Clinical trial NCT05943210: The Radiation Oncology-Biology Integration Network (ROBIN) Molecular Characterization Trial (MCT) of Standard Short Course Radiotherapy for Rectal Cancer
Official title: The Radiation Oncology-Biology Integration Network (ROBIN) Molecular Characterization Trial (MCT) of Standard Short Course Radiotherapy for Rectal Cancer.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Rectal Cancer
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2023-07-13
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is a molecular characterization trial (MCT) of 25 consecutively treated rectal cancers with short-course radiotherapy (scRT; 25Gy/5 fractions). Tissue and imaging will be collected at three time-points: 1. Baseline (day -28 to 0) - pelvic MRI and CT, research biopsy, blood (50ml), stool. 2. After 5 RT fractions (day 5-10) - CT, research biopsy, blood (50ml), stool 3. At time of surgery (wk 6) - MRI and CT, surgical tumor and nodal specimens, blood (50ml), stool.
Primary purpose: BASIC_SCIENCE

Brief summary: This trial (molecular characterization trial) focuses on rectal cancer, a common cancer that is treated with radiotherapy (RT) as standard of care and represents a setting in which to study the effects of RT on the immune system.

Detailed description: The study aims to test the hypothesis that the radiation therapy will assist in targeting the rectal cancer by mounting a robust immune response against the rectal cancer.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed diagnosis of adenocarcinoma of the rectum
* Age ≥ 18 years
* ECOG performance status 0-1
* cT2-T3N0 or cT1-3N1
* Rectal cancer amenable to total mesorectal excision
* No evidence of distant metastases
* No prior pelvic radiation therapy
* No prior chemotherapy or surgery for rectal cancer
* No infections requiring systemic antibiotic treatment
* Hgb \>8.0 gm/dL, PLT \> 150,000/mm3, total bilirubin ≤ 1.5x upper limit of normal, AST ≤ upper limit of normal, ALT ≤ 3x upper limit of normal
* Patients must read, agree to, and sign a statement of informed consent prior to participation in this study. Patients who do not read or understand English or eligible but must have the consent form read to them in its entirety by an official translator. Informed consent for non-literate or non-English speaking patients may not be obtained by using a relative or a member of the patient's clinical team as a translator.
* Female participants or reproductive potential, defined as not surgically sterilized and between menarche and 1 year post menopause, must have a negative serum pregnancy test within 4 weeks prior to initiation of study treatment.
* Women with childbearing potential who are negative for pregnancy (urine or blood) and who agree to use effective contraceptive methods. A woman of childbearing potential is defined by one who is biologically capable of becoming pregnant. Reliable contraception should be used from trial screening and must be continued throughout the study.

Exclusion Criteria:

* Recurrent rectal cancer
* Primary unresectable rectal cancer is defined as a primary rectal tumor which, on the basis of either physical exam or pelvic MRI, is deemed to be adherent or fixed to adjacent pelvic structures (en bloc resection will not be achieved with negative margins).
* cT4 will be excluded.
* ≥4 regional lymph nodes each ≥10 mm on pelvic MRI
* Patients who have received prior pelvic radiotherapy
* Patients with prior allogenic stem cell or solid organ transplantation.
* Patients receiving treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and antitumor necrosis factor-α agents) administered at \>10 mg/day prednisone or equivalent within 2 weeks prior to initiation of study treatment.
* Patients with any other concurrent medical or psychiatric condition or disease which, in the investigator's judgment would make them inappropriate candidates for entry into this study
* Patients receiving other anticancer or experimental therapy. No other experimental therapies (including chemotherapy, radiation, hormonal treatment, antibody therapy, immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors, matrix metalloprotease inhibitors, thalidomide, anti-VEGF/Flk-1 monoclonal antibody, or other experimental drugs) of any kind are permitted while the patient is receiving study treatment.
* Women who are pregnant or breastfeeding. Women of childbearing potential who are unwilling or unable to use an acceptable method of birth control to avoid pregnancy for the entire study period and for up to four weeks after the study.

Primary outcomes:
measure: Number of tissue biopsies obtained from treated patients
timeFrame: Baseline
measure: Number of tissue biopsies obtained from treated patients
timeFrame: Week 1
measure: Number of tissue biopsies obtained from treated patients
timeFrame: Week 6
measure: Number of research specimens obtained before RT.
timeFrame: Baseline
measure: Number of research specimens obtained after RT.
timeFrame: Week 1
measure: Number of research specimens obtained at the time of surgery.
timeFrame: Week 6
Secondary outcomes:
measure: Changes in tumor morphology from pre-treatment and post-treatment MRI will be measured.
timeFrame: Baseline, Week 1
measure: Changes in tumor morphology from pre-treatment and post-treatment CT will be measured.
timeFrame: Baseline, Week 1
measure: Changes in tumor texture from pre-treatment and post-treatment MRI will be measured.
timeFrame: Baseline, Week 1
measure: Changes in tumor texture from pre-treatment and post-treatment CT will be measured.
timeFrame: Baseline, Week 1
measure: Changes in enhancement kinetics from pre-treatment and post-treatment MRI will be measured.
timeFrame: Baseline, Week 1
measure: Changes in enhancement kinetics from pre-treatment and post-treatment CT will be measured.
timeFrame: Baseline, Week 1
measure: Changes in functional diffusion patterns from pre-treatment and post-treatment MRI will be measured.
timeFrame: Baseline, Week 1
measure: Changes in functional diffusion patterns from pre-treatment and post-treatment CT will be measured.
timeFrame: Baseline, Week 1
measure: Changes in Cellular stress (quantification of reactive Oxygen species (ROS))
timeFrame: Baseline, Week 1, Week 6
measure: Changes in immunological fitness related to radio-responsiveness and their associated pathological response will be measured by quantifying senescence using vital dye DDAO.
timeFrame: Baseline, Week 1, Week 6
measure: Changes in immunological fitness related to radio-responsiveness and their associated pathological response will be measured by quantifying aging using p16 protein expression as a marker.
timeFrame: Baseline, Week 1, Week 6
measure: Changes in immunological fitness related to radio-responsiveness and their associated pathological response will be measured by quantifying gamma-H2aX (aging).
timeFrame: Baseline, Week 1, Week 6
measure: Comparing levels of cell death related to radio responsiveness will be measured by quantifying cleaved caspase-3
timeFrame: Baseline, Week 1, Week 6
Other outcomes:
Locations:
city: Chicago
country: United States
facility: The University of Chicago
state: Illinois
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Brooklyn
country: United States
facility: New York Presbyterian Brooklyn Methodist Hospital
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital - Queens
state: New York
Study officials:
affiliation: Weill Medical College of Cornell University
name: Silvia Formenti, M.D.
role: STUDY_CHAIR
affiliation: Weill Medical College of Cornell University
name: Encouse Golden, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: