Organ Preservation in Early Rectal Cancer Patients

NCT ID: NCT03548961

Last Updated: 2025-04-04

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-05-11
• Study Completion Date: 2027-03-01

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Neoadjuvant chemotherapy

Group Type: EXPERIMENTAL

FOLFOX regimen

Intervention Type: DRUG

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

Interventions

FOLFOX regimen

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Histologically proven adenocarcinoma of the lower rectum (lower border ≤6 cm from anal verge as assessed by pelvic MRI).

2. 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.

3. No prior therapy for rectal cancer

4. Age > 18 years.

5. ECOG performance status 0 or 1

6. 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

7. Ability to understand and willingness to sign a written informed consent and HIPAA consent document

Exclusion Criteria

1. Patients with contraindication to use FOLFOX chemotherapy and pelvic radiation.

2. Low risk T1 tumors that fulfill all of the following - size<4 cm, lack of lymphovascular invasion and well differentiated histology, are excluded

3. 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.

4. 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

5. Patients receiving other investigational agents

6. Patients who have had chemotherapy (for other malignancies) within 3 years prior to registration

7. Patients with any prior pelvic radiation therapy

8. 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).

9. History of allergic reactions attributed to compound of similar chemical or biologic composition to the agents used in this study

10. 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.

11. 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.

12. Pregnant or breast feeding.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fox Chase Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Countries

United States

Other Identifiers

18-1013

Identifier Type: OTHER

Identifier Source: secondary_id

GI-116

Identifier Type: -

Identifier Source: org_study_id