Total Neoadjuvant Treatment Without Surgery For Locally Advanced Rectal Cancer

NCT03565029 | Completed Phase 2 DMC

• 1 other identifier: 2017-003671-60
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

NO-CUT is a one-stage phase II trial seeking to establish whether an oxaliplatin-based chemotherapy preceding standard neo-adjuvant fluoropyrimidines-based chemo radiotherapy, can safely spare demolitive surgical intervention in patients with operable rectal cancer, without increasing the risk of distant relapse. The trial also has a translational component aimed at establishing whether selected genomic, epigenetic, and transcriptomic markers are predictive of tumor and patient outcome.

Conditions

Colo-rectal Cancer

Keywords

rectal cancer; neoadjuvant; non operative management

Outcome Measures

Primary Outcomes (1)

• Distant Relapse-Free Survival (DRFS)

  Disease free survival rate

  2.5 years

Secondary Outcomes (5)

• Clinical complete response rate

  2 months

• Local recurrence and organ preservation rate

  6 months

• Colostomy-free survival

  6 months

• Overall survival

  2.5 years

• Patient reported outcomes

  2.5 years

Study Arms (1)

Medium/low locally advanced rectal cancer

EXPERIMENTAL

Patients with Stage II (cT3-4 N0) or Stage III (cT1-4, N1-3) locally advanced rectal cancer amenable to Total Mesorectal Excision (TME)/Abdominal-Perineal Amputation

Drug: XELOX; Radiation: Radiotherapy

Interventions

XELOX DRUG

Capecitabine and Oxaliplatin (4x cycles)

Medium/low locally advanced rectal cancer

Radiotherapy RADIATION

Pelvic radiotherapy

Medium/low locally advanced rectal cancer

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed diagnosis of adenocarcinoma of the medium/lower rectum
• Patients must have Stage II (cT3-4 N0) or Stage III (cT1-4, N1-3) tumor
• Locally advanced rectal cancer amenable to Total Mesorectal Excision (TME)/Abdominal-Perineal Amputation
• No evidence of distant metastases by chest, abdomen, and pelvis contrast enhanced CT scan (TC-positron emission computed tomography (PET) Whole Body (WB) is acceptable alternative in patient allergic to iodate contrast medium)
• No prior pelvic radiation therapy
• No prior oncologic medical therapy or surgery for rectal cancer
• Age \>18 years
• No infections requiring systemic antibiotic treatment
• Performance status 0-1 (ECOG Scale)
• absolute neutrophil count (ANC) \> 1.5 cell/mm3, Hb\>8.0 g/ dL, Platelet Count (PLT)\>150,000/mm3, total bilirubin \< or equal or 1.5 x upper limit of normal, Aspartate Aminotransferase (AST) \< or equal to three times upper limit of normal, Alanine Aminotransferase (ALT)\< or equal to three times upper limit of normal; Serum creatinine level \< or equal to 1.5 times the upper limit of normal
• Patients must read, agree to, and sign a statement of Informed Consent prior to participation
• Women with childbearing potential who are negative for pregnancy test (urine or blood) and who agree to use effective contraceptive methods
• Male subjects must also agree to use effective contraception

You may not qualify if:

• Recurrent rectal cancer
• Patients with a history of any arterial thrombotic event within the past 6 months, including angina (stable or unstable), MI, or CVA
• Intolerance or contraindication to Magnetic Resonance (MR) procedure
• Patients with any other concurrent medical or psychiatric condition
• Gastro-intestinal abnormalities, inability to take oral medication, any condition affecting absorption
• Patients with a history of a prior malignancy within the past 5 years, except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer.
• Patients with a history of thrombotic episodes, such as deep venous thrombosis, pulmonary embolus, Myocardial Infarction (MI) or cerebral vascular accident (CVA) occurring more than 6 months prior to enrollment may be considered for protocol participation, provided they are on stable doses of anticoagulant therapy. Patients who are anticoagulated for atrial fibrillation or other conditions may participate, provided they are on stable doses of anticoagulant therapy.
• Patients receiving other anticancer or experimental therapy.

Sponsors & Collaborators

• Niguarda Hospital: lead

Study Sites (1)

ASST GOM Niguarda

Milan, 20162, Italy

Location

MeSH Terms

Conditions

Colonic Neoplasms; Rectal Neoplasms

Interventions

XELOX; Radiotherapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Therapeutics

Study Design

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

Model Details: one-stage phase II trial seeking to establish whether an oxaliplatin-based chemotherapy preceding standard neo-adjuvant fluoropyrimidines-based chemo radiotherapy, can safely spare demolitive surgical intervention in patients with operable rectal cancer, without increasing the risk of distant relapse. The trial also has a translational component aimed at establishing whether selected genomic, epigenetic, and transcriptomic markers are predictive of tumor and patient outcome.

Study Record Dates

• First Submitted: June 8, 2018
• First Posted: June 21, 2018
• Study Start: June 1, 2018
• Primary Completion: October 31, 2022
• Study Completion: December 20, 2023
• Last Updated: December 27, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Weekly

Locations

IT (1)