ChemoRadiation And Tislelizumab for Esophageal/EGJ Cancer (CRATER)

This study aims to determine the effects of chemoradiation and Tislelizumab on Esophageal/EGJ Cancer before and after surgery.

Study Overview

• Status: Withdrawn
• Conditions: Esophageal Cancer; Esophagogastric Junction Cancer
• Intervention / Treatment: Drug: Intravenous Tislelizumab; Drug: Chemotherapy; Radiation: Fractionated radiation; Procedure: Esophagectomy

Detailed Description

Esophageal cancer patients in this trial will receive chemoradiation therapy with tislelizumab, which is an anti-PD-1 antibody, before surgery. Patient will be evaluated for complete pathological response or major pathological response rate following chemoradiation. Patient will continue on to get tislelizumab after surgery to complete total of a year of treatment. They will be evaluated for PFS and OS. Throughout the study, drug tolerability and toxicities will be monitored.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University Of Kentucky

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Able to provide written informed consent and can understand and agree to comply with the requirements of the study and the schedule of assessments
2. Age ≥ 18 years but 80 years or younger on the day of signing the informed consent form.
3. Histologically proven esophageal squamous cell cancer or adenocarcinoma.
4. De novo diagnosis, have not received prior treatment
5. AJCC 8. T1N1 or T2-4aN0-2M0 resectable disease
6. ECOG Performance Status ≤ 1

7. Adequate organ function as indicated by the following laboratory values

   a. Patients must not have required a blood transfusion or growth factor support ≤ 14 days before sample collection at screening for the following i. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L ii. Platelets ≥ 100 x 109/L iii. Hemoglobin ≥ 90 g/L b. Serum creatinine ≤ 1.5 x ULN (upper limit of normal) or estimated Glomerular Filtration Rate ≥ 60 mL/min/1.73 m2 c. Serum total bilirubin ≤ 1.5 x ULN (total bilirubin must be < 3 x ULN for patients with Gilberts syndrome). d. AST and ALT ≤ 3 x ULN

8. Females of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study, and ≥ 120 days after the last dose of tislelizumab, and have a negative urine or serum pregnancy test ≤ 7 days before the first dose of tislelizumab.

9. Non-sterile males must be willing to use a highly effective method of birth control for the duration of the study and for ≥ 120 days after the last dose of tislelizumab

   Exclusion Criteria:

10. Unresectable disease either T4b or M1 per AJCC8
11. Deemed inoperable for any reason by attending surgeon
12. Any prior treatment directed at the tumor except biopsy.
13. Active autoimmune diseases such as SLE, RA requiring systemic immunosuppression or history of autoimmune diseases that may relapse.
14. Any active malignancy ≤ 2 years before first dose of study drug, except for cancer that has been treated curatively (e.g., resected basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast)

15. Any condition that required systemic treatment with either corticosteroids (> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication ≤ 14 days before tislelizumab. Note: Patients who are currently or have previously been on any of the following steroid regimens are not excluded:

    1. Adrenal replacement steroid (dose ≤ 15 mg daily of prednisone or equivalent)
    2. Topical, ocular, intra-articular, intranasal, or inhaled corticosteroid with minimal systemic absorption
    3. Short course (≤ 7 days) of corticosteroid prescribed prophylactically (e.g., for contrast dye allergy) or for the treatment of a non-autoimmune condition (e.g., delayed-type hypersensitivity reaction caused by contact allergen)
16. Laboratory test abnormalities in potassium, sodium, or corrected calcium > Grade 1 despite standard medical management
17. History of interstitial lung disease, non-infectious pneumonitis or uncontrolled diseases including pulmonary fibrosis, acute lung diseases, etc.
18. Severe chronic or active infections requiring systemic antibacterial, antifungal or antiviral therapy, including tuberculosis infection, etc.
19. A known history of HIV infection not controlled with anti-retroviral therapy
20. Patients with untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers whose HBV DNA is > 500 IU/mL or patients with active hepatitis C virus (HCV) should be excluded. Note: Inactive hepatitis B surface antigen (HBsAg) carriers, treated and stable hepatitis B (HBV DNA < 500 IU/mL), and cured hepatitis C patients can be enrolled
21. Prior allogeneic stem cell transplantation or organ transplantation

22. Any of the following cardiovascular risk factors:

    1. Cardiac chest pain, defined as moderate pain that limits instrumental activities of daily living, ≤ 28 days before first dose of tislelizumab and chemotherapy
    2. Any history of heart failure meeting New York Heart Association (NYHA) Classification III or IV (Appendix 6) ≤ 6 months
    3. Any event of ventricular arrhythmia ≥ Grade 2 in severity ≤ 6 months prior to initiation of treatment on study.
23. A history of severe hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
24. Has received radiation therapy within 4 weeks, chemotherapy, immunotherapy (e.g., interleukin, interferon, thymosin), or any investigational therapies within 14 days or 5 half lives (whichever is shorter) of the first study drug administration

25. Was administered a live vaccine ≤ 4 weeks before tislelizumab Note: Seasonal vaccines for influenza are generally inactivated vaccines and are allowed.

    Intranasal vaccines are live vaccines and are not allowed. The mRNA vaccine for SARSCoV2 is allowed if the second dose is administered two weeks before study drug is administered.

26. Underlying medical conditions (including laboratory abnormalities) or alcohol or drug abuse or dependence that, will be unfavorable for the administration of study drug or affect the explanation of drug toxicity or AEs or result in insufficient or might impair compliance with study conduct.
27. Concurrent participation in another therapeutic clinical study.
28. History of allergy to platinum or taxane
29. Li-Fraumeni Syndrome where radiation is contraindicated

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: All patient; All patients receive Tislelizumab, q3week; chemotherapy with carboplatin and paclitaxel weekly concurrently for 5 weeks before surgery. Tislelizumab is continued q3week in all patients after surgery for a total of one year from the start of study.

Drug: Intravenous Tislelizumab; Participants will receive 200mg, every three weeks for up to 51 weeks; Other Names: immunotherapy; Drug: Chemotherapy; Carboplatin (AUC2) and Paclitaxel (50mg/m2), Weekly x 5 weeks; Other Names: carboplatin and paclitaxel; Radiation: Fractionated radiation; Concurrent with chemo, x5 weeks; Procedure: Esophagectomy; Surgical resection of cancer after chemoradiation therapy when no disease progression found.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological complete response rate (pCR)	Pathological complete response (pCR) rate in patients treated with tislelizumab and chemoradiation followed by surgery. The pCR rate will be estimated by number of patients who has had pCR divided by the total number of evaluable patients treated with neoadjuvant therapy before surgery. The exact 95% confidence interval of the pCR rate will be provided.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS)	The time from the participants' date of surgery to the date of disease progression or death, whichever occurs first	12 months
Major pathological response (MPR)	The number of patients who had 90% or more tumor showing necrosis divided by the total number of evaluable patients treated with neoadjuvant therapy before surgery	12 months

Collaborators and Investigators

• Sponsor: Zhonglin Hao
• Collaborators: University of Kentucky; BeiGene
• Investigators: Principal Investigator: Zhonglin Hao, MD, PhD, University Of Kentucky

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): April 1, 2022
• Primary Completion (ANTICIPATED): March 1, 2023
• Study Completion (ANTICIPATED): December 1, 2033

Study Registration Dates

• First Submitted: February 8, 2022
• First Submitted That Met QC Criteria: February 8, 2022
• First Posted (ACTUAL): February 18, 2022

Study Record Updates

• Last Update Posted (ACTUAL): November 8, 2022
• Last Update Submitted That Met QC Criteria: November 4, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Carboplatin; Paclitaxel
• Other Study ID Numbers: MCC-21-LUN-125-PMC

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