Short-course Radiotherapy With Induction and Consolidation Chemotherapy in Patients With Locally Advanced Rectal Cancer (SHORT-ICAR)

Phase II Study of Short-course Radiotherapy With Induction and Consolidation Chemotherapy in Patients With Locally Advanced High-risk Rectal Cancer

Short-course radiotherapy followed by consolidation chemotherapy has shown a better response rate when compared to chemoradiotherapy treatment.

In addition, recent studies have shown better tolerance with total neoadjuvant treatment, with induction or consolidation chemotherapy. Induction chemotherapy could reduce the size of the tumor, treat micrometastases early and allow treatment to start immediately (avoiding potential delays in waiting for radiotherapy). While consolidation chemotherapy allows longer waiting times for surgery, with higher response rates.

Study Overview

• Status: Unknown
• Conditions: Rectal Cancer; Total Neoadjuvant Treatment
• Intervention / Treatment: Other: Approach

Detailed Description

Methods: This trial aim to evaluate induction treatment with CAPOX, followed by short-course radiotherapy consolidation chemotherapy with CAPOX. After 5-7 weeks, patients will be evaluate by MRI. Patients with incomplete clinical response will be referred to immediate surgery and patients with complete clinical response will be managed with "watch and wait" approach. Patients with progression disease during the treatment phase will be withdrawn from the study and will receive their treatment according to the investigator's judgment.

The sample size was calculated according to Simon's optimal two-stage design. Accordingly, 21 patients must be included in each group during the first stage and 24 during the second stage. Treatment regimen will be considered effective if 9 or more patients show good response (final analysis), reaching 80% power with an alpha of 0.10 level of significance.

• Study Type: Interventional
• Enrollment (Anticipated): 54
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Juliana Souza; Phone Number: 5521988734435; Email: juominelli@hotmail.com
• Study Contact Backup: Name: Isabele Small; Phone Number: 00552132076666; Email: ismall@inca.gov.br

Study Locations

• Brazil
  • Rio de Janeiro, Brazil, 20231-050
    • Recruiting
    • INCA- Instituto Nacional de Câncer
    • Contact: Luana Cerva; Phone Number: 00552132076666; Email: luana.cerva@inca.gov.br
    • Principal Investigator: Juliana O Souza, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically confirmed adenocarcinoma of mid or low rectum
• Locally advanced rectal cancer with one of the high-risk factors confirmed by high-resolution thin-slice Magnetic resonance image (3 mm) tumors extending to within 1 mm of, or beyond the mesorectal fascia; tumor extending 5 mm or more into perirectal fat; resectable cT4 tumors; lower third; nodal involvement; extramural vascular invasion
• ECOG performance status of 0-2
• An informed consent has been signed by the patient

Exclusion Criteria:

• Upper rectal cancer
• Metastatic disease
• The patient received any previous therapy for colorectal cancer or another malignancy
• Other malignant tumours within the last 5 years except cervical carcinoma in situ and basal cell carcinoma of the skin
• Previous thromboembolic or haemorrhagic events within 6 months prior to registration
• Patients with malabsorption syndrome or difficulties in swallowing
• The patient has severe underlying diseases or poor condition to receive chemotherapy or radiotherapy
• Pregnant of breastfeeding women
• The patient who participate in another clinical trial, or receives any drug for the trial
• Uncontrolled peripheral neuropathy (more than grade 2)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Experimental; Patients will receive 2 CAPOX cycles, followed by short-course radiotherapy and 4 CAPOX cycles.	Other: Approach; Patients will receive 2 CAPOX cycles, followed by short-course radiotherapy and 4 CAPOX cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate MRI good response rate after the total neoadjuvant treatment	Good response rate is defined as the proportion of patients who reached mrTRG 1 or 2 and the absence of remote disease in the reevaluation period, with the denominator being the total number of patients who started total neoadjuvant treatment.	16-20 weeks after SCRT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free survival in 3 years	defined as the time from the date of MRI of the pelvis of the reassessment period to relapse, death or last contact date.	3 years
Overall survival	defined as the time from the date of the induction chemotherapy until the death or date of last contact	3 years
Describe the safety and tolerability of total neoadjuvant treatment.	Incidence of adverse events (AEs), serious AEs, deaths and laboratory abnormalities in participants who received at least one dose of study treatment	1 year

Collaborators and Investigators

• Sponsor: Instituto Nacional de Cancer, Brazil
• Investigators: Principal Investigator: Juliana Souza, Instituto Nacional de Cancer, Brazil

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 10, 2020
• Primary Completion (ANTICIPATED): June 1, 2022
• Study Completion (ANTICIPATED): June 1, 2022

Study Registration Dates

• First Submitted: December 14, 2020
• First Submitted That Met QC Criteria: December 14, 2020
• First Posted (ACTUAL): December 19, 2020

Study Record Updates

• Last Update Posted (ACTUAL): December 19, 2020
• Last Update Submitted That Met QC Criteria: December 14, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: rectal cancer
• 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
• Other Study ID Numbers: SHORT-ICAR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No