A Randomized Clinical trial comparing FOLFOX to CP chemotherapy regimens with addition of immunotherapy in the neoadjuvant chemoradiotherapy treatment of esophageal cancer based on complete pathological/clinical response in PET scan or surgery
Determination of response rate in FOLFOX7 and CP regimens based on surgical pathology report or PET scan report
Design
Randomized,non-blind, phase 2 clinical trial with parallel groups on 98 patients. The sealed envelope site was used for randomization.
Settings and conduct
This trial is conducted in the radio-oncology clinic of IKHC. Since the drugs are provided by the patients and during the treatment there is a need to monitor the side effects in each group so that the dosage of the drugs can be adjusted, the study is non-blind.
Participants/Inclusion and exclusion criteria
Patients with cancer of middle and lower thoracic esophagus and GEJ up to Sievert 2 with squamous cell pathology or adenocarcinoma
Intervention groups
Patients are divided into two groups. In both groups, patients undergo RT with a dose of 41.4 Gy in 23 sessions. Radiation therapy is performed five days a week and once a day. In group A, patients receive mFOLFOX 7 chemotherapy regimen simultaneously with RT every two weeks; While group B patients are treated weekly with CP regimen. The start of chemotherapy in both groups is on the first day of RT, which is repeated with the mentioned intervals. Both groups receive two doses of pembrolizumab immunotherapy two weeks after the end of CCRT with three-week intervals. Finally, patients undergo endoscopy and PET scan 8-10 weeks after the end of CRT, and according to the results, if there is a complete response to the treatment, they will be followed up (without surgery) and if there is no complete response to the treatment, they will undergo surgery.
Main outcome variables
Tumor location according to the EUS report
Pathological grade based on pathology report
Depth of penetration according to EUS
Lymph node according to EUS
Response to treatment based on PET scan and endoscopy report at week 8-10 after termination of treatment or surgical pathology report if performed
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20240701062297N1
Registration date:2024-07-07, 1403/04/17
Registration timing:prospective
Last update:2024-07-07, 1403/04/17
Update count:0
Registration date
2024-07-07, 1403/04/17
Registrant information
Name
Ali Aqamolaei
Name of organization / entity
Country
Iran (Islamic Republic of)
Phone
+98 34 3251 3424
Email address
ali.a1374a@gmail.com
Recruitment status
recruiting
Funding source
Expected recruitment start date
2024-09-22, 1403/07/01
Expected recruitment end date
2026-09-23, 1405/07/01
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
A Randomized Clinical trial comparing FOLFOX to CP chemotherapy regimens with addition of immunotherapy in the neoadjuvant chemoradiotherapy treatment of esophageal cancer based on complete pathological/clinical response in PET scan or surgery
Public title
Evaluation of preferred chemotherapy regimen during esophageal cancer radiotherapy
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
ECOG Functional Status 0 & 1
EUS and PET/CT for local staging and evaluation of locoregional staging and distant metastasis
Adenocarcinoma or SCC of middle and lower thoracic esophagus including GEJ with Sivert 1 and 2 (from 25 cm from the incisor to the end of the cardia)
T1N1-3M0 or T2-4N0-3M0 cancer stages based on EUS and PET/CT. All affected areas (tumor and lymph nodes) in all patients should be operable (surgically respectable) and placed in radiotherapy fields.
The maximum length of the tumor is 10 cm
Proper liver, renal and blood function as follows: Number of granulocytes ≥ 1500 per μl Platelet count ≥ 100,000 per μl Bilirubin ≤ 1.5 times the maximum normal value (ULN) Liver enzymes AST and ALT ≤ 2.5 times the maximum normal value Creatinine clearance ≥ 60 (according to Cockcroft and Gault formula)
Men and women of childbearing age should use sperm and ovum preservation techniques before starting treatment. Sexually active women of childbearing age should use contraceptives during treatment.
Obtaining Informed Consent
Exclusion criteria:
Primary tumor in the cervical and upper thoracic esophagus (15 to 25 cm from the anterior tooth according to the endoscopic report)
Presence of distant metastasis on initial CT or PET
Stage T4b or tracheobronchial fistula on EUS
The presence of a supraclavicular pathological lymph node while the primary tumor is located in the middle or lower esophagus.
Pathology of SCC with celiac node involvement
Positive cytology in diagnostic laparoscopy
Adenocarcinoma pathology with dMMR reporting
The presence of a stent in the esophagus
History of chemotherapy or radiation therapy ofthe mediastinum and upper abdomen
The existence of contraindications for receiving 5-fluorouracil, taxane and platinum drugs
Pregnancy and breastfeeding
Autoimmune diseases (lupus, multiple sclerosis, etc.)
Uncontrolled or insulin-treated diabetes
Severe underlying neuropathy
Age
From 18 years old to 75 years old
Gender
Both
Phase
2
Groups that have been masked
No information
Sample size
Target sample size:
98
Randomization (investigator's opinion)
Randomized
Randomization description
Eligible patients will be randomly divided into two groups A and B with equal probability (1:1). The method of dividing the patients between these two groups is according to permuted block randomization with 4 blocks (25 blocks of 4 with 2 people in group A and 2 people in group B, where the sequence of people in each group is determined by the software).
Blinding (investigator's opinion)
Not blinded
Blinding description
Placebo
Not used
Assignment
Parallel
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Research ethics committees of school of medicine- Tehran university of medical sciences
Street address
Qods Ave, Keshavarz Blvd
City
Tehran
Province
Tehran
Postal code
1417653761
Approval date
2024-07-01, 1403/04/11
Ethics committee reference number
IR.TUMS.MEDICINE.REC.1403.150
Health conditions studied
1
Description of health condition studied
esophageal cancer
ICD-10 code
C15
ICD-10 code description
Malignant neoplasm of esophagus
Primary outcomes
1
Description
Response to treatment
Timepoint
at week 8-10 after termination of treatment
Method of measurement
based on PET scan and endoscopy report or surgical pathology report if performed
Secondary outcomes
empty
Intervention groups
1
Description
Intervention group: Receiving the mFOLFOX7 chemotherapy regimen during radiotherapy. In this group, patients undergo radiation therapy (RT) with a dose of 41.4 Gy in 23 sessions (1.8 Gy per session). Radiation therapy is performed five days a week (every day except Thursday and Friday) and once a day. In this group, patients receive mFOLFOX 7 chemotherapy regimen simultaneously with RT every two weeks. The start of chemotherapy in both groups is on the first day of RT, which is repeated with the mentioned intervals. Chemotherapy should be injected as soon as possible before radiation therapy and at least with an interval of two hours, and if it is not possible before radiation therapy, it can be injected as soon as possible after radiation therapy. Two weeks after the end of CRT, patients receive two doses of pembrolizumab immunotherapy with three-week intervals. All chemotherapy drugs are prepared and injected in Sadaf Clinic of Imam Khomeini Hospital Complex according to the protocol on the same day. mFOLFOX 7 regimen; 3 times every 2 weeks on days 1, 15 and 29 including: Oxaliplatin with a dose of 270 mg/m2 in people over 60 years old and a dose of 85 mg/m2 in people under 60 years old; injection on day 1, 5-fluorouracil (FU) as an infusion at a dose of 2400 mg/m2 over two days through a port-connected infusion pump; injection on the first day, leucovorin (LV) with a dose of 400 mg/m2; injection on the first day, pembrolizumab with a dose of 200 mg; Two injections, two weeks after the end of CRT, three weeks apart
Category
Treatment - Drugs
2
Description
Control group: Receiving the CP chemotherapy regimen during radiotherapy. In this group, patients undergo radiation therapy (RT) with a dose of 41.4 Gy in 23 sessions (1.8 Gy per session). Radiation therapy is performed five days a week (every day except Thursday and Friday) and once a day. In this group, patients receive CP chemotherapy regimen simultaneously with RT every two weeks. The start of chemotherapy in both groups is on the first day of RT, which is repeated with the mentioned intervals. Chemotherapy should be injected as soon as possible before radiation therapy and at least with an interval of two hours, and if it is not possible before radiation therapy, it can be injected as soon as possible after radiation therapy. Two weeks after the end of CRT, patients receive two doses of pembrolizumab immunotherapy with three-week intervals. All chemotherapy drugs are prepared and injected in Sadaf Clinic of Imam Khomeini Hospital Complex according to the protocol on the same day. CP regimen; 5 sessions every week on days 1, 8, 15, 22, 29 including Carboplatin with a dose of 2x AUC (The value of AUC is equal to GFR+25, which GFR is calculated according to the Cockcroft and Gault formula); Injection on the first day, Paclitaxel at a dose of 50 mg/m2; First day injection, Pembrolizumab with a dose of 200 mg; Two injections, two weeks after the end of CRT, three weeks apart
Category
Treatment - Drugs
Recruitment centers
1
Recruitment center
Name of recruitment center
Imam Khomeini Hospital Complex
Full name of responsible person
Ali Aqamolaei
Street address
Qarib Ave, Keshavarz Blvd, IKHC
City
Tehran
Province
Tehran
Postal code
۱۴۱۹۷۳۳۱۴۱
Phone
+98 21 6119 2601
Email
Imamhospital@tums.ac.ir
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Reza Ghaletaki
Street address
Qods Ave, Keshavarz Blvd, IKHC
City
tehran
Province
Tehran
Postal code
۱۴۱۹۷۳۳۱۴۱
Phone
+98 21 6119 2601
Email
rezaght@gmail.com
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Tehran University of Medical Sciences
Proportion provided by this source
100
Public or private sector
Public
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Academic
Person responsible for general inquiries
Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Ali Aqamolaei
Position
Resident
Latest degree
Medical doctor
Other areas of specialty/work
Radiotherapy
Street address
No 34, Tabatabaei Alley, North Kargar Ave
City
Tehran
Province
Tehran
Postal code
1418835954
Phone
+98 34 3251 3424
Fax
Email
ali.a1374a@gmail.com
Person responsible for scientific inquiries
Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Ali Aqamolaei
Position
Resident
Latest degree
Medical doctor
Other areas of specialty/work
Radiotherapy
Street address
No 34, Tabatabaei Alley, North Kargar Ave
City
Tehran
Province
Tehran
Postal code
1418835954
Phone
+98 34 3251 3424
Fax
Email
ali.a1374a@gmail.com
Person responsible for updating data
Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Ali Aqamolaei
Position
Resident
Latest degree
Medical doctor
Other areas of specialty/work
Radiotherapy
Street address
No 34, Tabatabaei Alley, North Kargar Ave
City
Tehran
Province
Tehran
Postal code
1418835954
Phone
+98 34 3251 3424
Fax
Email
ali.a1374a@gmail.com
Sharing plan
Deidentified Individual Participant Data Set (IPD)
Yes - There is a plan to make this available
Study Protocol
Yes - There is a plan to make this available
Statistical Analysis Plan
Not applicable
Informed Consent Form
Yes - There is a plan to make this available
Clinical Study Report
Yes - There is a plan to make this available
Analytic Code
Not applicable
Data Dictionary
Not applicable
Title and more details about the data/document
The dermographic information of the patients, their disease stage, the rate of response to treatment in each group and their differences are published in the final text of the article/thesis.
When the data will become available and for how long
At the time of article publication
To whom data/document is available
It should be decided on a case-by-case basis
Under which criteria data/document could be used
It should be decided on a case-by-case basis
From where data/document is obtainable
Imam Khomeini Hospital Complex, Cancer Institute, Department of Radio-Oncology
What processes are involved for a request to access data/document
After referring and reviewing the reason for the request, it can be used within 2 weeks if the principal researcher agrees and sees fit