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.

Overview

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.

Interventions

• Radiation Short Course Radiation Therapy (scRT)
  Eligible patients will receive short course radiation therapy (scRT) of 25Gy over 5 days (fractions) for their localized rectal cancer. Research bloods stool and tissue will be collected at three time points: Baseline, end of radiation therapy and at surgery.
• Procedure Total Mesenteric Excision (TME)
  Subjects are expected to undergo total mesenteric Excision(TME) even if subjects have achieved complete response by imaging.TME is a specific surgical technique used in the treatment of rectal cancer in which the bowel with the tumor is entirely removed along with surrounding fat and lymph nodes.

Primary outcome measures

• Number of tissue biopsies obtained from treated patients [Time frame: Baseline]
• Number of tissue biopsies obtained from treated patients [Time frame: Week 1]
• Number of tissue biopsies obtained from treated patients [Time frame: Week 6]
• Number of research specimens obtained before RT. [Time frame: Baseline]
• Number of research specimens obtained after RT. [Time frame: Week 1]
• Number of research specimens obtained at the time of surgery. [Time frame: Week 6]

Secondary outcome measures (12)

• Changes in tumor morphology from pre-treatment and post-treatment MRI will be measured. [Time frame: Baseline, Week 1]
• Changes in tumor morphology from pre-treatment and post-treatment CT will be measured. [Time frame: Baseline, Week 1]
• Changes in tumor texture from pre-treatment and post-treatment MRI will be measured. [Time frame: Baseline, Week 1]
• Changes in tumor texture from pre-treatment and post-treatment CT will be measured. [Time frame: Baseline, Week 1]
• Changes in enhancement kinetics from pre-treatment and post-treatment MRI will be measured. [Time frame: Baseline, Week 1]
• Changes in enhancement kinetics from pre-treatment and post-treatment CT will be measured. [Time frame: Baseline, Week 1]
• Changes in functional diffusion patterns from pre-treatment and post-treatment MRI will be measured. [Time frame: Baseline, Week 1]
• Changes in functional diffusion patterns from pre-treatment and post-treatment CT will be measured. [Time frame: Baseline, Week 1]
• Changes in Cellular stress (quantification of reactive Oxygen species (ROS)) [Time frame: Baseline, Week 1, Week 6]
• Changes in immunological fitness related to radio-responsiveness and their associated pathological response will be measured by quantifying senescence using vital dye DDAO. [Time frame: Baseline, Week 1, Week 6]
• 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. [Time frame: Baseline, Week 1, Week 6]
• Changes in immunological fitness related to radio-responsiveness and their associated pathological response will be measured by quantifying gamma-H2aX (aging). [Time frame: Baseline, Week 1, Week 6]

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 or cT4 or cN2
• 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
• Total neoadjuvant therapy (short course radiotherapy followed by consolidative chemotherapy) is allowed
• 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).
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Basic science

Study locations

United States · 5 centers

• The University of Chicago — Chicago
• Rutgers Cancer Institute of New Jersey — New Brunswick
• New York Presbyterian Brooklyn Methodist Hospital — Brooklyn
• Weill Cornell Medical College — New York
• New York Presbyterian Hospital - Queens — New York

Identifiers

NCT: NCT05943210 · 22-08025121 · 1U54CA274291

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗