Neoadjuvant Therapy for Localized Rectal Adenocarcinoma

• Status: Withdrawn
• Trial end date: 2025-05-01
• Target enrollment: 0
• Participant gender: All

Summary

This study is a prospective, single-arm, single-center study of investigator's choice of total neoadjuvant therapy (TNT) or neoadjuvant chemoradiation in locally advanced rectal cancer. The standard of care for rectal adenocarcinomas that are triiodothyronine-thyroxine (T3-T4) or node positive has generally been comprised of neoadjuvant chemoradiation, followed by surgical resection and then adjuvant chemotherapy. More recently, TNT, comprised of neoadjuvant chemotherapy and chemoradiation followed by surgical resection, has been increasingly used as a standard therapy approach. While the use of TNT is increasingly common, prospective study of outcomes following TNT has been limited. Moreover, there are not any biomarkers known at this time that impact clinical decision-making or personalization of therapy in the treatment of rectal cancer. In this study, we will collect pre-treatment rectal adenocarcinoma specimens and determine clinical outcome, including pathologic complete response rate, post-treatment pathologic downstaging rate, recurrence-free survival (RFS), overall survival (OS) and neoadjuvant rectal score, among patients who are treated with standard neoadjuvant chemoradiation or TNT, with an aim to investigate how baseline biomarkers and changes in biomarkers with standard therapies may be associated with, and modulate, clinical outcomes.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: UNC Lineberger Comprehensive Cancer Center
• Treatments: Capecitabine; Fluorouracil; Leucovorin; Levoleucovorin; Oxaliplatin

Criteria

Inclusion Criteria:

• Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information.

• Age ≥ 18 years at the time of consent.

• ECOG (Eastern Cooperative Oncology Group) Performance Status of 0-2 (See Appendix A. ECOG Performance Status Scale).

• Histological or cytological confirmation of rectal adenocarcinoma.

• Planned to receive treatment with neoadjuvant therapy, comprised of either 1) chemoradiation with concurrent fluoropyrimidine or short-course radiotherapy, or 2) total neoadjuvant therapy with fluoropyrimidine +oxaliplatin followed by chemoradiation or short-course radiotherapy. Rectal adenocarcinoma patients deemed candidates for neoadjuvant therapy include:

1. Tumor staged as T3-4 or node-positive by pelvic MRI or endorectal ultrasound, or node-positive by CT scan; OR

2. Tumor fixed to extra colonic structures as determined by digital rectal examination; OR

3. Tumor < 5 cm from sphincter mechanism.

• Willing and able to undergo baseline rectal tumor biopsy, and willing and able to donate blood for research purposes.

• Females of childbearing potential must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 12 weeks after treatment discontinuation. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method or an intrauterine device that meets <1% failure rate for protection from pregnancy in the product label.

• Male subjects with female partners must have had a prior vasectomy or agree to use an adequate method of contraception (i.e., double barrier method: condom plus spermicidal agent) starting with the first dose of study therapy through 12 weeks after the last dose of study therapy.

• Subjects are willing and able to comply with study procedures based on the judgement of the investigator or protocol designee.

Exclusion Criteria:

• Patients with colon carcinomas that are too proximal to receive neoadjuvant therapy per routine clinical practice (i.e. with primary tumor proximal to or at the sigmoid colon).

• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).

• Has a known additional malignancy that is active and/or progressive and is requiring treatment; exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, or other cancer for which the subject Is not currently receiving anti-cancer therapy such as chemotherapy, radiation therapy, targeted therapy, immunotherapy, or hormonal therapy.

• Patients who are not candidates at the discretion of their treating physicians to receive neoadjuvant chemoradiation or total neoadjuvant therapy (e.g. poor performance status, significant comorbidities, clinically significant organ dysfunction).