Organ Preservation in Early Rectal Cancer Patients

NCT03548961 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: GI-11618-1013
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single arm phase II study of neoadjuvant chemotherapy followed by local excision and post-operative chemoradiotherapy in patients with early stage, low rectal adenocarcinoma. After completion of pre-treatment tests/procedures (including pelvic MRI/ERUS; MRI is mandatory at baseline and other imaging is encouraged) and confirmation of eligibility, systemic therapy with FOLFOX will be administered for 12 weeks. 2 to 4 weeks after the chemotherapy, restaging of the primary tumor will be done to evaluate response to therapy (Pelvic MRI and /or sigmoidoscopy). Patients with disease progression or inadequate response to chemotherapy to allow local excision will continue with evaluation and treatment per the current standard of care (chemoradiation followed by TME). These patients will be considered failures for the primary endpoint of the study. Patients who respond to the neoadjuvant chemotherapy will proceed with local excision (open, TEMS or TAMIS), 6-12 weeks after the completion of neoadjuvant chemotherapy, followed by 5-FU based chemoradiotherapy 4-12 weeks after local excision. Patients with positive margins at the time of local excision will also be treated as per standard of care and will be considered as failures. Number of patients who can undergo successful local excision with this approach will define the success of the strategy. After chemoradiation therapy post local excision, patients will be followed closely every 3 months for the first 3 years and then every 2 months for the next 2 years (history/physical, CEA and pelvic MRI). Patients who are deemed failures for the primary end-point will be followed as per standard of care, off-study.

Conditions

Rectal Cancer

Outcome Measures

Primary Outcomes (1)

• number of patients whose tumor can be resected by local excision with negative margins

  Patients who undergo neoadjuvant chemotherapy, and are able to achieve a local excision in early stage lower rectal adenocarcinoma with negative margins

  3 months

Secondary Outcomes (5)

• Number of patients with improved bowel function in patients treated with organ preserving approach for early stage low rectal cancer before and after therapy

  3 years

• Number of patients with improved sexual function treated with organ preserving approach for early stage low rectal cancer before and after therapy

  3 years

• Number of patients with improved health-related quality of life treated with organ preserving approach for early stage low rectal cancer before and after therapy

  3 years

• Overall survival (OS) of patients

  5 years

• Disease-free survival (DFS) of patients

  5 years

Study Arms (1)

Neoadjuvant chemotherapy

EXPERIMENTAL

Drug: FOLFOX regimen

Interventions

FOLFOX regimen DRUG

FOLFOX regimen will be administered for 6 cycles. Each cycle is 14 days followed by restaging, local surgery and concurrent chemo radiation therapy

Neoadjuvant chemotherapy

Eligibility Criteria

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

You may qualify if:

• Histologically proven adenocarcinoma of the lower rectum (lower border ≤6 cm from anal verge as assessed by pelvic MRI).
• Clinical stage T1N0, T2N0, T3N0; high risk T1 and low risk T3 stage patients are also allowed. Clinical staging should be estimated based on the combination of the following assessments: physical exam by the primary surgeon, CT Chest/Abdomen/Pelvis or PET/CT along with Pelvic MRI and Endoscopic Rectal Ultrasound (ERUS). If a pelvic MRI is performed, it is acceptable to perform CT of the chest/abdomen, omitting CT imaging of the pelvis.
• No prior therapy for rectal cancer
• Age \> 18 years.
• ECOG performance status 0 or 1
• Patients must have normal organ and marrow function as defined below
• Leukocytes \> 3,000/mcL
• Absolute neutrophil count \> 1,500/mcL
• Platelets \> 100,000/mcL
• Total bilirubin \< 1.5 times ULN
• AST/ALT (SGOT/SGPT) \< 3 times institutional normal limits
• Creatinine \< 1.5 times ULN OR
• Creatinine clearance \> 60 Ml/min/1.73 m2 for patients with creatinine levels above institutional normal
• Ability to understand and willingness to sign a written informed consent and HIPAA consent document

You may not qualify if:

• Patients with contraindication to use FOLFOX chemotherapy and pelvic radiation.
• Low risk T1 tumors that fulfill all of the following - size\<4 cm, lack of lymphovascular invasion and well differentiated histology, are excluded
• High risk T3 tumors that fulfill any of the following - circumferential tumor, extension into mesorectal fascia \> 5mm, prediction of positive circumferential resection margin, are also excluded.
• T4, node positive or advanced rectal adenocarcinoma. Node positivity defined as nodes greater than 1cm in short axis with loss of uniform cortex/fatty hilum
• Patients receiving other investigational agents
• Patients who have had chemotherapy (for other malignancies) within 3 years prior to registration
• Patients with any prior pelvic radiation therapy
• Prior malignancies requiring systemic therapy within the last 3 years (as prior therapy can increase toxicity of current chemo regimen, those patients should be excluded).
• History of allergic reactions attributed to compound of similar chemical or biologic composition to the agents used in this study
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Known HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with chemotherapeutic drugs. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy.
• Pregnant or breast feeding.

Sponsors & Collaborators

• Fox Chase Cancer Center: lead

Study Sites (1)

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Folfox protocol

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

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: May 25, 2018
• First Posted: June 7, 2018
• Study Start: May 11, 2018
• Primary Completion: April 23, 2024
• Study Completion (Estimated): March 1, 2027
• Last Updated: April 4, 2025

Record last verified: 2025-04

Locations

US (1)