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

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

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.

Study Overview

• Status: Completed
• Conditions: Locally Advanced Rectal Cancer (LARC)
• Intervention / Treatment: Drug: nal-IRI; Procedure: Surgical resection; Drug: 5-FU/LV; Drug: Oxaliplatin; Other: Watch-and-wait

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Maranon
  • Madrid
    • Majadahonda, Madrid, Spain, 28022
      • Hospital Universitario Puerta de Hierro Majadahonda
    • Sanchinarro, Madrid, Spain, 28050
      • Hospital Universitario Madrid Sanchinarro

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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)

Collaborators and Investigators

• Sponsor: Fundación de investigación HM
• Collaborators: Syntax for Science, S.L
• Investigators: Study Director: Antonio Cubillo, MD, Director

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2019
• Primary Completion (Actual): October 21, 2022
• Study Completion (Actual): October 21, 2022

Study Registration Dates

• First Submitted: July 3, 2019
• First Submitted That Met QC Criteria: July 3, 2019
• First Posted (Actual): July 5, 2019

Study Record Updates

• Last Update Posted (Actual): December 13, 2022
• Last Update Submitted That Met QC Criteria: December 12, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms; Antineoplastic Agents; Oxaliplatin
• Other Study ID Numbers: HM-RE-2017-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No