A Study to Evaluate a Chemotherapy Treatment Followed by Chemo and Radiotherapy in Patients With Rectal Cancer

Study Overview
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Brief Summary
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This is an exploratory, open-label, single arm, non-randomized, multicenter, phase II clinical trial to determine the efficacy and clinical complete response rate in patients with rectal cancer and tumor preoperative evaluation after NAC (Neoadjuvant Chemotherapy) with NALIRINOX (5-FU [fluorouracil)/LV [Leucovorin calcium] + oxaliplatin + nal-IRI [Liposomal Irinotecan]) and chemoradiotherapy.

Official Title
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Phase II, Multicenter, Open-label, Non-randomized Study of Neoadjuvant Chemotherapy NALIRINOX (5-FU/LV + Oxaliplatin + Nal-IRI) Followed by Chemoradiotherapy in Patients With Rectal Cancer in a Watch-and-wait Program

Conditions
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Locally Advanced Rectal Cancer (LARC)

Intervention / Treatment
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* Drug: nal-IRI
* Procedure: Surgical resection
* Other: Watch-and-wait
* Drug: 5-FU/LV
* Drug: Oxaliplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or females, aged ≥ 18 years. Agree to participate and sign voluntary written ICF (Informed Consent Form) before any study specific procedure. Patients with confirmed histopathological diagnosis of rectal cancer. Patients with locally advanced rectal cancer T3-T4N0M0 or TxN+M0 and selected T2N0M0 candidates to watch & wait program. Patients considered for neoadjuvant treatment according to usual clinical practice may also be potential candidates. ECOG (Eastern Cooperative Oncology Grou)vperformance status 0 or 1. Patients who can receive radiotherapy and chemotherapy. No prior or concurrent malignant disease unless in complete remission for more than three years, except for adequately treated in situ carcinoma of the cervix, basal or squamous skin cell carcinoma or in situ transitional bladder cell carcinoma. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test before study entry. Both women and men must agree to use a highly effective contraceptive measure throughout the treatment period and for six months after discontinuation of treatment. Adequate hematologic function: hemoglobin ≥ 9g/dL; WBC (white blood cell count ) ≥ 4000/mm 3 ; neutrophils ≥ 1.5x10 9 /L; platelets ≥ 100x10 9 /L. Adequate hepatic function: total bilirubin ≤ 1.5xULN; ALT / AST (Alanine aminotransferase / Aspartate aminotransferase) ≤ 2.5xULN (Upper Limit of Normality) alkaline phosphatase ≤ 3xULN. Adequate renal function: creatinine ≤ 1xULN; creatinine clearance ≥ 60ml/min. No peripheral neuropathy (< Grade 2) No known history of dihydropyrimidine dehydrogenase deficiency (DPD) Exclusion Criteria: Patients with ECOG performance status ≥ 2. Stage I (T1N0M0) or stage IV (TxNxM1) AJCC (American Joint Committee on Cancer) rectal cancer. Any illness that the investigator considers will substantially increase the risk if the patient participates in the study. Pregnant or breast-feeding woman. Chronically active hepatitis B or C virus infection. Active uncontrolled infection. History, within last year, or presence of unstable angina, myocardial infarction, symptomatic congestive heart failure or asymptomatic left ventricular ejection fraction < 50% (assessed by multiple-gated acquisition scan or equivalent by ultrasound) or clinically significant valvular heart disease. Peripheral neuropathy (> Grade 1) Known history of dihydropyrimidine dehydrogenase deficiency (DPD) Known or suspected reactions to any component of the study medication (5-FU, leucovorin, irinotecan or oxaliplatin) or to components of similar chemical or biologic composition. Any phycological, familiar, sociological or geographical condition potentially hampering compliance with the study protocol or follow-up schedule. Concurrent participation in any other clinical trial likely to interfere with the therapeutic schedule. Patients that had received any previous treatment for their rectal cancer (surgery, chemotherapy or radiotherapy).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chemotherapy + Surgery<br>Treatment with 5-FU/LV + Oxaliplatin + nal-IRI for 8 cycles followed by standard chemoradiation (5 weeks) and surgical resection | Drug: nal-IRI<br>* Treatment with 5-FU/LV + Oxaliplatin + nal-IRI for 8 cycles followed by standard chemoradiation (5 weeks)<br>Procedure: Surgical resection<br>* Surgical resection of the tumour<br>Drug: 5-FU/LV<br>* Treatment with 5-FU/LV + Oxaliplatin + nal-IRI for 8 cycles followed by standard chemoradiation (5 weeks)<br>Drug: Oxaliplatin<br>* Treatment with 5-FU/LV + Oxaliplatin + nal-IRI for 8 cycles followed by standard chemoradiation (5 weeks)<br>|
| Experimental: Chemotherapy + Watch-and-wait<br>Treatment with 5-FU/LV + Oxaliplatin + nal-IRI for 8 cycles followed by standard chemoradiation (5 weeks) and watch-and-wait surveillance protocol. | Drug: nal-IRI<br>* Treatment with 5-FU/LV + Oxaliplatin + nal-IRI for 8 cycles followed by standard chemoradiation (5 weeks)<br>Other: Watch-and-wait<br>* No surgery approach<br>Drug: 5-FU/LV<br>* Treatment with 5-FU/LV + Oxaliplatin + nal-IRI for 8 cycles followed by standard chemoradiation (5 weeks)<br>Drug: Oxaliplatin<br>* Treatment with 5-FU/LV + Oxaliplatin + nal-IRI for 8 cycles followed by standard chemoradiation (5 weeks)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cCR (clinical complete response) rate in LARC ( locally advanced rectal cancer ) patients treated with chemo - chemoradiation. |  | expected 8 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | Through the study completion (estimated to be 15 months) | 
| Relapse-free survival |  | Through the study completion (estimated to be 15 months) | 
| Disease-free survival |  | Through the study completion (estimated to be 15 months) | 
| Percentage of patients that follow the watch-and-wait surveillance protocol |  | Through the study completion (estimated to be 15 months) | 
| Overall toxicity | acute and late toxicity of neoadjuvant treatment (chemo and chemoradiotherapy) according to the Common Toxicity Criteria (CTC) for adverse events (AE) | Through the study completion (estimated to be 15 months) |