subunit 13; Chemoradiotherapy, Adjuvant

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)

Chemoradiotherapy; Combined Modality Therapy; Therapeutics; Drug Therapy; Radiotherapy

Study Officials

• Biniam Kidane

  University of Manitoba

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: The primary/preferred adjuvant therapy will be immunoradiotherapy (ARM1); however, if this combination is felt to be too high-risk for specific patients, the next preferred therapy will be immunotherapy without radiation (ARM1B). Some patients have medical conditions, i.e., severe auto-immune disease that prohibits them from receiving immunotherapy. In such patients, adjuvant therapy will be provided in the form of concurrent chemoradiotherapy (ARM2).

Study Record Dates

• First Submitted: October 6, 2022
• First Posted: December 28, 2022
• Study Start: March 1, 2023
• Primary Completion: July 1, 2025
• Study Completion (Estimated): July 1, 2029
• Last Updated: October 29, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)