Neoadjuvant Therapy for Localized Rectal Adenocarcinoma

NCT04418895 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: LCCC 1933
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Rectal Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• complete pathologic response (pCR) rate

  Anatomic stage for rectal cancer uses the American Joint Committee on Cancer (AJCC) Tumor/Node/Metastasis (TNM) system, which is based on:Size of primary tumor (T) and whether it has grown into nearby areas. Spread to regional lymph nodes (N). Spread (metastasis; M) to other organs of the body. Once the T, N, and M categories have been determined, this information is combined into a prognostic group. Higher numbers mean the cancer is more advanced. Stage prefixes include "c" for clinical stage, "p" for pathological stage, and "y" to indicate that the clinical or pathologic classification has been determined after preoperative therapy Complete pathologic response is defined as no disease on pathology at resection (ypT0N0).

  At time of surgery (1- 26 weeks after completion of standard of care neoadjuvant treatment)

Secondary Outcomes (6)

• pathologic down staging rate

  At time of surgery (1-26 weeks after completion of standard of care neoadjuvant treatment)

• near pathological complete response (near-pCR) rate

  At time of surgery (1-26 weeks after completion of standard of care neoadjuvant treatment)

• R0 resection rate

  At time of surgery (1-26 weeks after completion of standard of care neoadjuvant treatment)

• Recurrence Free Survival (RFS) rate

  3 years after surgical resection

• Overall Survival (OS) rate

  3 years after surgical resection

Study Arms (1)

Single Arm: Standard of Care

EXPERIMENTAL

Investigator's choice of total neoadjuvant therapy (TNT) comprised of neoadjuvant chemotherapy and chemoradiation followed by surgical resection; or neoadjuvant chemoradiation followed by surgical resection and then adjuvant chemotherapy.

Other: Chemoradiation; Radiation: short course radiation therapy; Drug: mFOLFOX6; Drug: CAPOX; Drug: fluoropyrimidine +/- oxaliplatin

Interventions

Chemoradiation OTHER

Subjects will receive neoadjuvant chemoradiation per standard of care. This is typically comprised of radiotherapy of 5040 cGy (centigray) with concurrent capecitabine 825 mg/m2 by mouth (po) two times daily (bid) (typically rounded to the nearest 500 mg dose) or infusional 5-fluorouracil (5FU). However, dosing and administration are at the discretion of the treating medical and radiation oncologist.

Single Arm: Standard of Care

short course radiation therapy RADIATION

An acceptable alternative approach is short-course radiation therapy per standard of care, which is typically comprised of radiotherapy of 25 Gy (gray) in 5 fractions, with surgery within 1 week of completion of therapy or delayed for 6-8 weeks. Selection of the optimal radiation therapy approach is at the discretion of the treating medical oncologist, radiation oncologist, and surgical oncologist. However, generally, short-course radiation therapy is not recommended for low-lying tumors less than 5 centimeters (cm) from the anal verge.

Single Arm: Standard of Care

mFOLFOX6 DRUG

possible consolidative neo-adjuvant chemotherapy. This treatment is at the discretion of the treating medical oncologist, radiation oncologist, and surgical oncologist.

Also known as: leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin

Single Arm: Standard of Care

CAPOX DRUG

possible consolidative neo-adjuvant chemotherapy. This treatment is at the discretion of the treating medical oncologist, radiation oncologist, and surgical oncologist.

Also known as: Capecitabine, Oxaliplatin

Single Arm: Standard of Care

fluoropyrimidine +/- oxaliplatin DRUG

possible adjuvant chemotherapy regimen. Subjects who do not receive preoperative mFOLFOX6 or CAPOX typically receive postoperative adjuvant chemotherapy with a fluoropyrimidine +/- oxaliplatin for an additional 16-18 weeks of therapy, if permitted based on recovery after surgical resection and post-surgical performance status. This treatment is at the discretion of the treating medical oncologist. Subjects will remain on study regardless of postoperative therapy administration or duration.

Single Arm: Standard of Care

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Tumor staged as T3-4 or node-positive by pelvic MRI or endorectal ultrasound, or node-positive by CT scan; OR
• Tumor fixed to extra colonic structures as determined by digital rectal examination; OR
• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead

Study Sites (1)

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, 27599-7295, United States

Location

Related Links

• University of North Carolina Lineberger Comprehensive Cancer Center Clinical Trials

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Chemoradiotherapy; Leucovorin; Fluorouracil; Oxaliplatin; XELOX

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Drug Therapy; Radiotherapy; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals

Study Officials

• Michael S Lee, MD

  UNC Lineberger Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2020
• First Posted: June 5, 2020
• Study Start: August 13, 2021
• Primary Completion: May 1, 2022
• Study Completion: May 1, 2025
• Last Updated: November 10, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)